Publications by authors named "Yingmei Wang"

136 Publications

Endometrial cancer in Lynch syndrome.

Int J Cancer 2021 Aug 16. Epub 2021 Aug 16.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33763DOI Listing
August 2021

Some Pleomorphic Adenomas of the Breast Share PLAG1 Rearrangements with the Analogous Tumor of the Salivary Glands.

Histopathology 2021 Jul 22. Epub 2021 Jul 22.

Department of Pathology, the Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, Shaan Xi Province, 710032, China.

Aims: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathologic features of our breast PAs and perform molecular analysis.

Methods: Seven cases of breast PA including two cases of carcinoma ex PA were analyzed. PLAG1 and HMGA2 gene rearrangements were assayed by FISH and RNA-Seq, respectively. RT-PCR and Sanger sequencing were used to verify RNA sequencing results.

Results: All seven cases of breast PA occurred in women. The histological features were similar to the analogous tumor in salivary glands, including a dual epithelial-myoepithelial component and negativity of ER, PR, and HER2 by immunohistochemistry. Of the two cases with carcinoma ex PA, one demonstrated minimal invasion and one was extensively invasive. PLAG1 rearrangements were identified in two cases (28.6%), but no rearrangements of HMG2A were found. A novel fusion product in PAs, TRPS1-PLAG1, was identified in one case. No patients had recurrence or metastasis with a follow-up period of 6 to 158 months.

Conclusions: Breast PA is rare, but it is an important differential diagnosis of breast pathology with the potential to develop carcinoma ex PA. We reported a novel TRPS1-PLAG1 fusion gene in breast PA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14461DOI Listing
July 2021

Weight Loss Improves Pregnancy and Livebirth Outcomes in Young Women with Early-Stage Endometrial Cancer and Atypical Hyperplasia.

Cancer Manag Res 2021 14;13:5711-5722. Epub 2021 Jul 14.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key laboratory of Female Reproductive Health and Eugenics, Tianjin, People's Republic of China.

Purpose: To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy.

Patients And Methods: Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors.

Results: Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63±12.03 and 67.08±8.18 kg, respectively, 27.06±4.44 and 25.73±3.15 kg/m, respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00-34.50), and the median relative weight loss was 6.70% (1.00-36.00%) over a median of 12 months (5.00-97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, =0.000; 64.00% vs 31.58%, =0.033); weight loss ≥5% significantly increased pregnancy and live birth rate in patients with BMI ≥25 kg/m. The risk ratio of weight loss ≥5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, =0.041).

Conclusion: Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥5% increased pregnancy and livebirth rates significantly in overweight and obese women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S316040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286730PMC
July 2021

IK: A novel cell mitosis regulator that contributes to carcinogenesis.

Cell Biochem Funct 2021 Jul 11. Epub 2021 Jul 11.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

Carcinogenesis is characterized by abnormal regulation of cell growth and cell death. IK is a novel cell mitosis regulator that may contribute to carcinogenesis. Previous studies showed that the loss of IK expression resulted in cell mitotic arrest and even cell death. Besides, IK can also inhibit the interferon gamma (IFN-γ)-induced expression of human leukocyte antigen (HLA) class II antigen, which is associated with tumour immune microenvironment. To gain insight into the current research progress regarding IK, we conducted a review and searched the limited literature on IK using PubMed or Web of Science. In this review, we discussed the possible biological functions and mechanisms of IK in cancer and its immune microenvironment. Future perspectives of IK were also mentioned to explore its clinical significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbf.3660DOI Listing
July 2021

Tumor Immune Microenvironment Components and Checkpoint Molecules in Anaplastic Variant of Diffuse Large B-Cell Lymphoma.

Front Oncol 2021 16;11:638154. Epub 2021 Jun 16.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Air Force Medical University, Xi'an, China.

Background: Anaplastic diffuse large B-cell lymphoma(A-DLBCL) is a rare morphological subtype characterized by the presence of polygonal, bizarre-shaped tumor cells. Our previous research found that A-DLBCL displays many genetic alterations and biological features that differ greatly from those of ordinary DLBCL. However, the status of tumor immune microenvironment components and checkpoint molecules in A-DLBCL remains unclear.

Methods: Thirty A-DLBCL patients were enrolled to study tumor immune microenvironment components and checkpoint molecules and their associations with clinicopathological features and prognosis.

Results: Patients with A-DLBCL presented higher expression of PD-L1 (40% 10%, P=0.004) than patients with ordinary DLBCL. FISH analysis showed that extra copies of PD-L1 were more frequent in A-DLBCL cases than in ordinary DLBCL cases (23.3% 4.0%, P=0.001). The numbers of PD-1 TILs (tumor infiltrating lymphocytes) and CD8T cells were significantly lower in A-DLBCL versus ordinary DLBCL. In contrast, the numbers of GATA3 Th2 cells, FOXP3 Tregs and CD33 myeloid-derived suppressor cells (MDSCs) were significantly higher in A-DLBCL than in ordinary DLBCL. The associations between clinicopathological features and tumor immune microenvironment cell frequency were analyzed in A-DLBCL patients. Briefly, the number of PD-1 TILs was lower and the number of CD33 MDSCs was higher in patients with mutated compared to those with wild-type . The number of FOXP3 Tregs was much lower in patients with a noncomplete response (CR) to chemotherapy than in those with a complete response. The number of CD8 T cells showed a decreasing trend in patients with high International Prognostic Index (IPI) scores and in those with concurrent MYC and BCL2 and/or BCL6 abnormalities. Univariate survival analysis showed that patients with PD-L1, mPD-L1(PD-L1 nonmalignant stromal cells) or mPD-L1 status had a significantly poorer overall survival (OS) than those with PD-L1 status. An increase in the number of CD3 T cells, FOXP3 Treg cells and T-bet Th1 cells was significantly associated with prolonged OS in patients with A-DLBCL.

Conclusion: Our study suggests that A-DLBCL displays a distinct pattern of tumor immune microenvironment components and checkpoint molecules that distinguish it from ordinary DLBCL. The analysis of tumor immune microenvironment components and checkpoint molecules could help in predicting the prognosis of A-DLBCL patients and determining therapeutic strategies targeting the tumor immune microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.638154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242181PMC
June 2021

Disruption of Jmjd3/p16 Signaling Pathway Causes Bizarre Parosteal Osteochondromatous Proliferation (BPOP)-like Lesion in Mice.

J Bone Miner Res 2021 Jun 25. Epub 2021 Jun 25.

Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare benign osteochondromatous lesion. At present, the molecular etiology of BPOP remains unclear. JMJD3(KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. Previously, Jmjd3 was shown to be critical for bone development and osteoarthritis. Here, we report that conditional deletion of Jmjd3 in chondrogenic cells unexpectedly resulted in BPOP-like lesion in mice. Biochemical investigations revealed that Jmjd3 inhibited BPOP-like lesion through p16 . Immunohistochemistry and RT-qPCR assays indicated JMJD3 and p16 level were significantly reduced in human BPOP lesion compared with normal subjects. This was further confirmed by Jmjd3/Ink4a double-gene knockout mice experiments. Therefore, our results indicated the pathway of Jmjd3/p16 may be essential for the development of BPOP in human. © 2021 American Society for Bone and Mineral Research (ASBMR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4401DOI Listing
June 2021

Inactivating Mutations of the Gene Weaken Ku80/Ku70-Mediated DNA Repair and Sensitize Endometrial Cancer to Chemotherapy.

Cancers (Basel) 2021 May 20;13(10). Epub 2021 May 20.

Department of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA.

IK is a mitotic factor that promotes cell cycle progression. Our previous investigation of 271 endometrial cancer (EC) samples from the Cancer Genome Atlas (TCGA) dataset showed IK somatic mutations were enriched in a cluster of patients with high-grade and high-stage cancers, and this group had longer survival. This study provides insight into how IK somatic mutations contribute to EC pathophysiology. We analyzed the somatic mutational landscape of IK gene in 547 EC patients using expanded TCGA dataset. Co-immunoprecipitation and mass spectrometry were used to identify protein interactions. In vitro and in vivo experiments were used to evaluate IK's role in EC. The patients with IK-inactivating mutations had longer survival during 10-year follow-up. Frameshift and stop-gain were common mutations and were associated with decreased IK expression. IK knockdown led to enrichment of G2/M phase cells, inactivation of DNA repair signaling mediated by heterodimerization of Ku80 and Ku70, and sensitization of EC cells to cisplatin treatment. IK/Ku80 mutations were accompanied by higher mutation rates and associated with significantly better overall survival. Inactivating mutations of IK gene and loss of IK protein expression were associated with weakened Ku80/Ku70-mediated DNA repair, increased mutation burden, and better response to chemotherapy in patients with EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13102487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160817PMC
May 2021

The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension.

Respir Res 2021 May 4;22(1):134. Epub 2021 May 4.

Department of Pathophysiology, School of Basic Medicine, Fourth Military Medical University, 169 Changle Western Street, Xi'an, Shaanxi, 710032, People's Republic of China.

Background: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.

Methods: In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (HO), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.

Results: Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (HO) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.

Conclusion: The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine HO into the pulmonary vascular microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01708-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094493PMC
May 2021

Harmine alleviates atherogenesis by inhibiting disturbed flow-mediated endothelial activation via protein tyrosine phosphatase PTPN14 and YAP.

Br J Pharmacol 2021 04 15;178(7):1524-1540. Epub 2021 Feb 15.

Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.

Background And Purpose: Disturbed flow induces endothelial dysfunction and contributes to uneven distribution of atherosclerotic plaque. Emerging evidence suggests that harmine, a natural constituent of extracts of Peganum harmala, has potent beneficial activities. Here, we investigated if harmine has an atheroprotective role under disturbed flow and the underlying mechanism.

Experimental Approach: Mice of ApoE , LDLR , and endothelial cell (EC)-specific overexpression of yes-associated protein (YAP) in ApoE background were fed with a Western diet and given harmine for 4 weeks. Atherosclerotic lesion size, cellular composition, and expression of inflammatory genes in the aortic roots were assessed. HUVECs were treated with oscillatory shear stress (OSS) and harmine and also used for proteomic analysis.

Key Results: Harmine retarded atherogenesis in both ApoE and LDLR mice by inhibiting the endothelial inflammatory response. Mechanistically, harmine blocked OSS-induced YAP nuclear translocation and EC activation by reducing phosphorylation of YAP at Y357. Overexpression of endothelial YAP blunted the beneficial effects of harmine in mice. Proteomic study revealed that protein tyrosine phosphatase non-receptor type 14 (PTPN14) could bind to YAP. Moreover, harmine increased PTPN14 expression by stabilizing its protein level and inhibiting its degradation in proteasomes. PTPN14 knockdown blocked the effects of harmine on YAP and EC activation. Finally, overexpression of PTPN14 mimicked the effects of harmine and ameliorated atherosclerosis, and knockdown of PTPN14 blunted the atheroprotective effects of harmine and accelerated atherosclerosis, in a partial ligation mouse model.

Conclusion And Implications: Harmine alleviated OSS-induced EC activation via a PTPN14/YAP pathway and had a potent atheroprotective role.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.15378DOI Listing
April 2021

Experimental Study of the Formation Rate and Distribution of Methane Hydrate in Layered Sand.

ACS Omega 2020 Nov 15;5(46):29882-29888. Epub 2020 Nov 15.

State Key Laboratory of Frozen Soil Engineering, Northwest Institute of Eco-Environment and Resources, CAS, Lanzhou 730000, China.

The geological structure and gas hydrate occurrence are stratification-dependent in the vertical direction. It is necessary to explore the formation processes and distribution characteristics of methane hydrate in layered porous media. The sand sample consists of two equal parts in a testing cylinder. The upper part is 0.5-1 mm sand in particle diameter, and the lower parts are 0.075∼0.5, 0.5∼1, and 1∼2 mm. The experimental results show that the formation rate of methane hydrate gradually decreases as the reaction goes on, and it is higher in layered sand than in nonlayered sand in the beginning. With the increase of the sand size in the lower part, saturation of methane hydrate gradually decreases in the upper part and increases in the lower part. In the layered sand, saturation of methane hydrate is higher in the sand layer whose particle size is bigger. The abovementioned results can be used to predict the favorable area where methane hydrate may appear in different stratigraphic structures in nature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.0c03984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689887PMC
November 2020

Decreased infiltration of CD4 Th1 cells indicates a good response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis.

Pathol Res Pract 2021 Jan 16;217:153291. Epub 2020 Nov 16.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Background: Primary biliary cholangitis (PBC) is characterized by nonsuppurative destructive cholangitis and is thought to be an autoimmune disorder. Currently, ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to nearly one-third of patients do not achieve a complete response to this treatment. Adaptive immune cells, including T cells and B cells, have been found in the portal tracts and the bile duct epithelium and play a role in the pathogenesis of PBC, but the importance of these cells for evaluating the therapeutic response to UDCA in PBC has not yet been studied.

Methods: In this study, we collected liver puncture biopsy specimens from 34 matched patients with PBC before and after UDCA treatment and investigated the relationship between the infiltration of adaptive immune cells and the treatment response to UDCA. The extent of immune cell infiltration was determined by immunohistochemical analysis. Responses were defined based on Paris-I criteria.

Results: After 1 year of treatment, 25/34 patients responded to UDCA treatment according to Paris-I criteria (responders), and 9/34 patients were nonresponders. Immunohistochemical analysis showed that UDCA responders exhibited significantly less CD4 T cell infiltration after UDCA treatment than before (50.4 ± 7.5/HPF vs 30.0 ± 7.9/HPF, P = 0.002). In contrast, UDCA nonresponders exhibited significantly more CD4 T cell infiltration after UDCA treatment than before (32.2 ± 8.0/HPF vs 75.0 ± 13.9/HPF, P = 0.045). Moreover, patients who exhibited a reduction in CD4 T cell infiltration after UDCA treatment had a higher response rate than those that exhibited an increase in CD4 T cell infiltration (85.7 % vs 53.8 %, P = 0.041). However, CD3 T cell, CD8 T cell, and CD20 B cell infiltration was not significantly different before and after treatment in either UDCA responders or nonresponders. Furthermore, we found that the number of infiltrating T-bet Th1 cells was much lower after UDCA treatment than before in responders (10.5 ± 5.7/HPF vs. 5.16 ± 4.0/HPF, P = 0.0214) but much higher in nonresponders after treatment than before (1.89±1.2/HPF vs. 12.3±5.4/HPF, P = 0.043). However, there was no difference in the extent of GATA3 Th2 or FOXP3 Treg infiltration before and after treatment in either UDCA responders or nonresponders.

Conclusion: Collectively, our results suggest that a decrease in the number of liver-infiltrating CD4 Th1 cells is associated with a good response of PBC patients to UDCA treatment. Immunohistochemical analysis of CD4 and T-bet in PBC liver specimens may be a potential approach for evaluating the therapeutic response to UDCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.153291DOI Listing
January 2021

The oncogenic role of SOX8 in endometrial carcinoma.

Cancer Biol Ther 2020 12 16;21(12):1136-1144. Epub 2020 Nov 16.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital , Tianjin, China.

Endometrial carcinoma (EC) remains one of the most prevalent forms of cancer to impact the female reproductive system, yet the mechanisms governing its development and progression are incompletely understood. We, therefore, sought to assess the relevance of SOX8 to EC progression and patient prognosis. Array comparative genomic hybridization (aCGH) was performed using samples from 50 patients with EC. Samples were separated based upon whether patients were positive for lymph node metastasis (LN+ and LN-, respectively). Based on our initial results, the SOX8 gene was selected for further analysis. Immunohistochemical staining of 630 endometrial tissue samples was conducted to understand how SOX8 expression relates to specific EC clinicopathological characteristics. In addition, we explored the impact of SOX8 expression on the growth, invasion, and migration of EC cells through knockdown and overexpression experiments. In our initial aCGH analysis, SOX family proteins and the Wnt and Notch signaling pathways were significantly associated with EC LN metastasis. SOX8 expression was markedly increased in EC tumor samples relative to normal endometrial tissue (= .003), and higher SOX8 expression was linked to a high tumor histological grade (= .032), LN metastasis (= .027), and shorter patient overall survival (= .031). When SOX8 was knocked down, this further impaired the proliferative, invasive, and migratory activity of EC cells, whereas overexpressing this gene had the opposite effect. SOX8 may function in an oncogenic manner to drive EC development and progression, and higher SOX8 expression is associated with a poor EC patient prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15384047.2020.1840318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722791PMC
December 2020

The clinicopathological and molecular features of sinusoidal large B-cell lymphoma.

Mod Pathol 2021 05 24;34(5):922-933. Epub 2020 Sep 24.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue. All tumors contained large pleomorphic lymphoid cells and one or more prominent nucleoli, with abundant amphophilic cytoplasms; 15/17 cases showed anaplastic morphologic features. The patient age ranged from 43 to 80 years (median 57 years), and 7 males and 10 females were included. Eleven of 15 (73.3%) patients had Ann Arbor stage III or IV disease, and 10/15 (66.6%) patients had an International Prognostic Index (IPI) score ≥3. Immunophenotypically, 16/17 (94.1%) cases displayed a nongerminal center B-cell (non-GCB) immunophenotype. Furthermore, 16/17 (94.1%) cases were positive for CD30, and p53 was expressed in 10/16 (62.5%) cases. In total, 12/14 (85.7%) cases expressed BCL2 and MYC simultaneously (double expression), and 11/14 (78.6%) cases showed PD-L1 positivity (6/11 had a PD-L1 tumor proportion score ≥50%). Cytogenetically, concurrent MYC and BCL2 and/or BCL6 abnormalities (break-apart or extra copy) were detected in 10/15 cases, and 7/13 (53.8%) cases harbored a PD-L1/L2 amplification. TP53 mutation was found in 7/13 (53.8%) cases by Sanger sequencing. Whole-exome and large-panel sequencing results revealed high mutation frequencies of TP53 (4/7), MYD88 (3/7), KMT2D (3/7), CREBBP (3/7), and PIM1 (3/7). Among the 13 patients with SLBCL treated with aggressive chemotherapy regimens, the median overall survival (OS) was 18 months, and the 2-year OS rate was 34.6%. The OS of patients with SLBCL was markedly worse than that of 35 control group patients with common diffuse large B-cell lymphoma (DLBCL) without sinusoidal features (P < 0.001). SLBCL may represent a specific type of DLBCL that has characteristic pathologic features. The cancer is aggressive in most clinical cases, and outcomes are poor. SLBCL and anaplastic DLBCL (A-DLBCL) have many overlapping clinicopathological and molecular features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-00685-7DOI Listing
May 2021

High serum Androgen and Insulin concentrations increase the tendency of Endometrial Carcinoma.

J Cancer 2020 25;11(19):5656-5664. Epub 2020 Jul 25.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.

The objective of the study was to evaluate the important role played by androgen and insulin in the development of endometrial carcinoma (EC), and their combined effect on EC risk. We enrolled 510 type I EC patients and 510 age-, time-, and nationality-matched subjects into this study. Metabolic and hormonal parameters of enrolled subjects were examined. Univariate and multivariate logistic regression analyses for EC and control subjects were performed. Type I EC risk was evaluated with respect to testosterone, androstenedione, and insulin levels based on odds ratios (ORs) using stratified data. EC risk was positively associated with C-peptide, estrone, androgen (including testosterone and androstenedione) and insulin levels, BMI, WHR, family history of cancer, nulliparity, irregular menstruation, diabetes, and hypertension. In multivariate logistic regression models, high C-peptide and testosterone levels, diabetes, and hypertension were independent risk factors after adjustment for BMI, WHR, family history of cancer, high serum insulin, and estrone levels. Increased serum total testosterone and insulin levels were positively correlated with EC risk in total, premenopausal, and postmenopausal women. Androstenedione was correlated with EC in total and postmenopausal, but not in premenopausal subjects. Compared with higher testosterone and insulin, odds ratios (ORs) for higher testosterone with lower insulin and lower testosterone with higher insulin were decreased in total, premenopausal, and postmenopausal women. Similarly, compared to both higher FAI and insulin, ORs for higher FAI with lower insulin and lower FAI with higher insulin were decreased in all three groups. Coordinately, ORs for higher androstenedione with lower insulin and lower androstenedione with higher insulin were decreased in total and postmenopausal, but not premenopausal subjects. These findings suggested that androgen and insulin were risk factors of type I EC, and relatively high levels of both testosterone and insulin synergistically affected EC risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.46391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477453PMC
July 2020

p63 expression is associated with high histological grade, aberrant p53 expression and TP53 mutation in HER2-positive breast carcinoma.

J Clin Pathol 2020 Sep 1. Epub 2020 Sep 1.

Department of Pathology, The Basic Medicine Science and the First Affiliated Hospital of the Air Force Military Medical University, Xi'an, China.

Aim: p63, a member of the p53 family, is a myoepithelial cell marker usually expressed in metaplastic breast carcinoma and its expression suggests a myoepithelial phenotype. However, its expression and association with clinicopathological features of human epidermal growth factor receptor 2 (HER 2)-positive breast carcinoma is poorly investigated.

Materials And Methods: Sixty-seven patients with oestrogen receptor-negative and progesterone receptor-negative, HER2-positive breast carcinoma who received anti-HER2-based neoadjuvant±adjuvant therapy was retrospectively analysed.

Results: Twenty cases were p63-positive and 47 cases were p63-negative. The clinicopathological features and tumour responses after neoadjuvant therapy and outcomes were analysed. Among HER2-positive tumours, expression of p63 was significantly associated with younger age (42.5 vs 55.9; p=0.010). Expression of p63 was also significantly associated with histological grade 3 (11/20 (55%) vs 11/47 (23.4%); p=0.012) and negatively associated with grade 2 (9/20 (45%) vs 36/47 (76.6%); p=0.012). Intriguingly, p63-positive breast carcinomas showed significant aberrant p53 expression by immunohistochemistry (16/18 (88.9%) vs 29/47 (61.7%); p=0.03) and of mutation by Sanger sequencing (15/16 (93.8%) vs 12/22 (54.5%); p=0.009). No significant difference in tumour response after anti-HER2 neoadjuvant therapy nor in survival were found between p63-positive and p63-negative breast carcinomas.

Conclusion: Expression of p63 in HER2-positive breast carcinoma is significantly associated with younger age, poor differentiation, high histological grade and aberrant expression of p53 and of mutation. HER2-positive breast carcinoma with a myoepithelial immunophenotype shows distinctive clinicopathological features representing a distinct subtype of HER2-positive breast carcinoma. Further, these findings suggest an interaction between p63 and mutant p53 in the tumorigenesis of HER2-positive breast carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2020-206643DOI Listing
September 2020

Cross‑validation of genes potentially associated with neoadjuvant chemotherapy and platinum‑based chemoresistance in epithelial ovarian carcinoma.

Oncol Rep 2020 Sep 2;44(3):909-926. Epub 2020 Jul 2.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian carcinomas have the poorest prognosis and the highest mortality among gynecological malignancies. Neoadjuvant chemotherapy (NACT) is considered as a novel therapeutic strategy and an alternative treatment for advanced epithelial ovarian cancer (AEOC). The aim of the present study was to identify the core genes related to platinum‑based NACT resistance in AEOC and to allow screening at the molecular level for the most appropriate ovarian cancer patients for NACT. We obtained three drug‑resistant microarrays GSE114206, GSE41499 and GSE33482 from the Gene Expression Omnibus (GEO) database as well as a microarray representing NACT, GSE109934. Bioinformatics analysis revealed the nature of the four potential candidate genes for using in functional enrichment analyses and interaction network construction. The potential associations and possible genetic alterations among the DEGs were summarized using the STRING database in Cytoscape and the cBioPortal visualization tool, respectively. A total of 63 genes were identified as DEGs from GSE109934 representing NACT. From the drug‑resistant GSE114206 and GSE41499 datasets, 106 DEGs containing 36 upregulated genes and 70 downregulated genes were selected, and from the drug‑resistant GSE114206 and GSE33482 datasets, 406 DEGs with 157 upregulated genes and 249 downregulated genes were selected. The 36 upregulated DEGs and the 70 downregulated genes were notably abundant in the different categories. In KEGG pathway analysis, the 157 upregulated genes and the 249 downregulated genes were concentrated in distinctive signaling pathways. Four potential genes associated with NACT and platinum‑based chemoresistance were screened, including nuclear factor of activated T‑cells, cytoplasmic 1 (NAFTc1), Kruppel‑like factor 4 (KLF4), nuclear receptor subfamily 4 group A member 3 (NR4A3) and hepatocyte growth factor (HGF). Our study showed that the mRNA expression levels of NAFTc1, NR4A3 and HGF were increased in drug‑resistant OC cell lines (all P<0.01), whereas the mRNA expression levels of KLF4 were notably lower in the SKOV3‑CDDP and HeyA8‑CDDP cell line (all P<0.01) but higher in the A2780‑CBP cell line. The NAFTc1, KLF4, NR4A3 and HGF genes may be potential therapeutic targets for NACT and platinum‑based chemoresistance factors as well as candidate biomarkers in AEOC. Determination of the expression levels of these four genes in tumor tissues before planning NACT treatment or initial surgery would be beneficial for AEOC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2020.7668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388274PMC
September 2020

Recommendations on management of gynecological malignancies during the COVID-19 pandemic: perspectives from Chinese gynecological oncologists.

J Gynecol Oncol 2020 07 27;31(4):e68. Epub 2020 May 27.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 has rapidly spread globally. Cancer patients are at a higher risk of being infected with the coronavirus and are more likely to develop severe complications, as compared to the general population. The increasing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Concerted efforts should be put into managing gynecological malignancies in an orderly manner by strictly implementing the measures that are specifically developed for controlling the spread of COVID-19. We have drafted based on our experience on controlling COVID-19 pandemic in China. We recommend that patients with gynecological malignancies should be managed in hierarchical and individualized manners in combination with local conditions related to COVID-19. Medical care decision should be balanced between controlling COVID-19 pandemic spread and timely diagnosis and treatment for gynecologic oncology patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2020.31.e68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286750PMC
July 2020

MAP7 interacts with RC3H1 and cooperatively regulate cell-cycle progression of cervical cancer cells via activating the NF-κB signaling.

Biochem Biophys Res Commun 2020 06 25;527(1):56-63. Epub 2020 Apr 25.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, 300052, China. Electronic address:

Ensconsin is encoded by the MAP7 gene and belongs to the microtubule-associated proteins. This study aimed to explore its functional roles and partners in cell-cycle progression in cervical cancer. Data from the Cancer Genome Atlas-Cervical & Endocervical Cancer (TCGA-CESC) and the Genotype-Tissue Expression project were used for bioinformatic analysis. SiHa cells were used for in-vitro and in-vivo analysis. Co-immunoprecipitation (Co-IP) assay was conducted to explore the proteins interacted with MAP7. Results showed that MAP7 mRNA expression might serve as an independent biomarker of shorter survival. MAP7 overexpression elevated cyclin D1/cyclin B1 expression, facilitated cell-cycle progression and promoted SiHa cell growth in a xenograft tumor model. Co-IP experiments confirmed a novel interaction between MAP7 and RC3H1. Knockdown of either RC3H1 or MAP7 significantly attenuated cyclin D1/cyclin B1 upregulation, and cell-cycle progression induced by the other partner. MAP7 overexpression led to increased expression of P-IKK (Ser176/177) and P-p65 (Ser536). RC3H1 inhibition abrogated MAP7 induced upregulation of P-IKK and P-p65. Data in TCGA-CESC showed that MAP7 expression was positively correlated with its copy number segments, but was negatively correlated with the methylation level of three CpG sites within the gene locus. Demethylation treatment by 5-Aza-dC elevated both MAP7 mRNA and protein expression in a dose-dependent manner. In conclusion, this study revealed a novel interaction between MAP7 and RC3H1 in cervical cancer cells, which cooperatively enhanced cyclin D1/cyclin B1 expression and facilitated cell-cycle progression. These effects were at least partly mediated by activated canonical IKK/NF-kB signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2020.04.008DOI Listing
June 2020

miR‑508‑3p suppresses the development of ovarian carcinoma by targeting CCNA2 and MMP7.

Int J Oncol 2020 07 27;57(1):264-276. Epub 2020 Apr 27.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Ovarian cancer is the most lethal gynecological tumor, and the 5‑year survival rate is only ~40%. The poor survival rate is due to cancer diagnosis at an advanced stage, when the tumor has metastasized. A better understanding of the molecular pathogenesis of tumor growth and metastasis is needed to improve patient prognosis. MicroRNAs (miRs) regulate carcinogenesis and development of cancers. However, the role of miR‑508‑3p in ovarian cancer remains largely unknown. Thus, the present study aimed to investigate the possible functions of miR‑508‑3p in the modulation of development of ovarian cancer. The results of the present study demonstrated that miR‑508‑3p mimics inhibited ovarian cancer cell proliferation, migration and invasion. Reporter gene assay results demonstrated that miR‑508‑3p suppressed cancer cell proliferation by directly targeting the 3'‑untranslated region (UTR) of cyclin A2 (CCNA2) and suppressed migration and invasion by directly targeting the 3'‑UTR of matrix metalloproteinase 7 (MMP7). In addition, high CCNA2 and MMP7 expression levels were associated with low miR‑508‑3p expression in ovarian cancer tissues. Furthermore, miR‑508‑3p and CCNA2 were independent predictors for overall survival in patients with ovarian cancer. To the best of our knowledge, this is the first study to demonstrated that miR‑508‑3p suppressed ovarian cancer development by directly targeting CCNA2 and MMP7. The results of this study suggested the potential value of miR‑508‑3p and CCNA2 as prognostic indicators and therapeutics for ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2020.5055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252466PMC
July 2020

The Proportion and Prognostic Significance of T-Regulatory Cells in Patients with Gynecological Cancers: A Systematic Review and Meta-Analysis.

J Cancer 2020 5;11(11):3340-3348. Epub 2020 Mar 5.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, 154 Anshan Road, He Ping District, Tianjin 300052, China.

: Multiple reports have described the proportion of T-regulatory cells (Tregs) in peripheral blood (PB) and tissues in patients with gynecological cancers (GCs) with controversial results. Thus, the aim of this study was to investigate the proportion of Tregs and its prognostic survival role in GCs patients. : We performed a comprehensive search from database inception for all studies presenting changes of Tregs in GCs patients versus controls to evaluate the pooled standardized mean differences (SMD) with 95% confidence intervals (95% CI). And hazard ratios (HRs) with 95% CI were recorded if available to determine the prognostic significance of Tregs. : Totally, 22 studies were included. Compared with controls, GCs patients had a higher proportion of Tregs in PB (SMD = 2.32, 95% CI = 1.47 to 3.17, = 0.000) as well as in tissues (SMD = 3.47, 95% CI = 0.77 to 6.18, = 0.012). Furthermore, more significant elevated frequency of Tregs was observed in GCs patients with advanced stage than those in the early stage in both PB and tissues. However, no association was found between Tregs and survival of GCs patients with an HR of 1.34 (95% CI = 0.96 to 1.88, = 0.09). : Compared to controls, proportion of Tregs in PB and tissues was both higher among GCs patients, and it can be considered as a clinical biomarker for screening and prediction of clinical characteristics of GCs patients. But larger researches with rigorous design should be carried to explore the deep mechanisms of Tregs in GCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.42472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097934PMC
March 2020

Wild-Type IDH1 and Mutant IDH1 Opposingly Regulate Podoplanin Expression in Glioma.

Transl Oncol 2020 Apr 21;13(4):100758. Epub 2020 Mar 21.

State Key Laboratory of Cancer Biology and Department of Pathology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China, 710032; Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China, 710032. Electronic address:

Isocitrate dehydrogenase (IDH) mutations occur frequently in lower-grade gliomas, which result in genome-wide epigenetic alterations. The wild-type IDH1 is reported to participate in lipid biosynthesis and amino acid metabolism, but its role in tumorigenesis is still unclear. In this study, the expressions of IDH1 and podoplanin (Pdpn) were determined in IDH-mutated and IDH-wild-type gliomas, and their relationships in glioma were further analyzed. In addition, the regulation of wild-type IDH1 and mutant IDH1 on Pdpn expression was investigated by luciferase assays and promoter methylation analysis. Our study showed that Pdpn was almost undetectable in IDH-mutated glioma but strongly expressed in higher-grade IDH-wild-type glioma. Pdpn overexpression promoted the migration of glioma cells but had little effect on cell growth. Moreover, Pdpn expression was positively correlated with the increased wild-type IDH1 levels in IDH-wild-type glioma. Consistently, the wild-type IDH1 greatly promoted the transcription and expression of Pdpn, but the mutant IDH1 and D-2-hydroxyglutarate significantly suppressed Pdpn expression in glioma cells. Besides, our results revealed that the methylation of CpG islands in the Pdpn promoter was opposingly regulated by wild-type and mutant IDH1 in glioma. Collectively, our results indicated that wild-type and mutant IDH1 opposingly controlled the Pdpn expression in glioma by regulating its promoter methylation, which provides a basis for understanding the relationship between wild-type and mutant IDH1 in epigenetic regulation and tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2020.100758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097522PMC
April 2020

Vaginal bacterial profiles of aerobic vaginitis: a case-control study.

Diagn Microbiol Infect Dis 2020 Apr 7;96(4):114981. Epub 2020 Jan 7.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

Purpose: Aerobic vaginitis (AV) has drawn increasing attention because of its threat to women's reproductive health and pregnancy. However, little is known about the overall structure of vaginal bacterial communities in women with AV.

Methods: The diversity of vaginal microbiota was evaluated by amplicon sequencing targeting the 16S rRNA V4 region. Routine laboratory tests, including cultivation, were used.

Results: Firmicutes (mainly Lactobacillus crispatus and L. iners) were dominant in healthy women (n = 160), while Actinobacteria and Bacteroidetes were strongly associated with AV (n = 80). The onset of AV was marked by a striking decline in L. crispatus and an increase in multiple aerobes, including Streptococcus agalactiae, S. anginosus, etc. The overall drug resistance level of gram-positive bacteria against erythromycin and clindamycin was high, and the overall drug resistance level of gram-negative bacteria against ampicillin was high.

Conclusions: Multiple aerobes and facultative anaerobes were involved in vaginal dysbiosis, which was associated with decreasing L. crispatus levels. Probiotics containing L. crispatus may be potential supplementary agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diagmicrobio.2019.114981DOI Listing
April 2020

Genome-wide analysis of alternative splicing differences between oocyte and zygote†.

Biol Reprod 2020 04;102(5):999-1010

Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, People's Republic of China.

Alternative splicing (AS) of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, significantly expanding the information content and regulatory possibilities of higher eukaryotic genomes. During mammalian development, AS drives certain decisive changes in different physiological processes. As development progresses, the maternal-to-zygotic transition (MZT) will trigger two processes: elimination of a subset of maternal mRNA and transcription of the zygote genome begins. Recent high-throughput technological advancements have facilitated genome-wide AS, whereas its analysis in mouse oocyte transition to the zygote stage has not been reported. We present a high-resolution global analysis of AS transitions and discovered extensive AS transitions between mouse oocyte and zygote. The difference of AS patterns was further confirmed using reverse transcription-polymerase chain reaction analysis. Many genes with specific AS events in mouse oocytes are differentially expressed between oocyte and zygote, but only a few genes with specific AS events in zygote are differentially expressed between oocyte and zygote. We provide a landscape of AS events in mouse oocyte and zygote. Our results advance the understanding of AS transitions during mouse fertilization and its potential functions for MZT and further development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biolre/ioaa004DOI Listing
April 2020

Incarceration of the gravid uterus: a case report and literature review.

BMC Pregnancy Childbirth 2019 Nov 8;19(1):408. Epub 2019 Nov 8.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, People's Republic of China, 300052.

Background: Incarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient.

Case Presentation: A 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy.

Conclusions: Uterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-019-2549-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839127PMC
November 2019

Syncytiotrophoblast-Derived Extracellular Vesicles in Pathophysiology of Preeclampsia.

Front Physiol 2019 1;10:1236. Epub 2019 Oct 1.

Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin, China.

Preeclampsia is a common obstetric complication associated with pregnancy and it endangers lives of the mother and the infant. The histopathological changes associated with preeclampsia include systemic endothelial dysfunction, persistent inflammatory state, and coagulation and fibrinolysis dysregulations. Preeclampsia is considered to be caused by the systemic vasoconstriction of small arteries and disruption of the endothelial integrity, resulting in hypertension, proteinuria, and multiple organ dysfunction. However, mediators that trigger or propagate the pathology of preeclampsia remain poorly defined. Syncytiotrophoblast-derived extracellular vesicles (SDEVs) are increasingly recognized as a key mediator for the development of preeclampsia, but the underlying mechanisms through which these SDEVs are released and induce systemic responses are not fully understood. This review focuses on multiple roles of SDEVs in the pathogenesis of preeclampsia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2019.01236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779799PMC
October 2019

Small-cell carcinoma-associated ovarian mucinous carcinoma: A case report and literature review.

Pathol Res Pract 2019 Nov 27;215(11):152619. Epub 2019 Aug 27.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, the Air Force Military Medical University. No.169 Changlexi Road, Xincheng District, Xi'an 710032, PR China. Electronic address:

Neuroendocrine neoplasm-associated ovarian mucinous carcinoma occurs extremely rarely. Here, we report an ovarian composite tumor consisting of small-cell carcinoma and mucinous carcinoma in a 51-year-old woman presented with abdominal distention. Ultrasonography revealed the presence of a complex irregular cystic solid mass. Microscopic findings showed pulmonary-type small-cell carcinoma-associated, intestinal-type ovarian mucinous carcinoma-with positive results for several neuroendocrine markers (chromogranin, CD56) and the thyroid transcription factor-1. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and six cycles of adjuvant chemotherapy but died eight months after the surgery due to disease progression. Few reports are available in China on this clinicopathological feature in this composite tumor type. The timely identification of ovarian small-cell carcinoma among other ovarian tumors is critically important to the accurate and prompt determination of the therapy due to its high invasiveness and metastatic potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2019.152619DOI Listing
November 2019

Genetic alterations in cell cycle regulation-associated genes may promote primary progression of gastrointestinal stromal tumors.

Lab Invest 2020 03 30;100(3):426-437. Epub 2019 Sep 30.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaan Xi, China.

Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumor types and usually contain KIT or PDGFRA mutations. GISTs with concomitant low- and high-grade components are seen in clinical practice. Herein, we retrospectively analyzed the histological characteristics and immunohistochemical results of 22 GIST cases with concomitant low- and high-grade tumors. Whole-exome sequencing (WES) was performed on ten pairs of high-grade GIST specimens and matched low-grade samples. Differential oncogenes mutated only in high-grade GISTs were identified, which were confirmed by Sanger sequencing. Fluorescence in situ hybridization was employed to detect MYC copy number variation. High-grade GISTs were more likely to have lower CD34 expression and a higher Ki-67 proliferation index compared to the matched low-grade tumors. WES identified 30 differential cancer-associated genes mutated only in high-grade GISTs; Sanger sequencing confirmed ten relevant differential oncogenic mutations in nine genes (MGA, ARID1A, LATS2, MAX, PIK3CA, RB1, RPS6KB2, SDHA, and SETD2). Two patients had MGA mutations, whereas other gene mutations occurred in only one patient. Most of the differential cancer-associated genes are mainly involved in cell cycle control. MYC copy number gain was a common genetic variation. High-grade GISTs revealed more MYC copy number gains than matched low-grade tumors, and low-grade GISTs with coexisting high-grade components showed more MYC copy number gains than pure low-grade GISTs. Moreover, MYC copy number gain was positively correlated with the mitotic index and Ki-67 proliferation index. Alterations in cell cycle regulation-associated genes, such as genetic mutations and MYC copy number gain, may promote primary progression from low-grade GISTs to high-grade tumors by regulating tumor cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41374-019-0322-xDOI Listing
March 2020

genes: regulators and biomarkers in gynecological cancers.

Cancer Biol Med 2019 Aug;16(3):462-474

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, China.

genes are transcription factors with roles in multiple biological processes, including cell differentiation, proliferation, and apoptosis. genes have also been shown to act as regulators and biomarkers in the progression of many different cancers, including gynecological cancers such as ovarian, cervical, and endometrial cancer. In this review, we summarize the contrasting regulatory roles of genes in different gynecological cancers, as promotors with high expression levels or as suppressors with low expression levels. Expression levels of genes were also identified as biomarkers of clinical features, including International Federation of Gynecology and Obstetrics stage, histopathologic grade together with disease-free survival, and treatment efficacy in patients with gynecological cancers. An understanding of the mechanisms whereby genes regulate the progression of gynecological cancers will aid in the development of novel diagnostic and therapeutic strategies, while analysis of expression levels will help to predict the prognosis of patients with gynecological cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2019.0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743626PMC
August 2019

Lineage-negative lymphoma with a helper innate lymphoid cell phenotype.

Virchows Arch 2020 Feb 14;476(2):285-293. Epub 2019 Sep 14.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.

Helper innate lymphoid cells (ILCs) were recently recognized as lineage-negative lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity. However, to our knowledge, no cases of hematological malignancies arising from helper ILCs have ever been reported in the literature. Here, we report a case of a 17-year-old man with multiple lymphadenopathy who was diagnosed with lineage-negative lymphoma that displayed a helper ILC phenotype. Histological examination showed large monomorphic atypical lymphoid cells with prominent nucleoli and abundant eosinophilic cytoplasms with scattered and patchy distributions. Large amounts of histiocytes and infiltrating lymphocytes were observed in the background. Immunostaining revealed positive LCA and CD79a expression but negative expression of all lineage markers. IG and TCR rearrangement analysis showed no clonal rearrangements. Tumor cells strongly expressed helper ILC phenotypic markers, such as CD127, IL-1R, GATA3, ST2, IL-17Rβ, and RANKL, and helper ILC-produced cytokines, such as IL-4 and GM-CSF. PD-L1/PD-L2-positive histiocytes and FOXP3-positive Tregs were observed in the tumor microenvironment. Flow cytometry of bone marrow at recurrence was positive for IL-1R and negative for T, B, NK, and myelogenous lineage markers. TP53 sequencing showed that exon 5 was replaced with an intergenic sequence of chromosome 21. Next-generation sequencing demonstrated a novel IGLV2-14/IGLL5 fusion and mutations or deletions of tumor suppressor genes, such as PTPRB, PPP2CB, and UPK1A. This tumor was very aggressive, resistant to chemotherapy, recurred with bone marrow involvement, and caused the death of the patient within 6 months. To our knowledge, this is the first report of a hematological malignancy potentially arising from helper ILCs. We propose negativity for lineage markers and positivity for CD127/IL-1R in combination with specific transcription factor expression as markers of this tumor. This finding represents a novel addition to the growing spectrum of hematological malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-019-02658-xDOI Listing
February 2020

Identification of key genes and pathways between type I and type II endometrial cancer using bioinformatics analysis.

Oncol Lett 2019 Sep 28;18(3):2464-2476. Epub 2019 Jun 28.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.

Endometrial carcinoma (EC) is a common malignant neoplasm of the female reproductive tract. The malignant degree of type II EC is much greater than that of type I EC, usually presenting with a high recurrence rate and a poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in type I and type II EC and reveal their potential mechanisms. Differentially expressed genes (DEGs) were selected from the gene expression profiles derived from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. In the present study, the KEGG pathway enrichment analysis revealed that 5,962 upregulated DEGs were significantly enriched in the 'p53 signaling pathway' and involved in 'lysine degradation'. In addition, 3,709 downregulated DEGs were enriched in 'pathways in cancer', as well as 'tight junction regulation', the 'cell cycle' and the 'Wnt signaling pathway'. The 13 top hub genes MAPK1, PHLPP1, ESR1, MDM2, CDKN2A, CDKN1A, AURKA, BCL2L1, POLQ, PIK3R3, RHOQ, EIF4E and LATS2 were identified via the protein-protein interaction network. Furthermore, the OncoPrint algorithm from cBioPortal declared that 25% of EC cases carried genetic alterations. The altered DEGs (MAPK1, MDM2, AURKA, EIF4E and LATS2) may be involved in tumor differentiation and may be valuable diagnostic biomarkers. In conclusion, a number of principal genes were identified in the present study that may be determinants of poorly differentiated type II EC carcinogenesis, which may contribute to future research into potential molecular mechanisms. In addition, these genes may help identify candidate biomarkers and novel therapeutic targets for type II EC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2019.10550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676660PMC
September 2019
-->