Publications by authors named "Masanobu Kitagawa"

115 Publications

Synovial sarcoma of the stomach: a case report and a systematic review of literature.

Clin J Gastroenterol 2021 Apr 12. Epub 2021 Apr 12.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Worldwide, 5-10% of soft tissue sarcoma cases in adults have been attributed to synovial sarcoma. It is often reported to occur near the joints of the arm, neck, and leg but rarely in the gastrointestinal tract. In this study, we report a case of synovial sarcoma arising in the stomach of a 59-year-old woman. Gastrointestinal endoscopy revealed an ulcerative and hemorrhagic tumor with marginal elevation in the fundus. Histological study showed that the tumor was composed of tightly packed spindle cells in bundles, and one of its component demonstrated significant mitotic activity (> 40/10 high-power fields) in several areas. The diagnosis was confirmed by the evidence of SS18 gene rearrangement, according to immunohistochemistry study, (including a novel SS18-SSX fusion-specific antibody), fluorescent in situ hybridization, and the identification of the SS18-SSX1 and SS18-SSX1/2/4 fusion transcripts using reverse-transcript polymerase chain reaction. No evidence of local recurrence or distant metastasis has been found in the more than 5 years since. Distinguishing synovial sarcoma in the digestive tract from other mesenchymal neoplasms, such as gastrointestinal stromal tumor, may be difficult, especially when spindle-shaped cell proliferation is predominant, as in our patient. Therefore, morphological, immunohistological, and molecular evaluations are important for a comprehensive diagnosis.
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http://dx.doi.org/10.1007/s12328-021-01408-4DOI Listing
April 2021

Nodular lymphocyte-predominant Hodgkin lymphoma involving the hard palate.

Pathol Int 2021 Mar 27;71(3):213-215. Epub 2021 Jan 27.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

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http://dx.doi.org/10.1111/pin.13061DOI Listing
March 2021

Combined Use of Immunoreactivities of RIG-I with Efp/TRIM25 for Predicting Prognosis of Patients With Estrogen Receptor-positive Breast Cancer.

Clin Breast Cancer 2020 Dec 9. Epub 2020 Dec 9.

Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. Electronic address:

Background: We previously identified estrogen-responsive finger protein (Efp) as an estrogen-induced gene, and showed that the positive immunoreactivity of Efp is a poor prognostic factor for patients with breast cancer. We also demonstrated that Efp has distinctive roles in innate immunity by activating pattern recognition receptor retinoic acid-inducible gene I (RIG-I). The clinical value of RIG-I protein expression in breast cancer had not been evaluated in relationship with patients' prognosis.

Patients And Methods: Tissue samples of estrogen receptor-positive invasive breast cancer were obtained from 145 female patients with breast cancer who underwent surgical treatment. Immunoreactivities of RIG-I and Efp were analyzed with the antibodies generated for the present study.

Results: Positive immunoreactivity of RIG-I was correlated with lower disease-free survival (P = .032) and was an independent poor prognostic factor (P = .043). RIG-I immunoreactivity was positively correlated with that of Efp (P = .0004). Patients with positive immunoreactivities of both RIG-I and Efp proteins were associated with a lower disease-free survival rate (P = .005).

Conclusions: Positive immunoreactivity of RIG-I has clinical significance as a poor prognostic factor in patients with estrogen receptor-positive breast cancer. A positive correlation of RIG-I and Efp immunoreactivities was observed, and the combination of their immunoreactivities can be used to predict patients' prognosis.
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http://dx.doi.org/10.1016/j.clbc.2020.12.001DOI Listing
December 2020

Adenocarcinoma arising in the multiple heterotopic submucosal glands of the intestine in a Satoyoshi syndrome patient: A case report.

Pathol Int 2021 Feb 17;71(2):147-154. Epub 2020 Dec 17.

Department of Comprehensive Pathology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.

Satoyoshi syndrome is a rare multisystemic disorder of unknown etiology characterized by progressive muscle spasms, alopecia and diarrhea. Multiple protruding lesions with cystic glands, namely gastroenterocolitis cystica polyposa, manifest in the gastrointestinal tract. Since the first report of these lesions in 1977, which was unique to Satoyoshi syndrome, few studies have focused on their role, and the associated clinicopathological features are not well understood. Here, we report a 64-year-old Japanese woman with Satoyoshi syndrome who presented with multiple polypoid lesions in the stomach, duodenum, jejunum, ileum and colon. Histologically, the polypoid lesions in the intestine comprised multiple heterotopic submucosal glands containing cystically dilated glands and smooth muscle fibers in the lamina propria mucosa and/or submucosa. Additionally, we observed stromal changes, such as fibrosis, discontinuous and thinning muscularis mucosae, and diffuse neural fiber proliferation in the entire intestinal tract. Furthermore, multiple foci of adenocarcinomas were identified within several heterotopic submucosal glands. We hypothesized that multiple heterotopic submucosal glands in the present case corresponded to previously reported gastroenterocolitis cystica polyposa, suggesting that these lesions are essential in the histopathology and are a unique manifestation of Satoyoshi syndrome.
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http://dx.doi.org/10.1111/pin.13053DOI Listing
February 2021

Intestinal phenotype is maintained by Atoh1 in the cancer region of intraductal papillary mucinous neoplasm.

Cancer Sci 2021 Feb 18;112(2):932-944. Epub 2020 Dec 18.

Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal-type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal-type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive-grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal-type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal-type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.
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http://dx.doi.org/10.1111/cas.14755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894004PMC
February 2021

Combined A20 and tripartite motif-containing 44 as poor prognostic factors for breast cancer patients of the Japanese population.

Pathol Int 2021 Jan 7;71(1):60-69. Epub 2020 Nov 7.

Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

We previously reported that a strong immunoreactivity of tripartite motif-containing 44 (TRIM44) predicts the poor prognosis of patients with invasive breast cancer, and proposed that TRIM44 activates nuclear factor-κB (NF-κB) signaling as a causative mechanism. In the present study, we examined the clinicopathological roles of A20, which is known to be an NF-κB responsive gene, with TRIM44, in an updated cohort. Tissue samples of invasive breast cancer were obtained from 140 Japanese female breast cancer patients who underwent surgical treatment. Immunoreactivities of A20 and TRIM44 were analyzed using specific antibodies for each protein. A positive A20 immunoreactivity was significantly associated with a shorter disease-free survival (P = 0.043) and was positively correlated with TRIM44 immunoreactivity (P = 0.039). Combined use of the immunoreactivities for two proteins revealed that double-positive status for both A20 and TRIM44 immunoreactivities was associated with a shorter disease-free survival (P = 0.012) and was an independent factor for poor prognosis. These results indicate that a combined A20 and TRIM44 immunoreactivity predicted the prognosis of patients with invasive breast cancer. Moreover, the positive correlation between A20 and TRIM44 immunoreactivities suggested that the activation of NF-κB signaling by TRIM44 could occur in clinical breast cancer tissues.
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http://dx.doi.org/10.1111/pin.13047DOI Listing
January 2021

SECISBP2 is a novel prognostic predictor that regulates selenoproteins in diffuse large B-cell lymphoma.

Lab Invest 2021 02 19;101(2):218-227. Epub 2020 Oct 19.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

The overexpression of glutathione peroxidase 4 (GPX4; an enzyme that suppresses peroxidation of membrane phospholipids) is considered a poor prognostic predictor of diffuse large B-cell lymphoma (DLBCL). However, the mechanisms employed in GPX4 overexpression remain unknown. GPX4 is translated as a complete protein upon the binding of SECISBP2 to the selenocysteine insertion sequence (SECIS) on the 3'UTR of GPX4 mRNA. In this study, we investigated the expression of SECISBP2 and its subsequent regulation of GPX4 and TXNRD1 in DLBCL patients. Moreover, we determined the significance of the expression of these selenoproteins in vitro using MD901 and Raji cells. SECISBP2 was positive in 45.5% (75/165 cases) of DLBCL samples. The SECISBP2-positive group was associated with low overall survival (OS) as compared to the SECISBP2-negative group (P = 0.006). Similarly, the SECISBP2 and GPX4 or TXNRD1 double-positive groups (P < 0.001), as well as the SECISBP2, GPX4, and TXNRD1 triple-positive group correlated with poor OS (P = 0.001), suggesting that SECISBP2 may serve as an independent prognostic predictor for DLBCL (hazard ratio (HR): 2.693, P = 0.008). In addition, western blotting showed a decrease in GPX4 and TXNRD1 levels in SECISBP2-knockout (KO) MD901 and Raji cells. Oxidative stress increased the accumulation of reactive oxygen species in SECISBP2-KO cells (MD901; P < 0.001, Raji; P = 0.020), and reduced cell proliferation (MD901; P = 0.001, Raji; P = 0.030), suggesting that SECISBP2-KO suppressed resistance to oxidative stress. Doxorubicin treatment increased the rate of cell death in SECISBP2-KO cells (MD901; P < 0.001, Raji; P = 0.048). Removal of oxidative stress inhibited the altered cell death rate. Taken together, our results suggest that SECISBP2 may be a novel therapeutic target in DLBCL.
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http://dx.doi.org/10.1038/s41374-020-00495-0DOI Listing
February 2021

Acute Spinal Cord Infarction with Preferential Involvement of Ventral Gray Matter: An Autopsy Report.

J Stroke Cerebrovasc Dis 2020 Dec 15;29(12):105348. Epub 2020 Oct 15.

Department of Neurology, Nitobe Memorial Nakano General Hospital, 4-59-16, Chuo, Nakano-ku, Tokyo 164-8607, Japan.

Herein, we report abdominal aortic thrombosis as a rare cause of acute spinal cord infarction. A 78-year-old man with multiple vascular risk factors developed acute paraplegia with sensory and urinary disturbances and signs of ischemia in both lower limbs. The post-mortem study done 3 days after the onset of symptoms revealed a large coagulum in the abdominal aorta, distal to the renal arteries and extending to bilateral common iliac arteries; in addition, marked atherosclerosis was present in most large blood vessels. Premature incomplete necrotic foci were seen in the ventral gray matter of the spinal cord from T6 through S5; the surrounding white matter and dorsal gray matter were spared. Considering our autopsy case, spinal cord gray matter may be more vulnerable to ischemia than the white matter.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105348DOI Listing
December 2020

Disseminated Bacillus Calmette-Guérin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review.

BMC Infect Dis 2020 Sep 29;20(1):708. Epub 2020 Sep 29.

Department of Neurology, Nitobe Memorial Nakano General Hospital, 4-59-16 Chuo Nakano-ku, Tokyo, 164-8607, Japan.

Background: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.

Case Presentation: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.

Conclusions: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.
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http://dx.doi.org/10.1186/s12879-020-05396-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523392PMC
September 2020

Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?

Endocr Pathol 2021 Jun 23;32(2):262-268. Epub 2020 Sep 23.

Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan.

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous β-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.
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http://dx.doi.org/10.1007/s12022-020-09644-zDOI Listing
June 2021

High amplification of PVT1 and MYC predict favorable prognosis in early ovarian carcinoma.

Pathol Res Pract 2020 Nov 16;216(11):153175. Epub 2020 Aug 16.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.

Introduction: The objective of this study was to evaluate the status of MYC and PVT1, which are frequently amplified in malignant tumors, and to assess their biological features according to histological subtypes in early-stage epithelial ovarian cancer (EOC).

Methods: Formalin-fixed and paraffin-embedded (FFPE) samples of 64 EOC tissues in International Federation of Gynecology and Obstetrics stages I-II and 20 normal ovarian tissues were analyzed for copy number and mRNA expression of MYC and PVT1 by qPCR and for MYC protein expression by immunohistochemistry. MYC protein expression was assessed by western blotting in a PVT1 siRNA-transfected ovarian cancer cell line. MYC and PVT1 was assessed as a prognostic factor using Kaplan-Meier analysis. The median follow-up period was 49.9 months and 17 cases in 64 of EOC recurred during follow-up.

Results: Copy number variations showed significantly higher MYC and PVT1 in EOC than in normal ovaries. The copy number of PVT1 was significantly higher in serous carcinoma than in the other histological types. The mRNA of MYC and PVT1 was also higher in cancer tissues and showed a strong correlation in all histological subtypes. Immunohistochemistry revealed a positive association between the phosphorylated MYC (pMYC) index and high expression of proliferation markers, such as Ki-67 index, and a negative correlation between pMYC protein and the PVT1 copy number. Knockdown of PVT1 in ovarian cancer cell lines resulted in upregulation of MYC protein and pMYC. Kaplan-Meier survival analysis showed that low copy numbers of both MYC and PVT1 were associated with a statistically significantly poor prognosis.

Conclusion: Expression of pMYC and the Ki-67 index were affected by the PVT1 copy number but not mRNA. A high PVT1 copy number in FFPE samples might suggest favorable prognosis in early ovarian cancers.
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http://dx.doi.org/10.1016/j.prp.2020.153175DOI Listing
November 2020

Clinicopathological and molecular analysis of SIRT7 in hepatocellular carcinoma.

Pathology 2020 Aug 22;52(5):529-537. Epub 2020 Jun 22.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address:

Sirtuin 7 (SIRT7) is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase that is reported to contribute to tumour growth and invasion by selectively acting on histone H3K18. It is overexpressed in several cancers including hepatocellular carcinoma (HCC). In this study, we investigated the relationship between SIRT7 expression, proliferation (Ki-67 index) in human HCC tissues, and patient prognosis. We analysed 219 HCC samples obtained retrospectively, for clinicopathological features, and with immunohistochemistry. SIRT7 overexpression was observed in 73 cases (33%) and correlated with vascular invasion and poor differentiation of HCC. Ki-67 labelling index was observed to be significantly higher in SIRT7 overexpressing cases. Interestingly, the Ki-67 labelling index was higher in SIRT7 overexpressing cases regardless of the differentiation status of HCC. Multivariate analysis demonstrated SIRT7 overexpression as an independent factor predictive of poor prognosis (p=0.016). In vitro, SIRT7 knockdown led to reduced growth in cells and resulted in a lower percentage of G0/G1 cells compared to controls. In addition, the ratio of apoptotic cells following sorafenib treatment was significantly higher in SIRT7 knockdown cells than control cells (p=0.040), implying that SIRT7 knockdown potentiated the effect of sorafenib. In conclusion, our study showed that overexpression of SIRT7 was associated with increased proliferative activity in HCC and predictive of poor prognosis. In addition, our in vitro model showed that SIRT7 knockdown was associated with reduced proliferation, and suggested abrogation of SIRT7 may potentiate the effect of sorafenib. Therefore, we propose that SIRT7 expression by HCC may be used as a prognostic biomarker, and that SIRT7 may be a potential target for new therapeutic modalities.
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http://dx.doi.org/10.1016/j.pathol.2020.03.011DOI Listing
August 2020

Histopathologic Analysis of Signet-ring Cell Carcinoma In Situ in Patients With Hereditary Diffuse Gastric Cancer.

Am J Surg Pathol 2020 09;44(9):1204-1212

Division of Pathology, Cancer Institute.

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Laurén's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P<0.001). To elucidate the specificity of SRCC-pTis for HDGC, 60 samples (range: 0.12 to 1.49 m, total 28.8 m of mucosal length) from gastric cancer cases were analyzed as controls, in which no SRCC-pTis were identified. Our results indicate that SRCC-pTis is a distinct histologic feature with high specificity for HDGC cases with CDH1 germline mutations.
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http://dx.doi.org/10.1097/PAS.0000000000001511DOI Listing
September 2020

Biological activity is not suppressed in mid-shaft stress fracture of the bowed femoral shaft unlike in "typical" atypical subtrochanteric femoral fracture: A proposed theory of atypical femoral fracture subtypes.

Bone 2020 08 26;137:115453. Epub 2020 May 26.

Department of Orthopaedic and Spinal Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Background: We have investigated mid-shaft stress fractures of the bowed femoral shaft (SBFs), well before the first report of an association between suppression of bone turnover and atypical femoral fractures (AFFs). Although all cases of SBF meet the criteria for AFF, SBFs can also occur in patients with no exposure to bone turnover suppression-related drugs (e.g., bisphosphonates). Using bone morphometry and biomechanical analyses, we devised a theory of AFF subtypes, dividing AFFs into fragility SBFs in the mid-shaft and "typical" subtrochanteric AFFs caused by suppressed bone turnover. The aim of this multicenter prospective study was to provide evidence for this novel concept in terms of biological activity.

Methods: The study was conducted at 12 hospitals in Japan from 2015 through 2019. Thirty-seven elderly women with AFF were included and classified according to location of the fracture into a mid-shaft AFF group (n = 18) and a subtrochanteric AFF group (n = 19). Patient demographics and clinical characteristics were investigated to compare the two groups. The main focus was on histological analysis of the fracture site, and bone metabolism markers were evaluated to specifically estimate biological activity.

Results: All patients in the subtrochanteric AFF group had a history of long-term (>3 years) exposure to specific drugs that have been reported to cause AFF, but 5 of the 18 patients in the mid-shaft AFF group had no history of exposure to such drugs. Femoral bowing was significantly greater in the mid-shaft AFF group (p < 0.001). In the histological analysis, active bone remodeling or endochondral ossification was observed in the mid-shaft AFF group, whereas no fracture repair-related biological activity was observed in the majority of patients in the subtrochanteric AFF group. Levels of tartrate-resistant acid phosphatase-5b and undercaroxylated osteocalcin were significantly lower in the subtrochanteric AFF group (p < 0.05).

Conclusion: The possibility of our devised AFF subtype theory was demonstrated. Biological activity tends not to be suppressed in mid-shaft SBFs unlike in "typical" subtrochanteric AFFs involving bone turnover suppression. Although validation of the proposed theory in other populations is needed, we suggest that the pathology and treatment of AFFs be reconsidered based on its subtype.
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http://dx.doi.org/10.1016/j.bone.2020.115453DOI Listing
August 2020

Expression of cathepsins B, D and K in thymic epithelial tumours.

J Clin Pathol 2021 Feb 28;74(2):84-90. Epub 2020 May 28.

Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Aim: Cathepsins are proteases that regulate a wide range of physiological processes, including protein turnover, cell signalling and antigen presentation. Recent studies have shown that cathepsins are highly upregulated in many types of tumours. Of the 15 cathepsins in humans, cathepsins V and S are abundantly expressed in the thymus, and we previously showed that the immunostaining of these cathepsins could serve as diagnostic markers for thymic epithelial tumours. However, little is known about the expression of other cathepsins in thymic epithelial tumours. To determine the diagnostic implications of cathepsins, we performed immunohistochemical analysis of cathepsin B (CTB), cathepsin D (CTD) and cathepsin K (CTK), all of which have been reported to correlate with the progression of squamous cell carcinoma.

Methods: The association between cathepsin expression and clinicopathological features was evaluated in 122 cases of thymoma and thymic carcinoma.

Results: CTB and CTD were frequently expressed in type A and type AB thymomas. In contrast, CTB and CTD were significantly less common in type B thymomas than in type A or AB thymomas. In type AB thymomas, the expression of CTB correlated with histological features, and was found predominantly in the type A component. Notably, CTK was expressed most commonly in thymic carcinomas, and patients who died of the disease showed increased expression of CTK.

Conclusions: The expression of CTB and CTD correlated with the histological subtype of thymoma. In addition, the expression of CTK appears to be useful for the diagnosis of thymic carcinomas and as a prognostic marker.
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http://dx.doi.org/10.1136/jclinpath-2020-206551DOI Listing
February 2021

CRISPR screening identifies M1AP as a new MYC regulator with a promoter-reporter system.

PeerJ 2020 6;8:e9046. Epub 2020 May 6.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Background: is one of the proto-oncogenes contributing to tumorigenesis in many human cancers. Although the mechanism of regulation is still not fully understood, learning about the comprehensive mechanism controlling the transcriptional activity of will lead to therapeutic targets. The CRISPR/Cas9 library system is a simple and powerful screening technique. This study aims to identify new transcriptional upstream activators of using the CRISPR activation library with new promoter-reporter systems.

Methods And Results: The promoter-reporter system was developed with a photoconvertible fluorescent protein, Dendra2, and named "p-promoter-Dendra2." This promoter-reporter system was designed to harbor a proximal promoter at (3.1 kb). Both the CRISPR activation library and p-promoter-Dendra2 were induced to HEK 293T cells, and Dendra2-positive cells, that are supposed that should be upregulated, were collected individually by a cell sorter. Among the 169 cells collected, 12 clones were successfully established. Then, p-promoter-Dendra2 was transfected again into these 12 clones, and two of 12 clones showed Dendra2 positivity. In this procedure, the cells with non-specific autofluorescence were correctly distinguished by utilizing the photoswitchable character of Dendra2. Using extracted genomic DNA of these two Dendra2 positive clones, polymerase chain reaction (PCR) was performed to amplify the guide RNA (gRNA) containing region, which was introduced by the CRISPR activation library. Eventually, , , , and were identified, and these gRNAs were transfected individually into HEK 293T cells again using the CRISPR activation system. Only gRNA transfected cells showed Dendra2-positive fluorescence. Then, the overexpression vector for with a doxycycline-inducible vector confirmed that induced high expression by real-time quantitative PCR and western blot. Furthermore, the dual-luciferase assay showed a significant increase of promoter activity, and mRNA was higher in - overexpressing cells. is highly expressed in several cancers, though, a positive correlation between and was observed only in human acute myeloid leukemia.

Conclusion: The present study confirmed that the experimental method using the CRISPR library technology functions effectively for the identification of molecules that activate endogenous . This method will help elucidate the regulatory mechanism of expression, as well as supporting further drug research against malignant tumors.
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http://dx.doi.org/10.7717/peerj.9046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210806PMC
May 2020

Comorbid argyrophilic grain disease in an 87-year-old male with spinocerebellar ataxia type 31 with dementia: a case report.

BMC Neurol 2020 Apr 15;20(1):136. Epub 2020 Apr 15.

Department of Neurology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Background: Spinocerebellar ataxia type 31 (SCA31) is not usually associated with dementia, and autopsy in a patient with both conditions is very rare.

Case Presentation: An 87-year-old male patient presented with ataxia and progressive dementia. Genetic testing led to a diagnosis of SCA31. Fifteen years after his initial symptoms of hearing loss and difficulty walking, he died of aspiration pneumonia. A pathological analysis showed cerebellar degeneration consistent with SCA31 and abundant argyrophilic grains in the hippocampal formation and amygdala that could explain his dementia.

Conclusions: This is the first autopsy report on comorbid argyrophilic grain disease with SCA31.
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http://dx.doi.org/10.1186/s12883-020-01723-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158122PMC
April 2020

Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra.

Neuropathology 2020 Aug 22;40(4):328-335. Epub 2020 Mar 22.

Department of Neurology, Nitobe Memorial Nakano General Hospital, Tokyo, Japan.

Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB-associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB-associated nuclei. This study on human brains is the first quantitative approach demonstrating MB-associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age-related decline of ubiquitin-proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age-related decline of neural activity in the substantia nigra.
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http://dx.doi.org/10.1111/neup.12647DOI Listing
August 2020

Clinicopathological Features of Advanced Gastric Cancers which Were Misjudged and Subjected to Endoscopic Submucosal Dissection.

Gastroenterol Res Pract 2020 2;2020:6525098. Epub 2020 Mar 2.

Department of Gastroenterology, Toranomon Hospital, 105-8470 Tokyo, Japan.

Background And Aims: Endoscopic submucosal dissection (ESD) is widely performed for early gastric cancer (EGC). We have sometimes encountered gastric cancer lesions for which ESD was performed and at which pathologically advanced cancer was found. In this study, we performed clinicopathological examination of lesions whose endoscopic diagnosis and pathology differed substantially.

Methods: ESD was performed for 2,194 gastric cancer lesions (1,753 cases) in our institute from April 2005 through March 2015. The vertical margin was positive or status unknown in 51 lesions (2.3%); among these, muscularis propria (MP) or deeper infiltration was identified in 6 lesions from specimens obtained during subsequent surgery. In 1 lesion with MP invasion, the vertical margin was negative. We evaluated the clinicopathological features of these 7 lesions and retrospectively reviewed endoscopic indicators of submucosal invasion for EGC on white light imaging (WLI), narrow-band imaging magnifying endoscopy (NBI-ME), and endoscopic ultrasonography (EUS) performed previously.

Results: Average age was 73.2 ± 7.2 years, and all cases were men. The 7 lesions diagnosed as advanced cancer were 0.32% of 2,194 lesions and were all located in the U region (fundus). On retrospective review of endoscopic findings, 2 of 7 lesions on WBI, 3 of 6 lesions on NBI-ME, and 2 of 5 lesions on EUS met the criteria for indicating submucosal invasion of EGC. No lesions had findings on all 3 modalities.

Conclusion: In rare cases, advanced gastric cancer could not be accurately diagnosed by endoscopy using various modalities. Each case had special characteristics making identification of deep infiltration difficult.
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http://dx.doi.org/10.1155/2020/6525098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071798PMC
March 2020

Numerous ballooned neurons in a 94-year-old man with dementia with Lewy bodies.

J Neurol Sci 2020 05 4;412:116722. Epub 2020 Feb 4.

Department of Neurology, Nitobe Memorial Nakano General Hospital, Japan.

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http://dx.doi.org/10.1016/j.jns.2020.116722DOI Listing
May 2020

Calretinin-expressing lung adenocarcinoma: Distinct characteristics of advanced stages, smoker-type features, and rare expression of other mesothelial markers are useful to differentiate epithelioid mesothelioma.

Pathol Res Pract 2020 Mar 10;216(3):152817. Epub 2020 Jan 10.

Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Pathology, School of Medicine, International University of Health and Welfare, Tokyo, Japan. Electronic address:

Calretinin, a mesothelioma marker, is sometimes expressed in lung cancer, which may complicate the differential diagnosis of mesothelioma. Here, the clinicopathological and immunohistochemical characteristics of calretinin-positive lung cancer were examined to reduce confusion with malignant mesothelioma. Calretinin expression in 307 consecutive cases of lung cancer was evaluated immunohistochemically. Survival was analyzed using the Kaplan-Meier method and log-rank test. Calretinin expression was identified in 67 (22%) tumors, including those with partial and weak expression [15% (37/250) of adenocarcinomas, 54% (25/46) of squamous cell carcinomas, 75% (3/4) of adenosquamous carcinomas, and 29% (2/7) of sarcomatoid carcinomas]. In calretinin-positive adenocarcinoma (n = 37), expression percentages of Wilms tumor-1, podoplanin, thyroid transcription factor-1, and claudin-4 were 6, 3, 52, 82%, respectively, whereas in calretinin-positive squamous cell carcinoma (n = 25) the percentages were 8, 12, 12, 68%, respectively, indicating that other mesothelial markers were only rarely expressed and that claudin-4 expression was common. Although not an independent marker, calretinin expression was associated with a poor prognosis for stage I tumors of adenocarcinoma (p < 0.001) and of all histological subtypes (p < 0.001). In conclusion, calretinin-positive lung tumors share characteristics with those of smokers and advanced stages and can be differentiated from mesothelioma with the use of other mesothelial and epithelial markers.
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http://dx.doi.org/10.1016/j.prp.2020.152817DOI Listing
March 2020

Clinicopathological features of colorectal polyps and risk of colorectal cancer in acromegaly.

Eur J Endocrinol 2020 Mar;182(3):313-318

Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.

Objective: Patients with acromegaly are at increased risk of colorectal polyps. However, their risk of colorectal cancer remains unclear. This study aimed to identify the histopathological features of colorectal polyps in patients with acromegaly and compare their risk of colorectal cancer with that in healthy controls.

Methods: The study participants were 178 patients who underwent Hardy's operation and perioperative colonoscopy at our hospital between April 2008 and September 2016. For the control group, we randomly selected 356 age- and sex-matched patients who underwent colonoscopy at our hospital during the same period. The incidence, size, location, and histology of the colorectal polyps detected were compared between the groups.

Results: Colorectal polyps were detected in 66.8% of the acromegaly group and 24.2% of the control group (P < 0.001). The average number and size of the polyps were 2.44 and 4.74 mm, respectively, in the acromegaly group and 1.77 and 3.89 mm in the control group (P = 0.001). Polyps in the acromegaly group were more likely to be in the rectosigmoid region (P = 0.006). In the acromegaly group, the frequency of polyps ≥5 mm was 34.3% and that for polyps ≥10 mm was 15.2%; the respective values were 7.6% and 2.2% in the control group (P < 0.001). We found no evidence of between-group histopathological differences in the polyp specimens resected by endoscopy.

Conclusions: Patients with acromegaly are at an increased risk of colorectal polyps, especially in the rectosigmoid region. However, there is no pathological evidence that they are at greater risk of colorectal cancer than the general population.
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http://dx.doi.org/10.1530/EJE-19-0813DOI Listing
March 2020

The expression of MYC is strongly dependent on the circular PVT1 expression in pure Gleason pattern 4 of prostatic cancer.

Med Mol Morphol 2020 Sep 13;53(3):156-167. Epub 2020 Jan 13.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

PVT1 is a long-noncoding RNA and is highly expressed in various cancers including prostate cancers with stabilizing MYC protein. To characterize the objective biological features of the different morphological components such as Gleason patterns (GP) in prostate cancer, biopsy specimens containing only single pure GP (GP3, GP4, GP5) are used to analyze the relationship between PVT1 expression and MYC protein expression. The expressions of PVT1 and MYC were analyzed by quantitative PCR and the labeling index (LI) of MYC protein by immunohistochemical staining. PVT1, MYC, and MYC protein were highly expressed in GP 4, and interestingly the expression between PVT1 and MYC LI significantly correlated only in GP 4. In vitro experiments, the expression of MYC protein was slightly reduced by small interfering RNA against PVT1, while strongly reduced against specifically circular PVT1, splicing variants derived from the PVT1. Taken together, the expression characteristics of PVT1, MYC, and MYC protein differed depending on the GP. In particular, circular PVT1 might be strongly involved in the stabilization of MYC protein in GP4 and suggest different biological features.
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http://dx.doi.org/10.1007/s00795-020-00243-9DOI Listing
September 2020

Clinicopathological characteristics of gastric cancer with carbohydrate antigen 19-9 expression occurring in elderly individuals: An autopsy study.

Pathol Int 2020 Feb 23;70(2):92-100. Epub 2019 Dec 23.

Departments of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.

The clinicopathological significance of carbohydrate antigen 19-9 (CA19-9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19-9 in GC utilizing autopsy cases. We examined the expression of CA19-9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19-9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19-9 expression in GC. Compared to GC cases with negative CA19-9 expression (tCA19-9-N), those with positive CA19-9 expression (tCA19-9-P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19-9 levels (sCA19-9-L), those with high serum CA19-9 levels (sCA19-9-H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19-9-P GC and sCA19-9-H GC cases were significantly associated with coagulation abnormalities. sCA19-9-H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19-9 expression in GC. These results suggest that CA19-9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities.
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http://dx.doi.org/10.1111/pin.12882DOI Listing
February 2020

Bone marrow niches in myeloid neoplasms.

Pathol Int 2020 Feb 10;70(2):63-71. Epub 2019 Nov 10.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Pathological phenotypes of myeloid neoplasms are closely related to genetic/chromosomal abnormalities of neoplastic cells whereas the bone marrow microenvironment, including stromal elements and hematopoietic stem cell niche cells, have a great influence on the differentiation/proliferation of both hematopoietic and neoplastic cells. The pathology of myeloid neoplasms might be generated through the interaction of hematopoietic (stem) cells and stromal cells. The present study aims to provide the morphological/functional aspects of the bone marrow environment in myeloid neoplasms. Among the myeloid neoplasms, myelodysplastic syndromes (MDS) exhibit significant and complex interactions between neoplastic cells and stromal cells. Hematopoietic cells in MDS are greatly influenced by macrophages/niche cells via several signaling pathways. As such, the pathological significance of cell proliferation, cell apoptosis, and anti-apoptosis signals in the bone marrow of myeloid neoplasms, especially MDS bone marrow, will be discussed.
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http://dx.doi.org/10.1111/pin.12870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232432PMC
February 2020

Fatty acid beta oxidation enzyme HADHA is a novel potential therapeutic target in malignant lymphoma.

Lab Invest 2020 03 16;100(3):353-362. Epub 2019 Sep 16.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.

Cancer cells, including malignant lymphoma cells, alter their metabolism, termed "metabolic reprograming," on initiation of malignant transformation as well as upon accumulation of genetic abnormalities. Here, to identify a novel therapeutic target involved in the metabolic changes during malignant lymphoma, we performed global analyses combined with shotgun proteomics, in silico database analysis, and clinic-pathologic analysis of nonneoplastic lymphoid tissue and malignant lymphoma tissue and verified the molecular functions in vitro. In total, 2002 proteins were detected from both samples and proteins related to fatty acid beta-oxidation (FAO) were detected more frequently in malignant lymphoma tissue. Consequently, the most frequently detected protein, the mitochondrial trifunctional enzyme subunit-alpha (HADHA), was identified as a potential target. Immunohistochemical analyses revealed that HADHA tended to be overexpressed in a high-grade subtype of malignant lymphoma tissue. Clinicopathologic study revealed that HADHA overexpression was correlated with significantly worse overall survival (P = 0.013) and was an independent prognostic predictor in diffuse large B-cell lymphoma (P = 0.027). In vitro, downregulation of HADHA negatively regulated cell growth by causing G0/G1 arrest (P = 0.0008) similar to treatment with etomoxir, an inhibitor of FAO (P = 0.032). Moreover, downregulation of HADHA increased the susceptibility to doxorubicin (P = 0.002) and etoposide (P = 0.004). Moreover, these phenotypes were confirmed in an HADHA knockout system. Thus, we provide a basis for a novel therapeutic strategy through the regulation of HADHA and FAO in patients with refractory malignant lymphoma.
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http://dx.doi.org/10.1038/s41374-019-0318-6DOI Listing
March 2020

Colorectal cancer risk factors in asymptomatic Chilean population: a survey of international collaboration between Japan and Chile.

Eur J Cancer Prev 2020 03;29(2):127-133

Department of Comprehensive Pathology, Tokyo Medical and Dental University, Tokyo, Japan.

In Chile, the mortality from colorectal cancer has been on the rise. A national screening program based on a fecal immunochemical test was started in 2012 as an international collaboration with Japan. This case-control study was designed to identify the risk factors for colorectal cancer, with a goal of increasing the participation rate for colorectal cancer screening. In accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines, we conducted a case-control study from 2012 to 2017; 23 845 asymptomatic participants were enrolled in the study. Participants who were fecal immunochemical test-positive or had a family history of colorectal cancer underwent a colonoscopy. We analyzed the odds ratio of the risk factors for colorectal cancer, including sex, age, family history, BMI, hypertension, diabetes, regular use of nonsteroidal anti-inflammatory drugs, alcohol consumption, smoking, physical activity, and daily intake of certain food items. For the screening program, 202 cases of colorectal cancer were detected, and 195 of them were evaluated pathologically after resection. Of these, 173 cases (88.7%) had colorectal cancer stage 0/1, 151 (77.4%) of which were treated with endoscopic resection. In the multivariate analysis, male sex, family history of colorectal cancer, and low intake of cereals or fibers were closely related to a high colorectal cancer incidence. Moreover, participants in their 60s and 70s had a higher incidence of colorectal cancer than those in their 50s. These results suggest that intensive screening of the high-risk population can help in improving the detection of colorectal cancer, whereas higher consumption of cereals or fibers can be effective in preventing its onset.
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http://dx.doi.org/10.1097/CEJ.0000000000000531DOI Listing
March 2020

Three-dimensional surface models of autopsied human brains constructed from multiple photographs by photogrammetry.

PLoS One 2019 10;14(7):e0219619. Epub 2019 Jul 10.

Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.

Virtual three-dimensional (3D) surface models of autopsied human brain hemispheres were constructed by integrating multiple two-dimensional (2D) photographs. To avoid gravity-dependent deformity, formalin-fixed hemispheres were placed on non-refractile, transparent acrylic plates, which allowed us to take 2D photographs from various different angles. Photogrammetric calculations using software (ReCap Pro cloud service, Autodesk, San Rafael, CA, USA) allowed us calculate the 3D surface of each brain hemisphere. Virtual brain models could be moved and rotated freely to allow smooth, seamless views from different angles and different magnifications. When viewing rotating 3D models on 2D screens, 3D aspects of the models were enhanced using motion parallax. Comparison of different brains using this method allowed us to identify disease-specific patterns of macroscopic atrophy, that were not apparent in conventional 2D photographs. For example, we observed frontal lobe atrophy in a progressive supranuclear palsy brain, and even more subtle atrophy in the superior temporal gyrus in amyotrophic lateral sclerosis-frontotemporal lobar degeneration. Thus, our method facilities recognition of gyral atrophy. In addition, it provides a much more powerful and suitable way of visualizing the overall appearance of the brain as a three-dimensional structure. Comparison of normal and diseased brains will allow us to associate different macroscopic changes in the brain to clinical manifestations of various diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219619PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619815PMC
February 2020

Subtypes of Breast Cancer in Lao P.D.R.: A Study in a Limited-Resource Setting

Asian Pac J Cancer Prev 2019 Feb 26;20(2):589-594. Epub 2019 Feb 26.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Aim: The purpose of this study is to evaluate the prevalence of the immunohistochemical subtypes of breast cancer among Lao women by using immunohistochemistry (according to the St. Gallen 2017 guidelines) and to study their correlation to clinicopathological features in order to help guide better treatment plans for patients. Materials and methods: Formalin-fixed and paraffin embedded tissue blocks of 76 cases of primary invasive breast cancer were retrieved from the University of Health Sciences, Vientiane, Lao PDR, from 2013 to 2016. Patients’ information and previous histological reports were reviewed. Immunohistochemistry was done using antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu) and Ki-67 (MIB-1). Results: The mean age of the patients was 49 years, and the major histologic type was invasive ductal carcinoma, NOS (90.7%). The proportion of each subtype was hormone receptor-positive and HER2-negative, 44.7%; hormone receptor-positive and HER2-positive, 3.9%; hormone receptor-negative and HER2-positive, 13.2%; and triple-negative, 38.2%. ER was positive in 40.8% of the cases, while PR was positive in 47.4%. More than half of the cases were poorly differentiated cancer (65.8%), followed by moderately differentiated (34.2%). Tumors presented with pT2 (60.5%), followed by pT3 (25.0%) and pT4 (7.9%). Conclusion: Breast cancer among Lao women is characterized by a large percentage of the triple-negative subtype that is less susceptible to hormonal treatments. The empirical treatment with tamoxifen should be reconsidered since it would be less effective to these patients. More importantly, basic pathology services should be the first requirement in Lao PDR in order to provide adequate care.
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http://dx.doi.org/10.31557/APJCP.2019.20.2.589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897003PMC
February 2019

Useful Application of Immunostaining to Malignant Pleural Effusion among Lao People in Vientiane Capital, Lao PDR

Asian Pac J Cancer Prev 2019 Jan 25;20(1):243-248. Epub 2019 Jan 25.

Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. Email:

Background: Pathology and laboratory medicine (PALM) services are limited in low-resource countries, such as Lao PDR. Patients with malignant pleural effusion (MPE) are not properly diagnosed and treated in these situations. The purpose of this study is to confirm the usefulness of immunocytochemistry in MPE to identify the histological type and probable primary site of cancer of MPE and to discuss its usefulness in low-resource countries, such as Laos. Methods: We retrospectively reviewed glass slides of pleural effusion sent to the Department of Pathology at the University of Health Sciences from the central hospitals for cytological screening from January 2012 to December 2016. The cytological review, cell transfer and immunocytochemical staining were performed at Tokyo Medical and Dental University. Among 81 cases of MPE from Laos, 66 cases of malignant tumors that contained enough tumor cells were included in this study, and the slides were screened with 14 primary antibodies to classify the histological type and identify the probable primary site of carcinoma. Results: Among the 66 cases, 34 cases (52%) were of female patients, and 32 cases (48%) were of male patients. The patients’ ages ranged from 28 to 88 years with an average of 58 years. The immunocytochemical study identified 32 cases (49%) of primary lung adenocarcinoma, two cases (3%) of malignant mesothelioma, one case (1.5%) of breast/gynecological carcinoma, one case (1.5%) of T cell lymphoma, and one case (1.5%) of B cell lymphoma. Twenty-nine cases (43.5%) were classified as carcinoma not otherwise specified. Pulmonary small cell carcinoma/squamous cell carcinoma and metastatic colon, prostate, and liver carcinoma were not identified among the cases. Conclusions: Immunocytochemistry is a useful ancillary method in MPE diagnostics. This method could be applied in the pathological laboratories in low- or middle-resource countries, such as Laos.
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http://dx.doi.org/10.31557/APJCP.2019.20.1.243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485547PMC
January 2019