Publications by authors named "Mitsumasa Osakabe"

51 Publications

Coexistence of salivary duct, myoepithelial and epithelial-myoepithelial carcinomas in the parotid gland: a case report and literature review.

J Surg Case Rep 2021 Jun 4;2021(6):rjab230. Epub 2021 Jun 4.

Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate Japan.

Few reports have described two or more histologically-distinct carcinoma types within the same salivary gland. A 62-year-old man presented to our hospital after detecting a mass in the right parotid gland. Computed tomography revealed a tumor (5.1 × 5.0 cm) within the right parotid gland. Tumor resection with lymph node dissection was performed. The proliferation of three morphologically-different tumor cells was demonstrated on histopathologic examination (salivary duct carcinoma [SDC], myoepithelial carcinoma and epithelial-myoepithelial carcinoma [EMC]). The shape of the inner layer of cells in the EMC was similar to the SDC. Specifically, it appeared that the cells were a mixture of the two tumors with reciprocal transfer in the same area. Immunohistochemical staining showed that the SDC cells and the EMC inner cells were positive for AR, HER2 and p53. Thus, we suggest that our case represented a high-grade transformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jscr/rjab230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177961PMC
June 2021

SMARCB1-deficient sinonasal carcinoma: a case report and literature review.

J Surg Case Rep 2021 Apr 30;2021(4):rjab161. Epub 2021 Apr 30.

Departments of Molecular Diagnostic Pathology, Yahaba-cho, Shiwa-gun, Iwate, Japan.

SWItch/Sucrose Non-Fermentable (SWI/SNF) -related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) deficient sinonasal carcinoma (SdSNC) is a rare variant of sinonasal undifferentiated carcinoma (SNUC). A 72-year-old man was referred to our hospital with complaints of left facial pain and nasal obstruction. Computed tomography (CI) revealed a tumor 5.5 cm in size in the left nasal cavity. Atypical cells with eosinophilic cytoplasm proliferating as solid nests and exhibiting necrosis were observed and diagnosed as poorly differentiated carcinoma. Carbon ion radiotherapy was performed. Follow-up CI revealed multiple masses in both lungs. Partial resection of the right lung was performed. Proliferating atypical cells with clear-to-eosinophilic cytoplasm were observed and resembled those in the paranasal sinus tumor. Immunohistochemical analysis indicated a metastatic lung tumor derived from the SNUC revealed completely negative SMARCB1 expression in the nuclei of the tumor cells. SdSNC is difficult to diagnose. However, molecular targeted therapy may be useful. Thus, it is necessary and important to recognize this rare cancer accurately.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jscr/rjab161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088288PMC
April 2021

Microenvironmental markers are correlated with lymph node metastasis in invasive submucosal colorectal cancer.

Histopathology 2021 Apr 21. Epub 2021 Apr 21.

Division of Gastroenterology, Department of Internal Medicine, 2-1-1, Shiwagun'yahabachou, 028-3695, Japan.

Aims: Recent studies have shown that the microenvironment can include cancer cells and cancer-associated fibroblasts (CAFs) and that both play important roles in the progression and metastasis of CRC. Here, we aimed to analyze the expression patterns of cancer cell- and CAF-related proteins in submucosal invasive colorectal cancer (SiCRC) and whether such markers are correlated with lymph node metastasis (LNM).

Methods And Results: Quantitative analysis was conducted for Ki-67, p53, β-catenin, and MMP7 to assess cancer cell markers. In addition, we examined CAF markers, including α-SMA, CD10, podoplanin, FSP-1, PDGF-α, PDGF-β, AEBP1, FAP-1, ZEB1 and TWIST1. In both cases, we conducted digital pathology with Aperio software. We also examined the expression patterns of biomarkers using hierarchical cluster analysis. Two subgroups were established based on the expression patterns of cancer cell- and CAF- related markers, and the associations of these subgroups with clinicopathological variables. In multivariate analysis, subgroup 2, which was characterized by high expression of Ki-67, p53, FAP-1, PDGF α, PDGF β, and TWIST1, was correlated with LNM (p < 0.01). Next, we examined the associations of individual biomarkers with LNM. Multivariate analysis showed that high expression levels of Ki-67 and FA1 were significantly associated with LNM (p < 0.05).

Conclusions: Our findings showed that expression patterns of cancer cell- and CAF related proteins may allow for stratification of patients into risk categories for LNM in SiCRC. In addition, Ki-67- and FAP-1-expressing microenvironmental cells might be helpful for identification of correlations with LNM in SiCRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14388DOI Listing
April 2021

Undifferentiated carcinoma arising from intracranial epidermoid cyst.

Pathol Int 2021 Apr 9;71(4):281-283. Epub 2021 Feb 9.

Departments of Molecular Diagnostic Pathology, Iwate Medical University, Iwate, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.13071DOI Listing
April 2021

A genome-wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors.

Genes Chromosomes Cancer 2021 Apr 24;60(4):250-262. Epub 2020 Dec 24.

Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome-wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22-q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gcc.22924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898915PMC
April 2021

Programmed death ligand 1 protein expression is positively correlated with the solid predominant subtype, high MIB-1 labeling index, and p53 expression and negatively correlated with epidermal growth factor receptor mutations in lung adenocarcinoma.

Hum Pathol 2021 Feb 5;108:12-21. Epub 2020 Nov 5.

Department of Molecular Diagnostic Pathology, Iwate Medical University, Shiwa-gun, Iwate, 0283695, Japan.

Programmed death ligand 1 (PD-L1) protein expression is a proposed predictive biomarker of immunotherapy; thus, identification of the clinicopathological and molecular characteristics associated with PD-L1 expression is important and necessary. We examined PD-L1 immunohistochemical expression and its relationships with the clinicopathological and molecular characteristics of patients with surgically resected nonsmall cell lung carcinoma. PD-L1 expression differed according to the histological subtype. Among 633 patients with adenocarcinoma, 523 (82.6%) had no PD-L1 expression, 78 (12.3%) low expression, and 32 (5.1%) high expression. PD-L1 expression was more common in men (p < 0.001), in smokers (p = 0.002), and in patients with a more advanced stage (p = 0.002), the solid predominant subtype (p < 0.001), no epidermal growth factor receptor(EGFR) mutations (p < 0.001), a high MIB-1 labeling index (p < 0.001), and positive p53 immunohistochemical expression (p < 0.001). In a multivariate logistic regression analysis, the solid predominant subtype (odds ratio [OR] = 4.92, 95% confidence interval [CI]: 2.72-8.89, p < 0.001), no EGFR mutations (OR = 2.27, 95% CI: 1.35-2.7, p = 0.002), a high MIB-1 labeling index (OR = 2.78, 95% CI: 1.72-4.55, p < 0.001), and p53 positivity (OR = 2.13, 95% CI: 1.34-4.36, p = 0.042) were significantly and independently associated with PD-L1 expression. The combination of the solid predominant subtype with a high MIB-1 labeling index was strongly associated with positive expression of PD-L1. In the 193 patients with squamous cell carcinoma, 92 (47.7%) had no PD-L1 expression, 57 (29.5%) low expression, and 44 (22.8%) high expression. There were no significant correlations between PD-L1 expression and the evaluated clinicopathological or molecular characteristics of these patients. These results, indicating associations of PD-L1 with various clinicopathological or molecular characteristics in adenocarcinoma but not squamous cell carcinoma, may be useful for selecting patients with a good response to immune checkpoint inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2020.10.014DOI Listing
February 2021

Genome-wide analysis of microRNA to evaluate prognostic markers in isolated cancer glands and surrounding stroma in high-grade serous ovarian carcinoma.

Oncol Lett 2020 Dec 8;20(6):338. Epub 2020 Oct 8.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Yahaba, Iwate 028-3695, Japan.

The molecular mechanisms responsible for the progression of ovarian cancer remain incompletely understood. By targeting multiple cancer-related genes, microRNAs (miRNAs) have been identified as key regulators of cancer development and progression. In addition, the microenvironment, which constitutes cancer glands and the surrounding stromal tissue at the invasive front, has an important role in cancer progression. Using array-based analysis of 14 cases (cohort 1), the aim of the present study was to evaluate global miRNA expression in cancerous glands and surrounding stromal tissues (isolated using a crypt isolation method), in order to identify potential prognostic markers of high-grade serous carcinoma (HGSC). Reverse transcription-quantitative PCR was also used to verify the results in cohort 1 (14 cases) and in 16 additional HGSC cases (cohort 2; verification cohort). Firstly, miRNA expression levels were compared between HGSC and normal samples among both the isolated cancer gland and stromal tissue samples. Secondly, miRNA expression was compared between HGSC cases with recurrence and those without recurrence among the isolated cancer gland and stromal tissue samples. The results revealed six and seven miRNAs identified in both of the aforementioned comparisons in isolated cancer glands and surrounding stromal tissue, respectively. Furthermore, downregulation of miRNA-214-3p in isolated cancer glands and downregulation of miRNA-320c in the corresponding stromal tissue were associated with a decrease in disease-free survival (without recurrence) in cohort 2. These findings indicated that specific miRNAs expressed in cancer cells and surrounding stromal cells of HGSC may be potential biomarkers predicting patient prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2020.12198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583725PMC
December 2020

Immunohistochemical Analysis of Mismatch Repair Gene Proteins in Early Gastric Cancer Based on Microsatellite Status.

Digestion 2020 Oct 14:1-10. Epub 2020 Oct 14.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Shiwa, Japan,

Background: Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis and is observed in 10-20% of early gastric cancers (EGCs). Early detection of EGCs with an MSI-high phenotype would be useful for elucidating the mechanisms of gastric carcinogenesis and improving outcomes in patients with GC.

Objective: We explored the usefulness of immunohistochemical expression of mismatch repair (MMR) proteins, including MLH1, PMS2, MSH2, and MSH6 in EGC.

Methods: We examined the expression of 4 MMR proteins using immunohistochemistry in 119 patients with EGC based on MS status, as determined by polymerase chain reaction-microsatellite analysis. In addition, methylation of the MLH1 gene was quantified by pyrosequencing.

Results: EGCs were classified into 46 MSI-high phenotypes and 73 microsatellite stable (MSS) phenotypes. Although loss of MLH1 expression was associated with loss of PMS2 expression in the MSI-high phenotype, discordant cases of loss of expression between MLH1 and PMS2 were found (MLH1 [-]/PMS2 [+], 3 cases). Loss of MLH1/PMS2 expression was observed in 2 of 73 MSS phenotypes. Loss of MSH2/MSH6 expression was found in 4 of 46 MSI-high phenotypes, whereas loss of MSH2/MSH6 expression was not detected in the MSS phenotype. In addition, loss of MLH1 expression was correlated with methylation of MLH1. However, there were discordant cases in which loss of MLH1 expression was not accompanied by methylation of MLH1.

Conclusion: Although immunostaining of MMR proteins could help predict MSI in EGCs, immunostaining did not have the same value as genetic testing for determination of MSI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510679DOI Listing
October 2020

Epiploic appendage infarction of the sigmoid colon.

Pathol Int 2020 Nov 14;70(11):918-919. Epub 2020 Sep 14.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Iwate, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.13019DOI Listing
November 2020

Pulmonary epithelial-myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations: a case report.

Diagn Pathol 2020 Aug 28;15(1):105. Epub 2020 Aug 28.

Department of Molecular Diagnostic Pathology, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 0283695, Japan.

Background: Pulmonary epithelial-myoepithelial carcinoma is a rare subtype of lung cancer. Because of its rarity, the molecular information on this carcinoma is insufficient.

Case Presentation: We report a case of pulmonary epithelial-myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations in a 76-year-old woman. Computed tomography revealed a tumor located in the left lower lung. Thoracoscopic left lower lobectomy was performed. Histopathologically, the tumor consisted of duct-like structures and polygonal and spindle cell features. The duct-like structures were composed of two distinct cell layers. The inner layer consisted of cuboidal cells that were positive for pan-cytokeratin and negative for p63, whereas the outer layer consisted of polygonal and spindle cells that were positive for p63 and weakly positive for pan-cytokeratin. We evaluated mutations in AKT1, BRAF, CTNNB1, HRAS, KRAS and PIK3CA but did not detect any mutations.

Conclusion: Pulmonary epithelial-myoepithelial carcinoma is a rare subtype of lung cancer, with only 56 previous cases reported in the English literature. The genetic alterations in pulmonary epithelial-myoepithelial carcinoma are still unknown. We examined the 6 genes mutation analysis, however no mutation was detected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13000-020-01020-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456004PMC
August 2020

Dysregulation of microRNA expression during the progression of colorectal tumors.

Pathol Int 2020 Sep 26;70(9):633-643. Epub 2020 Jun 26.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Iwate, Japan.

MicroRNAs (miRNAs) are potential biomarkers of neoplastic lesions, but additional information on dysregulated miRNA expression during progression of the adenoma-adenocarcinoma sequence may be helpful to identify the role of miRNAs in this sequence. We examined the expression levels of 13 miRNAs (hsa-miRNA-19a-3p, hsa-miRNA-21-5p, hsa-miRNA-27a-3p, hsa-miRNA-27b-3p, hsa-miRNA-31-5p, hsa-miRNA-34b-3p, hsa-miRNA-125b-5p, hsa-miRNA-143-3p, miRNA-191-5p, hsa-miRNA-193b-3p, hsa-miRNA-195-5p, hsa-miRNA-206 and hsa-let-7a-5p) that are closely associated with colorectal carcinogenesis in 40 conventional adenomas (tubular and tubulovillous adenomas), 20 intramucosal carcinomas (IMCs) and 60 invasive colorectal cancers (iCRCs) using reverse-transcription polymerase chain reaction. These 120 tumors were divided into two cohorts, that is, cohort 1 (60 cases) and cohort 2 (for validation; 60 cases). We analyzed the expression levels of these miRNAs in the first step (adenoma→IMC) and second step IMC→iCRC) of the adenoma-carcinoma sequence in both cohorts. Although no significant differences in the expression of any of the 13 miRNAs were found between adenomas and IMCs consistently in both cohorts, the expression levels of hsa-miRNA-125b-5p, hsa-miRNA-143-3p, and hsa-miRNA-206 were significantly upregulated in iCRC in both cohorts compared with those in IMC. The current results suggest that certain miRNAs, including hsa-miRNA-125b-5p, hsa-miRNA-143-3p and hsa-miRNA-206, are candidate markers that play critical roles in the progression of IMC to iCRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.12975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540039PMC
September 2020

The clinicopathological and molecular features of sporadic gastric foveolar type neoplasia.

Virchows Arch 2020 Dec 12;477(6):835-844. Epub 2020 Jun 12.

Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou, 028-3695, Japan.

Gastric intraepithelial foveolar type neoplasia (IEFN) is not well defined. In addition, atrophic mucosa (AM) is an important issue to consider when evaluating gastric tumorigenesis. Here, we assessed the clinicopathological characteristics and molecular alterations contributing to the development of IEFN compared with intestinal type neoplasia. We examined the clinicopathological and molecular features of 42 cases of IEFN with low-grade dysplasia (LGD) and those of 77 cases of intraepithelial intestinal type neoplasia (IEIN) with LGD. The clinicopathological and molecular features examined included the AM status, mucin phenotype expression, CDX2 expression, p53 overexpression, β-catenin intranuclear accumulation, microsatellite instability (MSI), DNA methylation status (low methylation epigenotype [LME], intermediate ME, or high ME), allelic imbalances (AIs), and APC promoter 1B mutations. There were no differences in the frequencies of AM and rates of CDX2 expression between IEFN and IEIN cases. Although no differences in the frequencies of p53 overexpression and MSI were observed between the two histological types, intranuclear expression of β-catenin was significantly higher in IEIN than in IEFN. In addition, although the rate of LME was significantly higher in IEFN cases than in IEIN cases, IEFN was characterized by AIs at multiple foci. Finally, mutation of the APC promoter 1B, which is a characteristic of gastric adenocarcinoma and proximal polyposis of the stomach (potentially resembling IEFN), was detected in only one IEFN case. These findings suggested that IEFN may be an independent entity in terms of molecular alterations including the presence of multiple AIs and LME.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-020-02846-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683467PMC
December 2020

Eosinophilic esophagitis with a severe stenosis: report of a Japanese case.

Clin J Gastroenterol 2020 Oct 8;13(5):708-712. Epub 2020 Jun 8.

Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Idaidori 1-1-1, Yahaba, 028-3694, Japan.

A 49 years old male, who had had postprandial dysphagia during the preceding 10 years, was referred to our hospital. Esophagogastroduodenoscopy (EGD) revealed longitudinal furrows and concentric rings in the mid to lower esophagus and stenosis in the lower esophagus. Histologic findings from esophageal biopsies showed eosinophilic infiltration (> 15 per high-power field). Under a diagnosis of eosinophilic esophagitis, an endoscopic bougie was performed, which resulted in symptomatic relief. Follow-up EGD revealed that the stenosis had improved, but histologic findings of eosinophilic esophagitis were remaining. Our case suggests that although rare, esophageal stenosis occurs in Japanese patients with EoE, and that the complication may be a consequence of prolonged disease. Other risks and the appropriate treatment for the prevention of stenosis need to be elucidated further.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12328-020-01145-0DOI Listing
October 2020

Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma.

Mol Carcinog 2020 04 10;59(4):412-424. Epub 2020 Feb 10.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.

Somatic copy number alterations (SCNAs) are important biological characteristics that can identify genome-wide alterations in renal cell carcinoma (RCC). Recent studies have shown that SCNAs have potential value for determining the prognosis of RCC. We examined SCNAs using the Affymetrix platform to analyze samples from 59 patients with clear cell RCCs (ccRCCs) including first cohort (30 cases) and second cohort (validation cohort, 29 cases). We stratified SCNAs in the ccRCCs using a hierarchical cluster analysis based on SCNA types, including gain, loss of heterozygosity (LOH), copy neutral LOH, mosaic, and mixed types. In this way, the examined two cohorts were categorized into two subgroups (1 and 2). Although the frequency of mixed type was higher in subgroup 1 than in subgroup 2 in the two cohorts, the association did not reach statistical significance. There was a significant difference in the frequency of metachronous metastasis between subgroups 1 and 2 (subgroup 2 > 1). In addition, subgroup 2 was retained in multivariate analysis of both cohorts. We examined whether there were specific alleles differing between subgroups 1 and 2 in both cohorts. We found that there was indeed a statistically significant difference in the 3p mixed types. Among the 3p mixed type, we found that 3p24.3 mixed type was inversely correlated with the presence of metachronous metastasis in ccRCC. The association was also retained in multivariate analysis in second cohort. We suggest that the 3p24.3 mixed type may be a novel marker to predict a favorable prognosis in ccRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.23164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079091PMC
April 2020

Sarcomatoid change associated with epithelial-mesenchymal transition in mucinous tubular and spindle cell carcinoma of the kidney: a case report.

Int J Clin Exp Pathol 2019 1;12(7):2767-2771. Epub 2019 Jul 1.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University 19-1, Morioka 020-8505, Japan.

We report an unusual case of mucinous tubular and spindle cell carcinoma (MTSCC) with sarcomatoid change in an 80-year-old Japanese male. In a resected specimen, a grayish-white tumor was found in the left kidney, and several metastases were observed in the right cervical bone and liver. Histologically, most of the main tumor examined showed MTSCC with sarcomatoid change. The transitions between the MTSCC and sarcomatoid components suggested that sarcomatoid transformation had occurred in the MTSCC. Immunohistochemically, the epithelial-mesenchymal transition (EMT)-associated marker ZEB1 was expressed in the sarcomatoid and transitional components. In contrast, ZEB1 expression was negative in the MTSCC component. The present findings support the view that MTSCC with sarcomatoid change represents MTSCC that develops a sarcomatoid component via EMT of the MTSCC component. EMT plays an important role in sarcomatoid change; thus, we conclude that MTSCC with sarcomatoid change is an 'EMT associated tumor'.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949544PMC
July 2019

Multi-institutional re-evaluation of prognostic factors in chromophobe renal cell carcinoma: proposal of a novel two-tiered grading scheme.

Virchows Arch 2020 Mar 23;476(3):409-418. Epub 2019 Nov 23.

Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland.

A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-019-02710-wDOI Listing
March 2020

Classic Chromophobe Renal Cell Carcinoma Incur a Larger Number of Chromosomal Losses Than Seen in the Eosinophilic Subtype.

Cancers (Basel) 2019 Oct 3;11(10). Epub 2019 Oct 3.

Department of Pathology and Molecular Pathology, University and University Hospital Zurich, CH-8091 Zurich, Switzerland.

Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC ( < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11101492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826417PMC
October 2019

The expression of gastrointestinal differentiation markers in extrahepatic cholangiocarcinoma: clinicopathological significance based on tumor location.

Hum Pathol 2019 10 8;92:91-100. Epub 2019 Aug 8.

Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Iwate 020-8505, Japan. Electronic address:

The expression of gastrointestinal differentiation markers is associated with the tumorigenesis and prognosis of digestive cancers. However, little is known about the significance of gastrointestinal differentiation marker profiles in patients with extrahepatic cholangiocarcinoma (CCA), which is classified as perihilar and distal CCA. The purpose of this study was to clarify the role of gastrointestinal differentiation marker expression in extrahepatic CCA based on tumor location. We examined the expression of gastrointestinal differentiation markers in resected perihilar (n = 30) and distal (n = 54) CCAs based on the immunohistochemical expression of the following markers: MUC2, MUC5AC, MUC6, CD10, CDX-2, and cytokeratin 20. Expression scores were determined semiquantitatively based on the rate of positively stained cells. Furthermore, we performed hierarchical clustering of the CCAs based on the immunohistochemical expression scores to evaluate differences in the expression patterns of the 6 gastrointestinal differentiation markers. Consequently, perihilar and distal CCAs were stratified into 2 subgroups each. Among the perihilar CCAs, subgroup 1 was characterized by lower expression of MUC5AC and MUC6, a larger median tumor size, and a significantly worse prognosis compared with subgroup 2. Furthermore, the immunohistological subgroup (subgroup 1 versus 2) and TNM stage (stage III versus II) were independent predictors of patient survival. Among the distal CCAs, subgroup 1 was characterized by lower expression of MUC5AC compared with subgroup 2. We suggest that gastrointestinal differentiation marker profiles are useful for stratifying perihilar and distal CCAs. In addition, gastrointestinal differentiation markers play a crucial role in tumor development, particularly in perihilar CCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2019.08.002DOI Listing
October 2019

A Case of Cisternal Pilocytic Astrocytoma Diagnosed with the Balanced Steady-State Free Precession Sequence for Magnetic Resonance Imaging: A Rare Cause of Subarachnoid Hemorrhage.

World Neurosurg X 2019 Jan 17;1:100003. Epub 2018 Dec 17.

Department of Neurosurgery, Iwate Prefectural Chubu Hospital, Kitakami, Iwate, Japan.

Objectives: In approximately 15% of cases of spontaneous subarachnoid hemorrhage (SAH), an obvious source of bleeding cannot be identified by angiography; these are considered cases of SAH of unknown etiology. A rare case of cisternal pilocytic astrocytoma (PA) presenting with SAH is reported. The usefulness of the balanced steady-state free precession (bSSFP) sequence for magnetic resonance imaging (MRI) to detect small cisternal lesions is discussed.

Case Description: The case of a 73-year-old woman who developed repeated SAHs owing to a cisternal PA is presented. She experienced sudden onset of headache and vomiting, and brain computed tomography showed diffuse SAH, whereas angiography demonstrated normal vasculature. Follow-up imaging, including T1-weighted, T2-weighted, T1-weighted contrast-enhanced, and diffusion-weighted MRI, did not show any parenchymal or cisternal lesions, although computed tomography and fluid-attenuated inversion recovery MRI showed SAH in the same region. In contrast, the bSSFP sequence, taken as a different sequence on the same day, showed mixed-intensity reticular lesions in the left basal cistern, while neither hematoma nor positive findings were identified with the other sequences. Based on the radiologic finding and the repeated history of SAH, the lesions were partially removed 2 weeks after onset. Histological examination showed a PA.

Conclusions: Despite being extremely rare, a small cisternal lesion should be considered as a cause of SAH of unknown etiology. The bSSFP sequence may be useful for detecting cisternal lesions that may be missed on the routine MRI sequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wnsx.2018.100003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580896PMC
January 2019

Analysis of Expression Patterns of MicroRNAs That Are Closely Associated With Renal Carcinogenesis.

Front Oncol 2019 31;9:431. Epub 2019 May 31.

Department of Urology, School of Medicine, Iwate Medical University, Morioka, Japan.

MicroRNAs (miRNA) are frequently dysregulated in clear cell renal cell carcinoma (ccRCC). This study aimed to elucidate the role of miRNA expression patterns in renal carcinogenesis and to identify the specific miRNAs that exhibit expression patterns closely associated with patient outcomes. We examined the expression patterns of selected miRNAs, including miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p, miRNA-210-3p, miRNA-141-3p, miRNA-200c-3p, miRNA-135a-5p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p, in 96 samples of ccRCCs using the TaqMan real-time PCR method. In addition, cluster analysis was performed to stratify expression patterns of multiple miRNAs. In the present study, three distinct subgroups could be clearly stratified in ccRCCs. Subgroup 1 was characterized by upregulation of miRNA-155-5p, miRNA-122-5p, miRNA-21-5p, miRNA-185-5p, miRNA-106a-5p, miRNA-106b-3p, miRNA-34b-3p and miRNA-210-3p. Subgroup 2 was closely associated with downregulation of miRNA-141-3p, miRNA200c-3p, miRNA-30a-5p, miRNA-218-5p, miRNA-429, miRNA-200a-3p and miRNA-200b-3p. Moreover, significant lower expression of miRNA-135a-5p was a distinctive feature of subgroup 3, which was correlated with metachronous metastasis. Among the individual markers in subgroup 3, miRNA-135a-5p was retained in multivariate analysis. The cutoff value of miRNA-135a-5p expression to identify the association of an altered level of miRNA-135a-5p with metachronous metastasis in ccRCCs was determined and showed excellent specificity. We suggest that the expression pattern of the chosen miRNAs is useful to identify renal carcinogenesis and to help identify the association of such expression patterns with metachronous metastasis in ccRCCs. In addition, miRNA-135a-5p was an excellent marker for prediction of metachronous metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555129PMC
May 2019

Clinicopathological and Molecular Findings of Differentiated-Type Minute Gastric Intramucosal Neoplasia.

Digestion 2020 3;101(3):287-297. Epub 2019 Apr 3.

Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Morioka, Japan.

Background/aims: To evaluate gastric early differentiate-type carcinogenesis, we attempted to identify clinicopathological and biological differences in differentiated-type minute intramucosal neoplasia (MIMN), which was defined as a tumor with a diameter of < 5 mm.

Methods: We examined clinicopathological findings and biological factors, including TP53 overexpression, mucin phenotype, Ki-67-positive rate, MLH1, intranuclear accumulation of β-catenin, and DNA methylation status (low methylation epigenotype [LME], intermediate methylation epigenotype, and high methylation epigenotype [HME]) in MIMNs. In addition, non-MIMNs were also analyzed. In the present study, MIMN and non-MIMN were also examined based on low-grade dysplasia, high-grade dysplasia, and intramucosal cancer (IMC).

Results: In clinicopathological findings, there were significant differences in sex ratios and tumor locations between MIMNs and non-MIMNs. Among the examined biological factors, no significant differences in the frequencies of biological factors were observed between the 2 intramucosal neoplasia types. However, the frequency of intranuclear accumulation of β-catenin was higher in non-MIMNs than in MIMNs. Finally, although the frequency of HME was significantly lower in MIMNs than in non-MIMNs, the opposite was observed for LME.

Conclusions: The current finding suggested that DNA methylation and accumulation of β-catenin were closely associated with tumor development from MIMN to non-MIMN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000499464DOI Listing
March 2021

[Preoperative Diagnosis of Spinal Immature Teratoma Associated with Cerebrospinal Fluid Leakage from the Congenital Dermal Sinus Tract in a 0-Day-Old Infant:A Case Report].

No Shinkei Geka 2019 Mar;47(3):337-342

Department of Neurosurgery, Iwate Medical University School of Medicine.

We report the case of a patient with spinal immature teratoma and cerebrospinal fluid leakage from the congenital dermal sinus tract. A 0-day-old female infant presented with a subcutaneous soft mass with a dimple in the lumbosacral region at birth. Magnetic resonance imaging revealed a mixed low-intensity mass located in the extraspinal and intraspinal canal with a sinus tract. The reconstructed three-dimensional spinal computed tomography image showed spina bifida and ectopic ossification at the dorsal aspect of the sacrum. Urgent removal of the tumor and dermal sinus tract was then performed under evoked electromyography monitoring. The resected tumor was histopathologically diagnosed as immature teratoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11477/mf.1436203940DOI Listing
March 2019

Mesenteric extraovarian Sertoli-Leydig cell tumor without DICER1 hotspot mutation: a case report.

Diagn Pathol 2019 Apr 1;14(1):27. Epub 2019 Apr 1.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 19-1, Morioka, 020-8505, Japan.

Background: Ovarian Sertoli-Leydig cell tumors (SLCTs) with androgenic manifestations harbor DICER1 mutations in 30-60% of cases. Ovarian SLCTs without DICER1 hotspot mutations have been reported to exhibit elderly onset and no androgenic manifestations. We present the first case of a primary mesenteric SLCT without DICER1 hotspot mutation.

Case Presentation: An 84-year-old woman presented with a 75-mm mesenteric solid tumor. She presented no androgenic or estrogenic manifestations. She underwent ileocecal resection. Histologically, her mesenteric tumor showed histopathological features that resembled moderately differentiated SLCT. Moreover, DICER1 hotspot mutation was not detected.

Conclusions: We described the first case of heterotopic primary mesenteric SLCT without DICER1 hotspot mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13000-019-0805-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444432PMC
April 2019

Immunohistochemical analysis of the epithelial to mesenchymal transition in uterine carcinosarcoma.

Int J Gynecol Cancer 2019 Feb 13;29(2):277-281. Epub 2019 Jan 13.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Japan

Objective: Uterine carcinosarcoma (UCS) is a highly aggressive neoplasm that is composed of an intricate admixture of carcinomatous and sarcomatous elements. The relationship between UCS and the epithelial to mesenchymal transition (EMT) has been reported. In this study, we examined how expression of E-cadherin was associated with the expression of EMT-related proteins in UCS.

Methods: UCS samples were histologically divided into three components: carcinomatous, transitional, and sarcomatous regions. Next, we examined the expression of E-cadherin and EMT-related proteins, including SNAI2, ZEB1, and TWIST1, in each component of the UCS using immunohistochemistry. The expression score was determined by combining the staining intensity and staining area of the target cells.

Results: The expression score of E-cadherin was significantly lower in transitional and sarcomatous components than in the carcinomatous component. In addition, a significant difference in the low expression score of E-cadherin between transitional and sarcomatous components (transitional > sarcomatous components) was found. There were significant differences between the expression scores of ZEB1 in the three components (sarcomatous > transitional > carcinomatous components). However, no difference in the expression of TWIST1 between the components was found. Conversely, the expression level of SNAI2 was higher in sarcomatous or transitional components than in the carcinomatous component. However, a significant difference between the transitional and sarcomatous components was not detected.

Conclusion: These results suggest that the EMT plays an essential role in the pathogenesis of UCS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/ijgc-2018-000038DOI Listing
February 2019

Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma.

Pancreas 2019 01;48(1):36-42

From the Departments of Molecular Diagnostic Pathology and.

Objectives: The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT).

Methods: Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component.

Results: The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression.

Conclusions: Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296839PMC
January 2019

Analysis of the expression of cancer-associated fibroblast- and EMT-related proteins in submucosal invasive colorectal cancer.

J Cancer 2018 23;9(15):2702-2712. Epub 2018 Jun 23.

Division of Gastroenterology, Department of Internal Medicine, 19-1, Morioka 020-8505, Japan.

Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) play important roles in the progression and metastasis of CRC. Although prediction of lymph node metastasis in submucosal invasive colorectal cancer (SiCRC) is important, the relationships of CAF and EMT with lymph node metastasis of SiCRC have not yet been examined. Here, we aimed to analyze the expression patterns of CAF- and EMT-related proteins in SiCRC. The expression of CAF-related markers, including α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, and adipocyte enhancer-binding protein 1, and EMT-related proteins [zinc finger protein SNAI2 (ZEB1) and twist-related protein 1 (TWIST1) in SiCRC with (n = 29) or without (n = 80) lymph node metastasis was examined by immunohistochemistry. We examined the expression patterns of biomarkers using hierarchical cluster analysis. Consequently, four subgroups were established based on the expression patterns of CAF- and EMT-related markers, and the associations of these subgroups with clinicopathological variables. : In multivariate analysis, subgroup 2, which was characterized by high expression of all markers, was correlated with lymph node metastasis ( < 0.01). Next, we examined the associations of individual biomarkers with lymph node metastasis. Multivariate analysis showed that moderately differentiated adenocarcinoma was significantly associated with lymph node metastasis ( < 0.05). : Our findings showed that expression patterns of CAF markers and EMT-related proteins may allow for stratification of patients into risk categories for lymph node metastasis in SiCRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.25646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072811PMC
June 2018

Protein expression patterns in cancer-associated fibroblasts and cells undergoing the epithelial-mesenchymal transition in ovarian cancers.

Oncotarget 2018 Jun 8;9(44):27514-27524. Epub 2018 Jun 8.

Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.

Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) contribute to invasive and metastatic abilities of ovarian cancer (OC) cells. In the present study, we attempted to identify the role of CAF- and EMT-related proteins in OCs, including serous carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma using an immunohistochemical approach. The following CAF-related markers were used: CD10, podoplanin, fibroblast activating protein (FAP), platelet derived growth factor receptor (PDGFRα), PDGFRβ, S100A4 and α-smooth muscle actin (α-SMA). In addition, the following EMT-related markers were investigated: Slug, TWIST1 and ZEB1We performed hierarchical cluster analysis to group the samples according to their scoring. Subgroup 1 was characterized by high expression of CD10, podoplanin, α-SMA, Slug and ZEB1, whereas subgroup 2 was closely associated with high expression of podoplanin, PDGFRα, PDGFRβ, α-SMA, and Slug. In addition, marked expression of CD10 was observed in subgroup 3. High expression of α-SMA was a distinctive feature in subgroup 4, and expression of podoplanin and α-SMA characterized subgroup 5. Each subgroup was correlated with a histological type. The fact that different histological types were associated with different subgroups suggests the presence of distinct and heterogeneous subpopulations of CAFs in OC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.25518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007939PMC
June 2018

Primary Central Nervous System Lymphoma Presenting as Growing Intracerebral Hemorrhage.

World Neurosurg 2018 Aug 23;116:155-158. Epub 2018 May 23.

Department of Pathology and Bioscience, Hirosaki Graduate School of Medicine, Hirosaki, Japan.

Background: Hemorrhage at presentation in primary central nervous system (CNS) lymphoma is rare. We encountered a case of primary CNS lymphoma presenting as a growing intracerebral hemorrhage.

Case Description: An 80-year-old man presented with mild dysarthria. Computed tomography demonstrated a round, high-density mass with surrounding vasogenic edema in the left frontal lobe. Although the patient was placed on antihypertensive therapy for suspected subacute subcortical hemorrhage, neurologic symptoms gradually worsened. Computed tomography after 2 weeks revealed that the high-density lesion and surrounding edema had increased in size compared with previous images. The patient had been transferred to our hospital 14 days after admission to another institution. Magnetic resonance imaging demonstrated a mass lesion comprising hemorrhage of different phases in the left frontal lobe. Contrast-enhanced T1-weighted imaging demonstrated a mass lesion with heterogeneous enhancement in the left frontal lobe. The patient underwent craniotomy with gross total removal of the hemorrhagic lesion. The histopathologic diagnosis was diffuse large-cell non-Hodgkin lymphoma, and immunohistochemistry showed high immunoreactivity for vascular endothelial growth factor.

Conclusion: Although exceedingly rare, primary central nervous system lymphoma can present as growing intracerebral hemorrhage due to repeated intratumoral hemorrhages. High expression of vascular endothelial growth factor and the mass effects of hemorrhage could be associated with the onset and growth of intracerebral hemorrhage. Early evaluation and meticulous observation are important to avoid progressive, life-threatening situations in such cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2018.05.107DOI Listing
August 2018