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The epithelial and mesenchymal features of colorectal adenocarcinoma (CRAC) cell lines were compared in two-dimensional (2D) and three-dimensional (3D) cultures. In 2D cultures, the three CRAC cell lines exhibited epithelial characteristics with high E-cadherin and low vimentin levels, whereas two exhibited mesenchymal traits with opposite expression patterns. In 3D cultures using low-attachment plates, mesenchymal cells from 2D cultures showed reduced vimentin mRNA levels. Morphologically, the five CRAC cell lines appeared similarly shaped in 2D culture but formed different structures in 3D culture. Epithelial DLD-1 and mesenchymal COLO-320 cells produced large granular spheres, whereas epithelial HCT-15 cells formed small solid spheres. Tubular structures were observed in epithelial CACO-2 and mesenchymal SW480 spheres. Desmosome-like structures developed in epithelial CRAC cells, whereas entosis was observed in CACO-2, HCT-15, and SW480 cells. The Ki-67-positive proliferating cell count varied in 2D and 3D cultures of epithelial cells but remained high and unchanged in mesenchymal cells. These findings suggest that while CRAC cells display distinct epithelial and mesenchymal properties in 2D cultures, they form diverse 3D structures, irrespective of these traits. [ABSTRACT FROM AUTHOR]

Appropriate biomarkers are required to predict the clinical outcome of triple‐negative breast cancer (TNBC). In this study, we focused on the clinical importance of two representative tumor‐associated proteins, Bcl‐2 and p53. Bcl‐2 expression is usually related to estrogen receptor expression and a favorable outcome in breast cancer. TNBC has been reported to show a high frequency of p53 positivity suggesting TP53 mutations. The expressions of Bcl‐2 and p53 were immunohistochemically examined in TNBC involving two age groups of postmenopausal women (≥75 y/o, n = 75; 55–64 y/o, n = 47), who underwent surgery without neoadjuvant therapy. We examined their associations with each other, or with clinicopathological factors including the outcome. Bcl‐2 expression was inversely correlated with androgen receptor, apocrine morphology, and p53 expressions, and was an independent predictor of a poor outcome in total or in younger women. p53 positivity was associated with a more favorable outcome than p53 negativity in the younger group. In combined analyzes, none of the twenty Bcl‐2‐negative/p53‐positive cases in the younger group exhibited recurrence, resulting in the independent favorable predictive value of Bcl‐2‐negative/p53‐positive. The anti‐apoptotic nature of Bcl‐2 may be apparent in TNBC. The excellent outcome of Bcl‐2‐negative/p53‐positive cases in the younger group warrants further combined investigation of Bcl‐2/p53 in TNBC. [ABSTRACT FROM AUTHOR]

Papillary adenocarcinoma is defined as carcinoma with a well‐defined papillary or villous structure. Despite sharing clinicopathological and morphological features with tubular adenocarcinomas, papillary adenocarcinomas frequently show microsatellite instability. The present study aimed to clarify the clinicopathological features, molecular classification, and programmed death‐ligand 1 (PD‐L1) expression characteristics of papillary adenocarcinoma, especially tumors with microsatellite instability. We examined the microsatellite status and expression of mucin core proteins and PD‐L1 as well as the clinicopathological features in 40 gastric papillary adenocarcinomas. Surrogate immunohistochemical analysis of p53 and mismatch repair proteins along with Epstein‐Barr virus‐encoded RNA in situ hybridization were performed for molecular classification. Female predominance and frequent microsatellite instability were observed in papillary adenocarcinoma in comparison with tubular adenocarcinoma. The presence of microsatellite instability in papillary adenocarcinoma was significantly correlated with older age, tumor‐infiltrating lymphocytes, and Crohn's‐like lymphoid reactions. Surrogate examination demonstrated that the genomically stable type (17 cases, 42.5%) was the most common, followed by the microsatellite‐unstable type (14 cases, 35%). Among the seven cases showing PD‐L1‐positive expression in tumor cells, four involved carcinomas with microsatellite instability. These results reveal the clinicopathological and molecular characteristics of gastric papillary adenocarcinoma. [ABSTRACT FROM AUTHOR]

Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi‐thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 μm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 μm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals. [ABSTRACT FROM AUTHOR]

Objective: Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is often challenging because of the small sample size or well‐differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer should be improved. Hence, we aimed to clarify the utility of cytological scoring to distinguish malignant from benign lesions for cytological diagnosis of pancreatic EUS‐FNA specimens. Methods: Seven reviewers, including four cytotechnologists and three medical doctors, evaluated 20 morphological indices in pancreatic specimens obtained by EUS‐FNA (malignant, n = 111; benign, n = 31). Statistical analyses were performed using Fisher's exact test, logistic regression analysis, the area under the receiver operating characteristic curve, and Youden index. Results: Among the 20 indices, there was a high incidence rate (>40%) of the following 13 indices in malignant cases: irregular structure, hyperchromatic nucleus, irregular cell polarity, unclear cell boundaries, nuclear membrane thickening, anisonucleosis, overlapping, irregular nuclei, high nuclear‐cytoplasmic ratio, binding decline, the simultaneous appearance of malignant and benign cells, enlarged nucleoli, and background necrosis. When we diagnosed pancreatic specimens using these 13 cytological indices, the cut‐off value of 8/9 showed the highest Youden index (0.950) as well as high sensitivity and specificity in distinguishing malignant from benign specimens (98% and 97%, respectively). Conclusion: Thirteen cytological indices showed high sensitivity and specificity in differentiating malignant and benign lesions using pancreatic EUS‐FNA samples. All 13 indices were important for diagnosing malignancy in the pancreatic cytology smear of EUS‐FNA. Further validation studies are required. [ABSTRACT FROM AUTHOR]