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Sry-related high-mobility-group/HMG box 10 (SOX10) as a sensitive marker for triple-negative breast cancer Aims: Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). Methods and results: We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort. Conclusion: SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.

Mucin type O-glycosylation is a posttranslational modification of membrane and secretory proteins. Transferring of N-acetylgalactosamine, the first sugar of O-glycosylation, is catalyzed by one of the 20 isoforms of polypeptide N-acetylgalactosaminyltransferases (GALNTs). In this study, Vicia villosa lectin (VVL), a lectin that recognizes O-GalNAcylated glycans, was used to detect VVL-binding glycans (VBGs) in cholangiocarcinoma (CCA). The elevation of VBGs in tumor tissues of the liver fluke associated with CCA from hamsters and patients was noted. VBGs were detected in hyperplastic/dysplastic bile ducts and CCA but not in normal biliary epithelia and hepatocytes, indicating the association of VBGs with CCA development and progression. GALNT5 was shown to be the major isoform found in human CCA cell lines with high VBG expression. Suppression of GALNT5 expression using siRNA significantly reduced VBG expression, signifying the connection of GALNT5 and VBGs observed. Knocked-down GALNT5 expression considerably inhibited proliferation, migration and invasion of CCA cells. Increased expression of GALNT5 using pcDNA3.1-GALNT5 expression vector induced invasive phenotypes in CCA cells with low GALNT5 expression. Increasing of claudin-1 and decreasing of slug and vimentin expression together with inactivation of Akt/Erk signaling were noted in GALNT5 knocked-down cells. These observations were reversed in GALNT5 over-expressing cells. GALNT5-modulated progression of CCA cells was shown to be, in part, via GALNT5-mediated autocrine/paracrine factors that stimulated activations of Akt/Erk signaling and the epithelial to mesenchymal transition process. GALNT5 and its O-GalNAcylated products may have important roles in promoting progression of CCA and could possibly be novel targets for treatment of metastatic CCA.

BACKGROUND:The aim of the International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology is to improve cytology practice. This study assessed cytologic diagnoses made with the system and its efficacy when it was applied by pathologists with different levels of experience. METHODS: In all, 1080 cases of breast fine-needle aspiration biopsy (FNAB) over a period of 16 years were reviewed and reclassified with the system. The category distribution and the diagnostic performance were compared with the original diagnoses. The concordance rates for diagnoses from pathologists with different levels of experience were also determined. RESULTS: The distribution of cytologic diagnoses made with the system was as follows: 11.7% were insufficient, 56.6% were benign, 20.1% were atypical, 6.1% were suspicious for malignancy, and 5.6% were malignant. The rates for the insufficient and atypical categories were lower than the original diagnosis rates (13.1% and 23.8%, respectively). Overall, 120 cases (11.1%) were recategorized. Among those recategorized as benign, suspicious, or malignant with follow-up data, 96.7% were correctly reclassified. A significant improvement in diagnostic performance was found with the system (P < .001). Such improvement was also seen in problematic breast lesions, including fibroepithelial lesions, papillary lesions, and low-grade carcinomas. Pathologists with intermediate experience showed a higher concordance with an expert pathologist in the diagnoses than those with short experience (κ, 0.838 vs 0.634). CONCLUSIONS:The system effectively categorized the diagnoses, and the diagnostic performance of FNAB reporting was improved. The structured reporting also enhanced the reproducibility of reporting by pathologists with intermediate experience and, to some extent, those with short experience.

Background The cytologic diagnosis of papillary lesions of the breast is challenging because of the diverse morphology, including epithelial hyperplasia, atypia, low‐grade malignancy, and neuroendocrine differentiation; also, traditional malignant features such as necrosis and myoepithelial cell loss can be lacking. Thus, the diagnostic criteria for papillary lesions may differ from those for other breast lesions. This study evaluated various cytologic parameters in a large cohort to identify useful diagnostic features. Methods Cytologic preparations of papillary lesions with histologic follow‐up were reviewed for features related to cellularity, epithelial cohesiveness, cellular and stromal architecture, cytomorphology, and background. Corresponding histologic slides were also reviewed. Results In all, 153 cases were included. Epithelial discohesion, solid and cribriform patterns, atypical nuclear features, and mitoses (P ≤ .001 to P = .017) were associated with malignancy. Cell balls, monolayer sheets, and features of cystic change (P < .001 to P = .016) were associated with benign lesions. Complex (P = .031) and slender (P = .026) papillae and neuroendocrine features (P < .001) were associated with malignancy. Hemorrhage, background, and infiltrating neutrophils (P < .001 to P = .025) were associated with malignancy; fibrotic broad papillary stromal fragments (naked papillary fronds [NPFs]; P = .043) were associated with benignity. The presence of any single parameter, including the absence of myoepithelial cells within epithelial structure, the presence of cytoplasmic granules, an increased amount of cytoplasm, and a nuclear to cytoplasmic (N/C) ratio greater than 0.7, which were identified by principal component analysis, yielded a sensitivity of 95.1% and a specificity of 100.0% in predicting malignancy. Conclusions Methodological assessment of multiple features is recommended. Myoepithelial cells, cytoplasmic granules, the amount of cytoplasm, and the N/C ratio are key features for diagnosis.

Distal cholangiocarcinoma (dCCA) is a rare type of CCA in Asia, even in Opisthorchis viverrini-prevalent Northeastern Thailand. The clinical ambiguity and imprecision of diagnosis surrounding this malignancy result in high mortality due often to advanced/metastatic disease on presentation. We aim to identify a prognostic factor that can improve the performance stratification and influence the outcome of dCCA patients after curative resection. A total of 79 patients who underwent curative-intended surgery for dCCA was enrolled. Possible risk factors for survival were analyzed with log-rank test, and independent factors with Cox regression model. dCCA patients were staged and classified according to the 8th edition the American Joint Committee on Cancer (AJCC) Staging Manual. Results were then compared with the revised classification employing the prognostic factor identified from multivariate analysis. Multivariate analysis revealed that growth pattern (p &lt; 0.01) and distant metastasis (p = 0.012) were independent factors. Growth patterns comprise intraductal (ID), periductal infiltrating (PI), mass-forming (MF), and mixed types. When dCCA patients were grouped into those having good and poor outcomes (with and without ID components, respectively). The survival outcomes significantly differed among patients with and without ID components, which was better than with the 8th AJCC staging system in our cohort. Furthermore, Chi-square test showed that patterns without ID components (PI, MF, PI + MF) correlated with lymph node and distant metastasis. Therefore, classification of dCCA patients after curative-intended surgical resection based on growth pattern provides additional beneficial information for the prediction of survival in dCCA patients.

Background: Papillary structures are frequently encountered in metastatic carcinomas from various organs and tumours of different histotypes. This study aims to investigate the predictive value of fine needle aspiration cytology (FNAC), immunohistochemistry (IHC) and the clinical parameters which can be examined in the assessment of the primary sites of metastatic carcinomas with papillary architecture.Methods: FNAC samples of metastatic carcinomas with papillary architecture were evaluated for overall cellularity, epithelial cohesion, background features, papillary architecture, cytology and IHC. The corresponding clinical information was also reviewed.Results: A total of 130 cases were included. The most common primary sites were thyroid (38.5%), lung (30.8%) and gynecological organs (22.3%); the others were pancreaticobiliary, urothelial, colorectal, and esophageal. Age (P = 0.039), biopsy site (P < 0.001) and laterality (P = 0.006) correlated with primary site. Papillary structures were confirmed on biopsy/excision of most cases (n = 85/87, 97.7%). Thyroid primaries exhibited broad papillary stalks, thin lining epithelium, fewer epithelial polymorphs, and the presence of background giant cells and histiocytes (P = 0.021-< 0.001). Lowgrade cytological features, nuclear grooves and inclusions (P < 0.001) were seen in thyroid primaries. High-grade features (P < 0.001-0.49), multinucleated tumour cells, apoptotic bodies and mitoses (P < 0.001-0.49) were more common in lung/gynecological primaries. Multivariate analysis identified nuclear/cytoplasmic ratio, chromatin character, the presence of nuclear grooves and mitosis as independent features (P = 0.001-0.024). TTF1/TGB/PAX8 panel results showed good agreement with the cytological assessment and site of primary. Conclusion:Papillary structures and cytological features are reproducible in FNAC assessment of metastases and their corresponding primary sites. Cytological features, IHC and clinical information are invaluable in determining the primary site.

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