Differential expression of WNT5A long and short isoforms in non-muscle-invasive bladder urothelial carcinoma.

Wnt ligands belong to a family of secreted glycoproteins in which binding to a range of receptors/co-receptors activates several intracellular pathways. WNT5A, a member of the Wnt family, is classified as a non-canonical Wnt whose activation triggers planar cell polarity (PCP) and Ca+2 downstream pathways. Aberrant expression of WNT5A has been shown to play both protective and harmful roles in an array of conditions, such as inflammatory disease and cancer. In the present study, using histological, immunohistochemical, and molecular methods, we investigated the expression of two isoforms of WNT5A, WNT5A-Short (WNT5A-S) and WNT5A-Long (WNT5A-L) in bladder urothelial carcinoma (UC). Three UC cell lines (RT4, J82, and T24), as well as a normal urothelial cell line, and formalin-fixed, paraffin-embedded (FFPE) transurethral resection (TUR) tissue samples from 17 patients diagnosed with UC were included in the study. WNT5A-L was the predominantly expressed isoform in urothelial cells, although WNT5A-S was also detectable. Further, although no statistically significant difference was found between the percentage of WNT5A-S transcripts in low-grade versus high-grade tumors, we did find a difference between the percentage of WNT5A-S transcripts found in non-invasion versus invasion of the lamina propria, subgroups of non-muscle-invasive tumors. In conclusion, both WNT5A-S and WNT5A-L isoforms are expressed in UC, and the percentage of their expression levels suggests that a higher proportion of WNT5A-S transcription may be associated with lamina propria invasion, a process preceding muscle invasion.

Coccygeal Polypoid Eccrine Nevus Presenting as a Skin Tag: Case Report and Review of the Literature.

Coccygeal polypoid eccrine nevi (CPEN) are rare, benign, cutaneous polypoid lesions localized to the coccyx region that are characterized by areas of hyperplastic eccrine ducts without hyperhidrosis. We present the case of an asymptomatic 16-month-old female with a congenital lesion in the lower sacral area and review the literature and the differential diagnosis for CPEN.

Fine Needle Aspiration of Thyroid Nodules Using the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience in a Rural Setting.

Background. Fine needle aspiration (FNA) remains the first-line diagnostic in management of thyroid nodules and reduces unnecessary surgeries. However, it is still challenging since cytological results are not always straightforward. This study aimed to examine the results of thyroid FNA using the Bethesda system for reporting thyroid cytopathology (TBSRTC) to establish the level of accuracy of FNA procedures in a rural practice setting. Method. A retrospective chart review was conducted on existing thyroid FNA performed in a referral endocrine center between December 2011 and November 2015. Results. A total of 159 patients (18-88 years old) and 236 nodule aspirations were performed and submitted for evaluation. 79% were benign, 3% atypia/follicular lesion of unknown significance (AUS/FLUS), 5% follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 4% suspicious for malignancy (one case was indeed an atypical parathyroid neoplasm by surgical pathology), 2% malignant, and 7% nondiagnostic. Two cases also had advanced molecular analysis on FNA specimens before thyroidectomy. Conclusion. The diagnostic yield of FNA cytology from our practice in a rural setting suggests that accuracy and specificity are comparable to results from larger centers.

Wnt5a / planar cell polarity signaling pathway in urothelial carcinoma, a potential prognostic biomarker.

Bladder cancer is the fourth most common cancer in men and the most common malignancy of the urinary tract. Bladder cancers detected at an early stage have a very high five-year survival rate, but when detected after local metastasis the rate is only about 50%. Our group recently reported a positive correlation between the expression of Wnt5a, a member of the Wnt proteins family, and histopathological grade and stage of urothelial carcinoma (UC). The objective of this study was to analyze UC cases reported in Athens, Ohio and investigate the major components of Wnt5a / planar cell polarity (PCP) signaling pathway in UC human tissue samples and UC cell lines.Formalin fixed and paraffin embedded transurethral resection tissues were immunostained for Wnt5a, Ror-2, CTHRC1 and E-cadherin. In addition, in vitro studies using UC cell lines were investigated for Wnt5a/PCP signaling and epithelial mesenchymal transition (EMT) gene expression. The IHC results showed a correlation between the expression of Wnt5a, Ror2 and CTHRC1 with high histological grade of the tumor, while E-cadherin showed an opposite trend of expression. Real time RT-PCR results showed that RNA expression of the Wnt5a/ PCP pathway genes vary in low and high grade UC cell lines and that the high grade cell lines exhibited signs of EMT.These findings support that Wnt5a-Ror2 signaling plays a role in UC, support the potential use of Wnt5a as a prognostic marker and provide evidence that Wnt5a signaling may be used as an effective molecular target for novel therapeutic tools.

Correlation of Wnt5a expression with histopathological grade/stage in urothelial carcinoma of the bladder.

BACKGROUND: Bladder cancer, including urothelial carcinoma (UC), is the most common malignancy of the urinary tract and the fourth most frequent cancer overall in men. Wnt5a, a member of the Wnt family of proteins, has been shown to have contradictory roles in the pathogenesis of many cancers, acting either as tumor suppressor or tumor promoter. The objective of this study was to investigate the expression and role of Wnt5a in the pathogenesis of UC and suggest possible clinical applications for diagnosis, prognosis and treatment. METHODS: We characterized the expression of Wnt5a in 33 human UC samples using immunohistochemistry. The samples were obtained via transurethral resection, immediately fixed in formalin and then embedded in paraffin. The correlation between Wnt5a immunoreactivity, histological grade, and pathological stage of the tumor was analyzed. The expression of Wnt5a mRNA as well as the effect of Wnt5a on cell migration was also evaluated in two UC cell lines, T24 and J82, and a normal urothelial cell line. RESULTS: Our immunohistochemical results revealed that Wnt5a staining intensity correlated positively with the histological grade and pathological stage of the UC. Wnt5a mRNA expression differed widely in the three urothelial cell lines, with high levels in one carcinoma cell line and low levels in the other cell line in comparison to the normal urothelial cell line. Migration increased in both UC cell lines in response to Wnt5a treatment. CONCLUSIONS: Our results show that the Wnt5a pathway may play a role in the pathogenesis of UC and suggest that Wnt5a may serve as an additional, complementary diagnostic/prognostic marker for UC. VIRTUAL SLIDE: http://www.diagnosticpathology.diagnomx.eu/vs/1952312091979566.