Differential diagnosis of bladder versus colorectal adenocarcinoma: keratin 7 and GATA3 positivity in nuclear ß-catenin-negative glandular tumours defines adenocarcinoma of the bladder.

AIMS: This study evaluates immunohistochemical markers for the differential diagnosis of primary bladder adenocarcinoma (BAC) from secondarily involving colorectal adenocarcinoma (CAC). Additional staining of putative precursor lesions (cystitis cystica et glandularis (CC) and intestinal metaplasia (IM)) supports insights into metaplastic cell development and aberrant differentiation in tumours. METHODS: Tissue microarray sections of formalin-fixed, paraffin-embedded tissues from clinically verified 11 BAC, 11 CAC, 18 invasive urothelial carcinomas (UCs), 22 normal urothelium samples, 25 CC and 15 IM were stained for keratin 7, 5/6, 5/14 and 20, ß-catenin, e-cadherin, cadherin 17, cdx2, uroplakin II and III, CD10, androgen receptor (AR), S100P, MUC2, MUC5AC and GATA3 expression. Data were analysed using Kruskal-Wallis/Dunn's multiple comparison test and Fisher's exact test. RESULTS: Significant difference (p<0.05) between all three tumour groups was observed for keratin 7 only. Further significant difference between BAC and CAC was found for GATA3 and nuclear ß-catenin staining. BAC-positive/CAC-negative markers without significance were: p63, keratin 5/6, 5/14, uroplakins II/III and AR. CC showed a urothelial phenotype (p63+, GATA3+, S100P+, uroplakin+ in single cells) with initial signs of intestinal differentiation (single cells cdx2+ or cadherin 17+). IM displayed a full intestinal phenotype (p63-, all urothelial markers-, cdx2/MUC2/MUC5AC+, cadherin17+). CONCLUSIONS: Differential diagnosis of BAC and CAC remains difficult, but positive staining for keratin 7 in nuclear ß-catenin-negative tumours argues for BAC. Additional markers like GATA3 and p63 may be added, as positivity in some cases may be helpful. However, for reliable histological diagnosis, knowledge of comprehensive clinical data is still essential.

p40 in Conjunction With CK20 and E-Cadherin Distinguishes Primary Adnexal Neoplasms of the Skin.

Although basal cell carcinomas (BCC) show typical histomorphologic features, they sometimes remain difficult in distinction from benign adnexal skin tumors of follicular origin like trichoepithelioma (TE) or trichoblastoma (TB). Consequently, an immunohistochemical marker panel separating described entities would be helpful in clinical routine. Thus, we stained 22 skin lesions (BCC, TE, and TB) against ß-catenin, CK20, E-cadherin, p40, and p63. The staining pattern was described and quantified using an immunohistochemical score. Although p40 and p63 revealed a strong staining intensity of all skin lesions without distinction between BCC and benign lesions (P=1.000), established Merkel cell marker CK20 illustrated a loss of staining in BCC compared with TE and TB (P=0.007). In contrast, BCC exhibited an increased expression of E-cadherin in relation to TE and TB (P=0.009). Single application of CK20 or E-cadherin could predict diagnosis of BCC in 81.8% or 72.7%, respectively. Combining consecutive staining of E-cadherin and CK20 could even enhance specificity toward diagnosis of TE or TB. Hence, findings of our study imply that sequential staining of CK20 and E-cadherin prevents false-positive classification of BCC. Furthermore, our study demonstrated that p40 exhibits the same staining pattern in BCC, TE, and TB. Therefore, p40 might replace p63 equivalently establishing diagnosis of primary adnexal neoplasms of the skin in the form of BCC as well as benign adnexal tumors. As a result, the depicted immunohistochemical marker panel may be applied for adnexal skin neoplasms as a diagnostic adjunct especially in surgically challenging body regions.

Identification of prostaglandin receptors in human ureters.

BACKGROUND: Prostaglandins play an important role in ureteral obstruction, but the detailed expression profiles of the prostaglandin receptors (PTGER1, PTGER2, PTGER3, PTGER4, PTGFR) remain unknown in the different parts of the human ureter. METHODS: The expression pattern of PTGER1, PTGER2, PTGER3, PTGER4 and PTGFR was determined in human distal, mid and proximal ureter and renal pelvis samples using immunohistochemistry (protein levels) and quantitative real-time PCR (mRNA). RESULTS: PTGER1 was highly expressed in most samples irrespective of the ureteral localization; however, urothelial cells had higher levels of PTGER1 than smooth muscle cells. PTGFR was also moderately to strongly expressed in urothelial and smooth muscle cells. In comparison, PTGER2-4 expression was mostly unexpressed or weakly expressed in urothelial and smooth cells in all regions. CONCLUSIONS: Our data indicate high levels of PTGER1 in ureters.