PubMed · 8416652
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M H Lev, F S Chew. 1993. Transitional cell carcinoma.. https://doi.org/10.2214/ajr.160.1.8416652
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The uroplakins are widely regarded as urothelium-specific markers of terminal urothelial cytodifferentiation. This study investigated the expression of the four uroplakin genes, UPIa, UPIb, UPII and UPIII, in a wide range of normal human tissues to determine tissue specificity and in advanced transitional cell carcinoma (TCC) to examine gene expression in primary and metastatic disease. In the urinary tract, all four uroplakins were expressed by urothelium and UPIII was also expressed by prostatic glandular epithelium. UPIa and UPII appeared to be urothelium-specific, but UPIb was detected in several non-urothelial tissues, including the respiratory tract, where it was associated with squamous metaplasia of tracheal and bronchial epithelia. The ten cases of primary TCC and corresponding lymph node metastases demonstrated that each uroplakin gene could be expressed at the mRNA level. No single uroplakin gene was expressed in all primary tumours or metastases, but 80% of the primary tumours and 70% of the lymph node metastases expressed at least one uroplakin gene. UPIII mRNA was often expressed in the absence of UPIII protein. These results confirm that in human tissues the expression of UPIa and UPII genes is highly specific to urothelium and suggest that the tight differentiation-restricted expression of uroplakin genes in normal urothelium is lost following malignant transformation.
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PURPOSE: Connexin 26 is the major gap junction protein in urothelial and mammary epithelial cells, and a putative tumor suppressor gene. We evaluated connexin 26 expression in normal urothelium and in bladder cancer. MATERIALS AND METHODS: A total of 40 formalin fixed, paraffin embedded bladder tumors and 5 normal urothelial specimens were analyzed by immunohistochemistry. Two observers visually scored connexin 26 expression in these specimens. RESULTS: Normal urothelium expressed connexin 26 in a punctate staining pattern with limited expression in the basal layer. Decreased connexin 26 expression was observed in 28 of 40 tumors (70%). Connexin 26 was diffusely expressed in 5 of 18 low grade, noninvasive tumors (28%), whereas loss of expression was observed in heterogeneous (30% to 70% positive staining) or extensive (less than 30% positive staining) fashion in 8 (44%) and 5 (28%), respectively. Seven of 22 high grade or invasive tumors (32%) showed diffuse connexin 26 expression, whereas expression was decreased in a heterogeneous or extensive pattern in 9 (41%) and 6 (27%), respectively. Intracytoplasmic localization of connexin 26 was also observed. CONCLUSIONS: Expression of connexin 26 is altered in bladder cancer. These aberrant patterns of connexin 26 expression may contribute to the malignant phenotype of this disease.