Mechanisms associated with abnormal E‐cadherin immunoreactivity in human bladder tumors

The involvement of E‐cadherin in the progression of carcinoma is supported by a large number of studies showing an inverse relationship between E‐cadherin immunoreactivity and tumor aggressiveness. However, the mechanisms leading to decreased E‐cadherin immunoreactivity are still unclear. Comparison of Northern blotting and immunohistochemistry in a series of 49 frozen bladder tumors revealed that, in 16 of 23 tumors with abnormal staining, clear mRNA down‐regulation occurred. In the 7 cases without mRNA down‐regulation, no structural anomalies of E‐cadherin could be detected by Southern blotting, Western blotting or PCR‐SSCP. Western blotting confirmed that, in 6 of these tumors, E‐cadherin was down‐regulated at the protein level. This down‐regulation was accompanied by down‐regulation of α‐catenin and, to a lesser extent, of β‐ or γ‐catenin. However, Northern‐blot analysis indicated that expression of the 3 catenins is maintained at the mRNA level. Thus our data show that, in bladder tumors, mRNA down‐regulation accounts for about two thirds (16/23) of tumors with abnormal staining and that post‐transcriptional down‐regulation of E‐cadherin occurs in 6/23 of these tumors. Int. J. Cancer 83:591–595, 1999. © 1999 Wiley‐Liss, Inc.