Tissue microarray based analysis of prognostic markers in invasive bladder cancer: much effort to no avail?

To evaluate altered protein expression with tissue microarray methodology for 15 different markers with potential prognostic significance in invasive bladder cancer.

Invasive tumor was sampled with the tissue-arraying instrument in 133 consecutive patients who underwent radical cystectomy, and at least 3, 0.6-mm tissue cores were obtained. With immunohistochemistry, the expressions of TP53, RB1, CDKN1A (p21), MKI67 (Ki67), PTGS2 (Cox-2), CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), AKT, PTEN, RHOA, RHOC, STAT1, VEGFC, EGFR, and ERBB2 (HER2) were quantified, and correlations were made with tumor grade, pathologic stage, lymph node status, and disease-specific survival.

Decreased immunohistochemical expression of CTNNA1 and of PTEN correlated with higher pathologic tumor stages (P = 0.01 and P = 0.01, respectively), whereas increased AKT1 and ERBB2 correlated with lower pathologic tumor stages (P = 0.01 and P = 0.03, respectively). Increased RHOA expression was more common in grade 3 than in grade 2 tumors (P = 0.016). There were no other correlations among the 15 factors studied and pathologic stage, lymph node status, or tumor grade. No association was found between bladder cancer death and altered marker status for any of the markers studied.

Currently, there are reasons to have a skeptical attitude toward the value of tissue microarray based immunohistochemistry as a method for evaluating prognostic markers in invasive bladder cancer. In this study, 15 antibodies were tested but were found to be of little clinical value. Whether this negative finding is related to the group of patients or factors studied, or the methodology is unclear.