Her-2/neu overexpression in muscle-invasive urothelial carcinoma of the bladder: Prognostic significance and comparative analysis in primary and metastatic tumors

Purpose: The prognostic significance of Her-2/neu overexpression in muscle- invasive urothelial carcinoma of the bladder is largely unknown. Accurate d etermination of Her-2/neu overexpression may have therapeutic importance. Experimental Design: Eighty consecutive cases of muscle-invasive urothelial carcinoma of the bladder treated by radical cystectomy with available foll ow-up were analyzed. In each case, one representative section was stained w ith anti-Her-2/neu. Staining was graded as 1 = faint/equivocal, 2 = moderat e, and 3 = strong and was considered positive if greater than or equal to 2 . In those cases with a metastasis, the stain was also performed in the met astatic tumor. Results were correlated with survival. Results: Twenty-two (28%) cases were considered Her-2/neu-positive in the primary tumor, and 17 of 32 (53%) wer e considered Her-2/neu-positive in the lymph node metastasis. Median surviv al for Her-2/neu-positive primary tumors was 33 months, compared with 50 mo nths for Her-2/neu-negative cases (P = 0.46). Similarly, Her-2/neu overexpr ession in the lymph node metastasis did not predict survival. Sixty metasta tic urothelial carcinomas were further studied by comparing Her-2/neu expre ssion in the primary tumor with that of the lymph node and/or distant metas tasis. Forty-five % of Her-2/neu-negative primary tumors had a Her-2/neu-po sitive lymph node metastasis, whereas only one case (8%) of Her-2/neu-posit ive primary tumors was Her-2/neu-negative in the lymph node metastasis (P = 0.009). Similarly, 67% of Her-2/neu-negative primary tumors had a Her-2/ne u-positive distant metastasis, whereas no Her-2/neu-positive primary tumor was negative in the metastasis (P = 0.429). Conclusions: Her-2/neu overexpression in primary or metastatic tumor did no t predict survival in this cohort of muscle-invasive tumors. Overexpression in the primary tumors consistently predicts overexpression in a distant or regional metastasis. However, some Her-2/neu-negative primary tumors may s how overexpression in their corresponding metastasis. Her-2/neu analysis in a metastasis may be necessary to accurately determine Her-2/neu status in metastatic bladder urothelial carcinoma.