C-ERB-2 GENE AMPLIFICATION - A MOLECULAR MARKER IN RECURRENT BLADDER-TUMORS

C-erbB-2 gene amplification and protein overexpression have been impli cated as prognostic markers for patients with recurrent progressive bl adder tumors, This event has been investigated as a potential diagnost ic indicator in archival samples of transitional cell carcinoma of the bladder. Two hundred thirty-six bladder tumors from 89 patients with recurrent disease (mean follow-up, 4 years), 20 tumors from patients w ith no evidence of bladder tumor recurrence (mean follow-up, 7 years) and 10 normal bladder controls (patients with no history of transition al cell carcinoma) were studied, A differential PCR was used to provid e a semiquantitative estimate of C-erbB-2 gene amplification. Protein overexpression was assessed immunohistochemically. Sixteen of 89 patie nts with recurrent disease had evidence of C-erbB-2 gene amplification , No C-erbB-2 gene amplification was seen in the nonrecurrent tumors o r normal bladder controls. Of the 89 patients with recurrent bladder t umors, 43 had evidence of progressive disease, and of these, 14 patien ts exhibited C-erbB-2 gene amplification, indicating a strong associat ion with gene amplification and progressive disease (P < 0.0005), Gene amplification in these patients was seen only after disease progressi on had occurred, Protein overexpression was seen in 50% of patients wi th recurrent and 45% of patients with nonrecurrent disease, No protein overexpression was seen in normal controls, Protein overexpression co uld not be linked to disease progression. C-erbB-2 gene amplification and protein overexpression were of predictive value in multivariate an alysis for overall bladder cancer death; however stage and grade remai ned the most important independent prognostic variables. C-erbB-2 gene amplification and protein overexpression were of no value as independ ent markers for the prediction of disease recurrence or progression. I t appears from these results that the role of C-erbB-2 as a diagnostic marker may far outweigh its usefulness as a prognostic indicator.