Focal S100A4 protein expression is an independent predictor of development of metastatic disease in cystectomized bladder cancer patients.

Abstract

The prognosis of patients with apparently localized, operable, muscle-invasive bladder cancer depends to a large extent on the presence or absence of subclinical, microscopic distant metastases at the time of surgery. Expression of the S100A4 protein has been shown to correlate with the risk of metastasis in both animal tumour-model systems and clinical investigations in other tumour types. The purpose of the present study was to investigate the prognostic potential of S100A4 protein expression for predicting distant metastatic relapse in muscle-invasive bladder cancer. We analyzed 108 consecutive patients, treated for transitional cell bladder cancer with preoperative radiotherapy and cystectomy. Pretherapeutic biopsies of the bladder tumours were investigated for immunohistochemical expression of S100A4 protein and results, along with clinical and histopathological data, compared with the pattern of relapses over a 10+ yr follow-up period. Focal S100A4 protein expression emerged as the only significant independent predictor of distant metastatic relapse and distant metastasis-free survival in multivariate analysis. There is a potential role for this marker in denoting patients with high or low risk of distant relapse independent of clinical stage and grade.