Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers

Abstract

The predictive role in terms of pathological response and prognostic role of biomarkers such as GST-\u3c0, p53, bcl-2 and bax expression, immuno- histochemically detected, and of the S-phase cell fraction, autoradiographically determined as thymidine labeling index (TLI), were investigated within a prospective randomized phase III clinical trial on squamous-cell carcinoma of the oral cavity, including surgery or primary chemotherapy (PCT), which foresaw the prospective determination of biological markers. Pathological response was defined as the achievement after PCT of a pathological complete remission or the presence of microresidual disease. The study was performed on tumors obtained from a series of 100 previously untreated patients with resectable T2-4N0-2M0 carcinoma. All biomarkers were unrelated, except for an inverse relation between TLI and GST-\u3c0 and a direct relation between bcl-2 and bax expression. In patients treated with surgery alone, 3-year disease-free survival (DFS) appeared to be weakly, but not significantly, related only to GST-\u3c0 and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST-\u3c0 and bax expression were indicative of pathological response but lost relevance as predictors of DFS, whereas absence of bcl-2 was associated with high probability of 3-year DFS in the overall series as well as in non-responding patients. Within this latter sub-set, all patients with bcl-2-positive tumors relapsed within I year of surgery, whereas a 60% probability of 3-year DFS was observed for patients with bcl-2-negative tumors (p - 0.02). This interim analysis appears to indicate that some biofunctional markers can provide information on pathological response to PCT and could help in understanding treatment efficacy at a cellular level