Tumour stage, node stage, p53 gene status, and bcl-2 protein expression as predictors of tumour response to platin-fluorouracil chemotherapy in patients with squamous-cell carcinoma of the head and neck

Abstract

The purpose of this study was to establish the relative contribution of tumour stage, node stage, p53 gene status, p53 expression, and bcl-2 protein expression to tumour response to platin-fluorouracil chemotherapy in 141 patients with squamous-cell carcinomas of the head and neck. Tumour response was measured at the primary site after three cycles of chemotherapy. Exons 2 -10 and the coding part of exon 11 were sequenced on both strands. Bcl-2 or p53 expression was detected by immunohistochemistry. Predictor variables of objective response (reduction of at least 50% of tumour size) were tested in univariate and multivariate analyses. P53 mutations were found in 52 patients (37%). Tumour cells expressed p53 in 84 cases (59%) and bcl-2 in 25 cases (18%). T1 or T2 stage (adjusted odds ratio, 3.3; 95% confidence intervall 1.3 -8.7; P=0.01), N0 node stage (adjusted odds ratio, 2.7; 95% confidence interval 1.1 -6.4; P=0.03), p53 wild-type gene (adjusted odds ratio, 4 .0; 95% confidence interval 1.7 -9.5; P=0.002), and bcl-2 protein expression (adjusted odds ratio, 20; 95% confidence interval 2.3 -170; P=0.006), were positively associated with tumour response. P53 protein expression was not predictive of response. In conclusion, tumour stage, node stage, p53 gene status, and bcl-2 expression are independent predictors of tumour response to platin-fluorouracil in patients with squamous-cell carcinomas of the head and neck.

Molecular markers predict outcome in squamous cell carcinoma of the head and neck after concomitant cisplatin‐based chemoradiation

“…BCL-2 has been reported to be predictive for LC in more than half of all published studies. In 4 studies 17,35,36,40 the same cut off value (>5%) was used and a significant association between BCL-2 positivity and LC was observed. Using a cut off value of 30%, a significant association was also seen in 2 other studies.…”

“…Studies describing less than 25 cases, any surgical treatment, esophageal or nasopharyngeal cancer were excluded. Based on these criteria, we selected the following markers: BCL-2, 17,26,[35][36][37][38][39][40] CA9, [18][19][20]41 23 In addition, Cortactin, XPA, MDR1 and TP73 were chosen, because these genes were of interest to the authors.…”

ΔNp63α Levels Correlate with Clinical Tumor Response to Cisplatin

“…Numerous reports have failed to show conclusively that p53 is the major determinant of chemotherapeutic response in head and neck tumors. 31,33,34 Some tumors harboring p53 mutants that failed to bind ∆Np63α, also likely to harbor high levels of ∆Np63α, 26 perhaps accounting for the tighter correlation we observed between ∆Np63 levels and response to therapy. We thus suggest that p53 family members, ∆Np63 and perhaps p73 are likely to play important roles in mediating the response to a variety of agents, and together with p53 may determine the ultimate cellular apoptotic response.…”

“…An important mechanism is thought to be through DNA damage and subsequent overexpression and stabilization of p53, which then induces apoptosis or cell cycle arrest. [28][29][30][31][32][33][34][35] Our work suggests that ∆Np63α protein levels may be an important prediction of cell response to various genotoxic stresses. In particular, SCC cells are generally sensitive to platinum containing compounds and these agents have become the cornerstone of clinical treatment.…”

Antisense-mediated downregulation of anti-apoptotic proteins induces apoptosis and sensitizes head and neck squamous cell carcinoma cells to chemotherapy

“…17 Bcl-2, Bcl-X L and Survivin overexpression has been found to be associated with chemoresistance to these agents in head and neck cancers. [18][19][20] Since these anti-apoptotic proteins are overexpressed and are responsible for chemoresistance in HNSCC, we wanted to see the effect of antisense-mediated downregulation of these anti-apoptotic genes on apoptosis in HNSCCs and their effect on chemosensitization. Hence, the aim of the present study was to overcome the anti-apoptotic block and restore the apoptosis signaling pathway in HNSCC by downregulating the expression of Bcl-2, Bcl-X L and Survivin and sensitizing these cells to chemotherapy.…”