Spontaneous apoptosis in laryngeal squamous cell carcinoma is independent of bcl‐2 and bax protein expression

BACKGROUND bcl‐2 and bax genes are known to be involved in the control of apoptotic cell death, an important mechanism of growth regulation that influences the biologic behavior of tumors. The aim of the current study was to investigate the relationship of bcl‐2 and bax expression to the rate of spontaneous apoptosis in laryngeal carcinomas, and to assess its relations to clinicopathologic features of tumors. METHODS Immunohistochemical analyses for bcl‐2 and bax were performed on paraffin embedded tissue sections from 134 primary laryngeal squamous cell carcinomas. To visualize apoptotic cells, the nick end labeling method was used. The proliferative activity of tumors was analyzed by determination of mitotic indices. RESULTS bcl‐2 immunoreactivity was positively correlated with tumor grade (P < 0.00001), high T category (P < 0.02), metastatic involvement of cervical lymph nodes (P < 0.003), and supraglottic or subglottic location of primary tumors (P < 0.00005). An inverse relation was found between bcl‐2 and bax expression (P < 0.004). The frequency of spontaneous apoptosis was closely associated with mitotic activity (P < 0.0004) but appeared to be unrelated to protein levels of bcl‐2 or bax as well as to bcl‐2:bax ratios. CONCLUSIONS The results of this study point to the significance of cell proliferation as a major determinant of the rate of spontaneous apoptosis in laryngeal carcinomas. The bcl‐2:bax expression ratio obviously does not affect the incidence of apoptosis, but it may be considered as a marker of disease progression and poor prognosis. Cancer 1999;85:591–9. © 1999 American Cancer Society. In this study, the rate of spontaneous apoptosis occurring in laryngeal carcinoma was closely associated with mitotic activity but appeared to be unrelated to protein expression of bcl‐2 and bax. Elevated bcl‐2 and reduced bax levels were correlated with adverse prognostic parameters.