Bcl-x(L) and Bcl-2 expression in squamous cell carcinoma of the head and neck

BACKGROUND. Inhibition of apoptosis, or programmed cell death, may be criti cal both in the development of cancer and in determining response to therap y. The authors examined the expression of two related apoptotic inhibitors, Bcl-2 and Bcl-x(L), in pretreatment biopsies from a series of 42 patients with, squamous cell carcinoma of the head and neck. The observed pattern of apoptotic inhibitor expression was compared with that of the p53 gene prod uct, another factor implicated in carcinogenesis and therapeutic responsive ness. METHODS. Formalin fixed, paraffin embedded tumor biopsies from 42 patients with locally advanced squamous cell, carcinoma of the head and neck were an alyzed by immunohistochemistry using antibodies specific far Bcl-x(L), Bcl- 2, and p53. Measures of clinical outcome, including disease specific surviv al and overall survival, were compared among the groups. RESULTS. The majority of the tumors demonstrated enhanced expression of eit her Bcl-2 or Bcl-x(L) compared with surrounding normal epithelium. Fifty-tw o percent of the tumors had up-regulated Bcl-x(L), and 17% had up-regulated Bcl-2. There was no overlap between these groups. Expression of Bcl-2, but not Bcl-x(L), was correlated with improved disease specific survival. Immu nohistochemically detectable p53 expression (48% of tumors) was not found t o correlate with expression of either Bcl-x(L) or Bcl-2 and, in this series , was not a predictor of clinical outcome. CONCLUSIONS. These results suggest that disruption of apoptotic control pat hways is an important event in the evolution of squamous cell carcinoma of the head and neck. A common mechanism for this disruption involves overexpr ession of Bcl-x(L). Patients whose tumors demonstrate Bcl-2 positivity, eve n with locoregionally advanced disease, appear to have a high likelihood of cure with aggressive combined modality therapy and may be treated successf ully with less toxic therapy. Cancer 1999;85:164-70. (C) 1999 American Canc er Society.