Abnormalities of molecular regulators of proliferation and apoptosis in carcinoma of the oral cavity and oropharynx

Objective: Abnormalities in genes regulating cell proliferation and death may affect disease outcome in squamous cell carcinoma (SCC) of the head and neck. Methods: Proliferative activity (Histone H3 in-situ-hybridization (HISH) labeling index (LI)) and the genes and/or gene products of Cyclin D-1, c-erbB-2, Bcl-2, p21, and p53, were investigated in 35 patients with SCC of the oral cavity and oropharynx, previously studied for p27 expression. Results: Overexpression or very low expression of Cyclin D-1 was associated with unfavorable disease outcome and shorter time-to-recurrence. High c-erbB-2 expression was significantly associated with shorter overall survival and was synergistic with low p27 expression. Bcl-2, HISH LI, p21 expression, and p53 mutation and protein analysis were not significantly predictive, but there were trends suggesting shorter disease-free/overall survival for patients with undetectable Bcl-2, high HISH, and mutant p53. Conclusions: Several cell proliferation and death regulators appeared to predict disease outcome. Limited evidence of cooperativeness among regulators was also seen.