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

• Published in: Auris, nasus, larynx nasus, larynx, 2002-04, Vol.29 (2), p.165-174
• Main Authors: Kuropkat, Christiane, Venkatesan, T.K, Caldarelli, D.D, Panje, W.R, Hutchinson, J, Preisler, H.D, Coon, J.S, Werner, J.A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Apoptosis; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - pathology; Cyclin D1 - analysis; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - analysis; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Histones - analysis; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Molecular regulators; Mouth Neoplasms - chemistry; Mouth Neoplasms - pathology; Neoplasm Proteins - analysis; Oral cancer; Oropharyngeal Neoplasms - chemistry; Oropharyngeal Neoplasms - pathology; Polymorphism, Single-Stranded Conformational; Prognosis; Proliferation; Proportional Hazards Models; Proto-Oncogene Proteins c-bcl-2 - analysis; Receptor, ErbB-2 - analysis; Survival Analysis; Tumor Suppressor Protein p53 - analysis; Up-Regulation
• ISSN: 0385-8146; 1879-1476
• DOI: 10.1016/S0385-8146(01)00129-8

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.