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.
Kuropkat
Christiane
C
Department of Otolaryngology, Head and Neck Surgery, Philipps University, Deutschhausstr. 3, 35037, Marburg, Germany. kuropkat@hno-marburg.de
Venkatesan
T K
TK
Caldarelli
D D
DD
Panje
W R
WR
Hutchinson
J
J
Preisler
H D
HD
Coon
J S
JS
Werner
J A
JA
D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D009959:Oropharyngeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D006657:Histones; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C493956:CDKN1A protein, human