p16INK4A in oral squamous cell carcinomas--a correlation with biological behaviors: immunohistochemical and FISH analysis.
OBJECTIVE
The p16(INK4A) gene and Rb gene are key tumor suppressor genes in a cell cycle regulatory pathway that is commonly inactivated in various cancers. The disruption of p16(INK4A) expression has been reported in several types of carcinoma but sparse in the area of oral oncology.


METHODS
The study included 66 cases who were diagnosed as oral squamous cell carcinoma. Immunohistochemical p16(INK4A) and pRb expression, fluorescence in situ hybridization analysis were performed to the resected materials.


RESULTS
p16(INK4A) protein expressions were detected in 14 cases without lymph node metastasis versus in 4 cases with metastasis (P = .04). As to histopathological grading of the effect of chemotherapy, almost all the p16(INK4A)-positive cases (9 cases out of 10) exhibited the histological feature of being rather sensitive to chemotherapy (2B and better response according to Ohboshi and Shimosato's criteria) versus 17 of 33 negative cases (P = .02). Survival curves showed that the survival rate of patients with loss of p16(INK4A) expression was significantly worse than those with amplification and normal genetic dosage of p16(INK4A) (P < .0001).


CONCLUSIONS
The expressions of p16(INK4A) were significantly correlated with biological behavior of OSCCs. These results indicate we can use p16(INK4A) as a marker of a prognostic prediction of oral cancer and it is useful for management of OSCCs.
Suzuki
Hiroyuki
H
Department of Oral and Maxillofacial Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. hrsuzuki@hama-med.ac.jp
Sugimura
Haruhiko
H
Hashimoto
Kenji
K
D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000188:drug therapy / Q000235:genetics; D016009:Chi-Square Distribution; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000235:genetics; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein