Expression of p21WAF1/CIP1 is unrelated to p53 tumour suppressor gene status in oral squamous cell carcinomas.
The p53 tumour suppressor gene is frequently mutated in oral squamous cell carcinomas. However, the downstream mechanism of p53 during oral carcinogenesis is not fully understood. The cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21), which can be induced by wild-type p53, functions as a downstream mediator of the antiproliferative and apoptosis-inducing actions of wild-type p53. To learn more about the roles of the p53 gene and its downstream mechanism, we evaluated p53 gene mutation and immunohistochemical expression of p53 and p21 in 20 cases of oral squamous cell carcinoma. p53 gene mutations were observed in 7 cases (35%). Overexpression of p53 was found in 4 of 13 cases with wild-type p53, and in 6 of 7 cases with p53 mutations. p21 expression was detected in 15 of 20 cases (75%). The expression of p21 correlated neither with mutated p53 mutation nor with p53 protein overexpression. p21 was expressed even in carcinomas in which molecular analysis revealed a nonsense mutation. In normal oral mucosa, p21 expression was limited in the differentiating spinous cell layer. However, dysplastic or hyperplastic epithelium adjacent to the tumour demonstrated the increased expression of p21 even in the proliferating basal cell layer. These molecular and immunohistochemical data did not show any correlation with various clinico-pathologic parameters. These results suggest that p53 gene mutations and altered expression of p21 are commonly involved in oral carcinogenesis, but do not correlate with each other or with the clinico-pathologic parameters. They also suggest that p21 expression in oral squamous cell carcinomas may be induced by a p53-independent pathway.
Department of Oral Pathology, College of Dentistry, Yonsei University, Seoul, Korea.
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JI
Yook
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Kim
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53