The clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma.
- Author:
Yi-ning XIANG
1
;
Wei-yuan ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: CpG Islands; Cyclin-Dependent Kinase Inhibitor p16; metabolism; DNA Methylation; DNA, Neoplasm; genetics; Exons; genetics; Gene Deletion; Gene Expression Regulation, Neoplastic; Genes, p16; Humans; Nasopharyngeal Neoplasms; genetics; metabolism; pathology; Neoplasm Invasiveness; Neoplasm Metastasis; Skull Base Neoplasms; pathology; Survival Rate
- From: Chinese Journal of Pathology 2005;34(6):358-361
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma.
METHODSImmunohistochemical study for p16 protein was carried out in 90 cases of non-keratinizing carcinoma (NKC) of nasopharynx. P16 gene deletions and hypermethylation were also analyzed by polymerase chain reaction (PCR) and methylation-specific PCR in 23 randomly selected NKC cases.
RESULTSAmong the 90 NKC cases studied, 42 cases (46.7%) were negative for p16 protein. The non-expression rate of p16 protein also correlated with the 5-year survival rate. The non-expression rate was 60.0% in patients who died within 5 years, in contrast to 20.0% in those alive for over 5 years after diagnosis. The non-expression rate of p16 protein in cases with or without distant metastasis was 81.8% and 41.8% respectively (P < 0.05), while that in cases with or without local invasion into skull base was 41.7% and 48.5% respectively (P > 0.05). As for molecular analysis, deletion of p16 gene exon 2 was found in 10 of the 23 cases (43.4%) studied, while deletion of p16 gene exon 1 was not detected in these samples. Hypermethylation of p16 gene exon 1 was also noted in 2 of the 23 cases (8.7%). The overall mutation rate of these cases was 52.1%.
CONCLUSIONSThere is a high incidence of p16 protein non-expression, deletion of p16 gene exon 2 and hypermethylation of p16 gene exon 1 in NKC. P16 gene inactivation may thus play an important role in the pathogenesis of NKC, especially in terms of its metastatic potential.