[The clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma].
OBJECTIVE
To investigate the clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma.


METHODS
Immunohistochemical 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.


RESULTS
Among 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%.


CONCLUSIONS
There 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.
Xiang
Yi-ning
YN
Department of Pathology, Guiyang Medical College, Guiyang 550004, China.
Zhang
Wei-yuan
WY
D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019292:Skull Base Neoplasms / Q000473:pathology; D015996:Survival Rate
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm