Correlation between methylation status of the p16/CDKN2 gene and the expression of p16 and Rb proteins in primary non-small cell lung cancers

Int J Cancer. 1998 Jun 19;79(3):215-20. doi: 10.1002/(sici)1097-0215(19980619)79:3<215::aid-ijc1>;2-s.


In order to clarify the frequency of p16 gene inactivation and its relationship with Rb expression, immunohistochemical analysis of p16 and Rb proteins was carried out on 82 paraffin-embedded sections of primary non-small cell lung cancers (NSCLCs). From immunohistochemical results, abnormal p16 expression was observed in 66% of NSCLCs, 80% in squamous cell carcinomas and 46% in adenocarcinomas. An inverse correlation between p16 and Rb expressions was noted. Moreover, the methylation status of the p16 gene was investigated by the methylation-specific polymerase chain reaction (MS-PCR) using 29 frozen samples of NSCLCs. MS-PCR revealed the methylation of the p16 gene in 10(34%)of 29 NSCLCs. All NSCLCs exhibiting methylation exhibited abnormal p16 expression and were positive for Rb. In NSCLCs, no difference in methylation status was observed with respect to clinico-pathological characteristics including histological subtype and tumor stage. Our results demonstrate that abnormality of p16 expression is frequent in primary NSCLCs and methylation of the promoter of the p16 gene occurs in 34% of primary NSCLCs, which might play a significant role in the inactivation of the p16 gene.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Methylation
  • Genes, p16*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Polymerase Chain Reaction / methods
  • Retinoblastoma Protein / metabolism*


  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein