Alterations of the p16-pRb Pathway and the Chromosome Locus 9p21-22 in Non-Small-Cell Lung Carcinomas Relationship with p53 and MDM2 Protein Expression

摘要: The p16-pRb and p53-MDM2 pathways represent vital cell cycle checkpoints. Recent studies provide evidence that these are directly linked via MDM2-pRb interaction p53 suppression of the RB1 gene. In present study we investigated alterations this G1 phase protein network using immunohistochemical molecular methods in a series 68 non-small-cell lung carcinomas (NSCLCs) correlated findings with clinicopathological features prognosis patients. Aberrant expression (Ab) p16 pRb was observed 33 (49%) 27 (40%) carcinomas, respectively. Analysis region encodes for by deletion mapping, polymerase chain reaction (PCR)-based methylation assay PCR single-strand conformation polymorphism (SSCP) analysis revealed deletions transcriptional silencing might main mechanisms CDKN2/p16ink4a inactivation NSCLCs. results mapping also suggest other tumor suppressor genes may reside at 9p21-22 region, which CDKN2/MTS1/p16ink4a, p14ARF, MTS2/p15ink4b. addition, microsatellite instability frequency 16% chromosome area. Overexpression (P) MDM2 proteins found 39 (58%) 47 (70%) cases, A highly significant association between overexpression mutations (P = 0.006). Statistical patterns biologically relevant molecules (p16/pRb, p53/MDM2, MDM2/pRb, p53/pRb) showed coincident 0.04) abnormal elevated levels 0.013) 0.01), We deregulated act synergistically. An important finding multiple impairments (three four affected) p16/pRb/p53/MDM2 occurred large proportion (43%) carcinomas. This addition to absence correlation clinical stage tumors suggests hits be relatively early event development subset relationship factors examined study, features, survival patients did not reveal any correlations exception smoking, associated (loss heterozygosity instability) locus immunophenotypes p53(P)/MDM2(P) p16(Ab)/pRb(Ab)/p53(P)/MDM2(P) 0.03), NSCLCs, simultaneous deregulation members one way initiating oncogenic procedure whereas NSCLC subgroups alternative play role.