Altered p16INK4 and Retinoblastoma Protein Status in Non-Small Cell Lung Cancer: Potential Synergistic Effect with Altered p53 Protein on Proliferative Activity

摘要: p16INK4 protein (p16) and retinoblastoma (pRB), like p53 protein, are important tumor suppressors that regulate the cell cycle. We immunohistochemically examined fresh-frozen specimens of 114 resected non-small lung cancers (NSCLCs) for loss p16 pRB expression, together with aberrant accumulation proliferative activity determined by Ki-67 index. Three pRB-positive tumors were uninterpretable status. Of remaining 111 tumors, 30 (27%) lacked 10 (9%) lost expression. No showed coincident both proteins, supporting hypothesis they function in a single pathway. 25 including 4 p16-negative Southern blot analysis, only 2 considered to have reduced gene dosage consistent possible homozygous deletion CDKN2 encoding p16, suggesting immunohistochemistry is sensitive suitable method screen alteration. Loss expression did not correlate any clinical factors or status, whereas correlated heavy smoking ( P = 0.03 Fisher's exact test 0.01 multivariate logistic regression analysis). Proliferative was considerably higher p53-positive than p53-negative < 0.001). associated further increase 0.009) but tumors. These results suggest alteration p16/pRB pathway relatively frequently involved development progression NSCLCs its effect on potentially synergistic altered protein.