Alteredp16INK4and RB1 Expressions Are Associated with Poor Prognosis in Patients with Nonsmall Cell Lung Cancer

Abstract

p16INK4 and RB1 are two potent cell cycle regulators to control the G1/S transition by interacting with CDK4/6, E2F, and D-type cyclins, respectively. Depending on the tumour type, genetic alterations resulting in the functional inactivation have frequently been reported in both genes. By contrast, much less is known regarding the overexpression of these proteins in the tumor cells. In this study, expressions of p16INK4 RB1, and CDKN2A copy number variances (CNV) in the tumor cells were assessed by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 73 nonsmall cell lung cancer (NSCLC) with known 5-year survivals. The histologic type (P = 0.01), p16INK4 (P = 0.004), and RB1 (P < 0.001) were predictive of survivals. The CDKN2A CNV (P < 0.05) was also significant when compared to those cases without CNV. Therefore, among the molecular genetic prognostic factors, expressions of RB1 and p16INK4 in the tumor cells were the most strongly predictive of adverse outcomes in stage I and II nonsquamous NSCLC.

Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin‐remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D

“…Mutation of RB1 and copy gain of TERT are reported herein for the first time as independent predictors of poor prognosis in patients with LNETs. A correlation between alterations of these genes and poor prognosis has been observed for RB1 in non-small-cell lung cancers [37] and anaplastic astrocytoma [38], and increased mRNA expression of TERT was previously reported as a poor prognostic marker in breast [39] and lung [40] cancers. We report for the first time that mutations affecting KMT2D in SCLC patients correlate with longer survival, as previously observed for pancreatic adenocarcinoma [41].…”

Role of Human Papillomavirus and p16 Staining in a Patient With Head and Neck Cancer Presenting With a Synchronous Lung Nodule: A Case Report and Review of the Literature

“…A meta-analysis of cigarette smoking and p16 gene promoter hypermethylation in non-small-cell lung carcinoma (NSCLC) showed that the frequency of p16 hypermethylation and loss of protein expression was higher in patients with NSCLC and smoking habits than in nonsmoking patients with NSCLC. 16 Thus, the contextual, or perhaps more importantly, the mechanistic causes of overexpres-sion of p16 are key in assigning it a prognostic value. 14 Yanagawa et al 15 recently concluded that there is no association between HPV and NSCLC, and that p16 protein expression should not be used as an independent or surrogate marker for the presence of HPV in lung nodules.…”

Robust foreground detection in somatic copy number data

“…those potentially informing prognosis and/or treatment either as standard of care or in the context of a clinical trial. We defined actionable events using annotations from Memorial Sloan Kettering Cancer Center's OncoKB database (26) with the addition of some genes known to be prognostic in a particular cancer type (CDKN2A deletion (27) and MDM2 amplification (28) in non-small cell lung cancer, PTEN deletion (29) in prostate adenocarcinoma). We computed precision and recall using the SNP6 annotation as the gold standard for both WES and TP analyses.…”