Location of Repository

Altered p16INK4 and RB1 Expressions Are Associated with Poor Prognosis in Patients with Nonsmall Cell Lung Cancer

By Weiqiang Zhao, Cheng C. Huang, Gregory A. Otterson, Marino E. Leon, Yan Tang, Konstantin Shilo and Miguel A. Villalona


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

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3350860
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (1999). Alterations of expression of Rb, p16(INK4A) and cyclin D1 in non-small cell lung carcinoma and their clinical significance,”
    2. (2010). CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival,”
    3. (2001). CDKN2A germline splicing mutation affecting both
    4. (2008). Chromosome 9 instability and alterations of p16 gene in squamous cell carcinoma of the lung and in adjacent normal bronchi: FISH and immunohistochemical study,”
    5. (2008). Chromosome 9 instability and alterations of p16 gene in squamous cell carcinoma of the lung and inJournal of Oncology 7 adjacent normal bronchi: FISH and immunohistochemical study,”
    6. (1991). Comparative study of the expression of Rb and p53 genes in human colorectal cancers, colon carcinoma cell lines and synchronized human fibroblasts,”
    7. (1997). Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas,”
    8. (2008). DNA methylation markers and early recurrence in stage I lung cancer,”
    9. (1995). Evidence for different modes of action of cyclin-dependent kinase inhibitors:
    10. (2006). h a o ,D .F .C l a x t o n ,L .J e ffrey Medeiros et al., “Immunohistochemical analysis of CBFβ-SMMHC protein reveals a unique nuclear localization in acute myeloid leukemia with inv(16)(p13q22),”
    11. (1988). H a r b o u r ,S .L .L a i ,J .W h a n g - P e n g ,A .F .G a z d a r
    12. (1989). H o n g ,H .J .S .H u a n g ,H .T oe ta l . ,“ S t r u c t u r eo f the human retinoblastoma gene,”
    13. Human papillomavirus in oropharyngeal squamous cell carcinomas in Korea: use of G1 cycle markers as new prognosticators,” Head Neck.
    14. (2007). Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer,”
    15. (2010). Mantle cell lymphoma 12 years after allogeneic bone marrow transplantation occurring simultaneously in recipient and donor,”
    16. (2007). MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3
    17. (2009). Metastatic squamous cell carcinoma of the vulva to the lung confirmed with allelotyping,”
    18. (1993). Molecular characterization of the retinoblastoma susceptibility gene,”
    19. (1988). o k o t a ,T .A k i y a m a ,Y .K .T .F u n ge ta l . ,“ A l t e r e de x p r e s s i o n of the retinoblastoma (RB) gene in small-cell carcinoma of the lung,”
    20. (2006). Olivella et al., “p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas,”
    21. (2000). Ovarian cancer cells that coexpress endogenous Rb and p16 are insensitive to overexpression of functional p16
    22. (2001). Overexpression of the cell cycle inhibitor p16INK4A in high-grade prostatic intraepithelial neoplasia predicts early relapse in prostate cancer patients,”
    23. (1999). Overexpression of the cyclin-dependent kinase inhibitor p16 is associated with tumor recurrence in human prostate cancer,”
    24. (2010). p16INK4 expression in basal-like breast carcinoma,”
    25. (2004). Promoter hypermethylation and protein expression of the p16 gene: analysis of 43 cases of B-cell primary gastric lymphomas from China,” Modern Pathology,v o l .1 7 ,n o .4 ,p p .
    26. (2009). Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers,”
    27. (1995). Retinoblastoma-proteindependent cell-cycle inhibition by the tumour suppressor p16,”
    28. (1984). Retinoblastoma: clues to human oncogenesis,”
    29. (1990). Role of the retinoblastoma gene in the initiation and progression of human cancer,”
    30. (1989). T.Takahashi,M.M.Nau,I.Chibaetal.,“p53:afrequenttarget for genetic abnormalities in lung cancer,”
    31. (2000). The hallmarks of cancer,”
    32. (2001). The Rb/E2F pathway and cancer,”
    33. (1996). The retinoblastoma gene product is a negative modulator of the apoptotic pathway,”
    34. (2005). The role of the retinoblastoma protein (Rb) in the nuclear localization of BAG-1: implications for colorectal tumour cell survival,”
    35. (1996). Wild-type and mutant retinoblastoma protein in paraffins e c t i o n s ,

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.