Document Detail

Loss of p16 expression has prognostic significance in human nasopharyngeal carcinoma.
MedLine Citation:
PMID:  12796384     Owner:  NLM     Status:  MEDLINE    
PURPOSE: p16 is an important inhibitor of cell cycle progression; absence of p16 can thus result in increased cellular proliferation. In nasopharyngeal carcinoma (NPC), absence of p16 has been reported in association with presence of the EBV and pRb. We therefore examined p16, pRb, and EBV-encoded RNA (EBER) expression in biopsy specimens from 84 patients with newly diagnosed NPC, who were treated primarily with curative radiation therapy. Our objective was to determine whether there was a correlation between these parameters and clinical outcome in NPC. EXPERIMENTAL DESIGN: Sections were cut from archival formalin-fixed, paraffin-embedded tumor blocks from NPC patients. p16 and pRb expression were determined using polyclonal and monoclonal antibodies, respectively. The presence of EBV was determined by in situ hybridization for EBER. The percentage of positively staining tumor nuclei was scored for p16 or pRb immunoreactivity. Relative intensity and proportion of cells with EBER signals were also documented. RESULTS: p16 expression was reduced (</=5% positive immunoexpression) in 59 of 84 (70%) NPC samples; in contrast, pRb was observed in all (100%) tumors. EBER signals were detected in 67 of 83 (81%) NPC specimens. There was a weak correlation between EBER presence and loss of p16 (P = 0.1). Using a Cox regression model controlling for known prognostic parameters, such as age, weight loss, and tumor stage, complete absence of p16 expression (0%, i.e., no immunostaining identified throughout the specimen) was associated with an inferior overall survival rate (P = 0.022). In addition, EBER-positive NPC was strongly associated with improved overall survival (P = 0.005) as reported previously (Shi et al., Cancer, 94: 1997, 2002). CONCLUSION: These results provide the first evidence suggesting that inactivation of p16 appears to be a significant predictor for poor overall survival in NPC. Given that reduced p16 expression is observed in the majority of patients with NPC, this indicates that therapeutic strategies targeting the p16 pathway may be a biologically rational approach for NPC. The favorable prognostic value of EBER suggests that future clinical trials with NPC should consider stratifying for EBER status.
Antti A Mäkitie; Christina MacMillan; James Ho; Wei Shi; Andrew Lee; Brian O'Sullivan; David Payne; Melania Pintilie; Bernard Cummings; John Waldron; Padraig Warde; Jonathan Irish; Dale Brown; Ralph Gilbert; Patrick Gullane; Fei-Fei Liu; Suzanne Kamel-Reid
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  9     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-10     Completed Date:  2004-01-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2177-84     Citation Subset:  IM    
Department of Otolaryngology, Princess Margaret Hospital/Ontario Cancer Institute, Toronto M5G 2M9, Canada.
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MeSH Terms
Cyclin-Dependent Kinase Inhibitor p16 / analysis*
Disease-Free Survival
Herpesvirus 4, Human / genetics
Middle Aged
Nasopharyngeal Neoplasms / chemistry*,  mortality,  virology
RNA, Viral / analysis
Retinoblastoma Protein / analysis
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/RNA, Viral; 0/Retinoblastoma Protein

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