Document Detail


Prognostic significance of p16INK4a alterations and 9p21 loss of heterozygosity in locally advanced laryngeal squamous cell carcinoma.
MedLine Citation:
PMID:  12124774     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting as a tumor suppressor. Genetic alterations involving the 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median of follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) has been studied prospectively. Our purpose was to investigate p16 alterations (9p21 allelic loss, hypermethylation and point mutations) and their possible association with clinico-pathological data and flow cytometric variables (DNA-ploidy and S-phase fraction (SPF)), and to determine the possible prognostic role of this gene in these tumors. PCR-based techniques were used for investigating 9p21 loss of heterozygosity (LOH) and methylation promoter status of the p16 gene. p16 mutations were detected by PCR-SSCP (single strand conformation polymorphism) and sequencing. 9p21 LOH was detected in 16/62 (26%) informative tumors, point mutations in 5% (3/64) and hypermethylation in 9% (6/64) of the cases. p16 alterations were significantly associated with high SPF and DNA-aneuploidy. By univariate analysis, poor histologic differentiation, stage IV, DNA-aneuploidy and p16 point mutations proved to be significantly related to quicker relapse, whereas these same factors, and in addition high SPF, 9p21 LOH and any p16 alterations were significantly related to shorter overall survival. By Cox proportional hazards analysis only histologic grade (G3) and p16 point mutations were independently related to both disease relapse and death. Our study has identified p16 point mutations as important biomolecular indicators in LSCCs.
Authors:
Viviana Bazan; Ines Zanna; Manuela Migliavacca; Maria Teresa Sanz-Casla; Maria Luisa Maestro; Simona Corsale; Marcella Macaluso; Gabriella Dardanoni; Salvatore Restivo; Paloma López Quintela; Ricardo Bernaldez; Sergio Salerno; Vincenza Morello; Rosa Maria Tomasino; Nicola Gebbia; Antonio Russo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  192     ISSN:  0021-9541     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-07-18     Completed Date:  2002-08-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  286-93     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Section of Molecular Oncology, University of Palermo, Italy.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Carcinoma, Squamous Cell / genetics*,  pathology
Chromosomes, Human, Pair 9 / genetics*
DNA Methylation
DNA, Neoplasm / chemistry,  genetics
Genes, p16*
Humans
Laryngeal Neoplasms / genetics*,  pathology
Loss of Heterozygosity
Multivariate Analysis
Ploidies
Point Mutation
Prognosis
Proportional Hazards Models
Prospective Studies
S Phase
Chemical
Reg. No./Substance:
0/DNA, Neoplasm

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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