NDLI: Retention of the Arginine Allele in Codon 72 of the p53 Gene Correlates with Poor Apoptosis in Head and Neck Cancer

Content Provider	PubMed Central
Author	Regine, Schneider-stock Christian, Mawrin Motsch, Christiane Carsten, Boltze Peters, Brigitte Hartig, Roland Buhtz, Peter Giers, Anja Rohrbeck, Astrid Freigang, Bernd Roessner, Albert
Copyright Year	2004
Abstract	The allele constitution at codon 72 of the p53 gene (CGC-arginine or CCC-proline) plays a major role in inducing apoptosis in p53 mutant cells. To verify this, we determined GC-status, p53-mutations, and p53-loss of heterozygosity (LOH) in a group of 54 squamous cell carcinomas of the head and neck (SCCHN). A novel approach, using a one-step real-time PCR analysis with fluorescent hybridization probes, was applied to detect the GC status in tumors and corresponding blood samples. p53 mutations in exons 4 to 8 were detected by PCR-SSCP-sequencing analysis. Apoptosis was determined immunohistochemically using antibodies against Fas, FasL, p53, Bcl 2, and terminal deoxy-transferase-mediated dUTP nick end labeling (TUNEL) staining. The overall frequency of p53-LOH in SCCHN was 45.2%. In cases of LOH, there was a preferential loss of the proline allele, which was associated with an up-regulation of Bcl 2 and lack of co-expression of Fas/FasL and, thus, impaired apoptosis ( P < 0.001). Apoptosis was not observed in tumors carrying the arginine allele. p53 mutations were detected in 29.6% of SCCHN and preferentially occurred at the arginine allele ( P = 0.01). p53 alterations were more frequently observed in tumors of the oral cavity, oropharynx and hypopharynx, whereas they were rare in larynx carcinomas ( P = 0.07). The p53-LOH status was not found to be significantly correlated with sex, age, TNM-status, or tumor grading. We conclude that apoptosis is correlated with the allelic status of codon 72 in SCCHN. Homozygous proline 72 appears to be an important regulator of apoptosis via the Fas/FasL pathway in SCCHN.
Related Links	http://dx.doi.org/10.1016/s0002-9440(10)63211-7
Ending Page	1241
Page Count	9
Starting Page	1233
File Format	PDF
ISSN	00029440
e-ISSN	15252191
Journal	The American Journal of Pathology
Issue Number	4
Volume Number	164
Language	English
Publisher	American Society for Investigative Pathology
Publisher Date	2004-04-01
Access Restriction	Open
Rights Holder	American Society for Investigative Pathology
Subject Keyword	Pathology and Forensic Medicine Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pathology and Forensic Medicine

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