p53 codon 72 polymorphism and its overexpression in patients with laryngeal carcinoma: Prognostic implications.
Abnormalities in the p53 gene are the most common genetic alterations seen in laryngeal carcinoma. No data exist regarding the association between laryngeal carcinoma and a distinct codon 72 variant and its expression. We conducted a prospective study (1) to analyze the p53 codon 72 polymorphic variants in patients with laryngeal carcinoma, (2) to analyze the expression of p53 mRNA in tissues of patients with laryngeal carcinoma using the reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and (3) to detect p53 antibodies in the plasma of patients with laryngeal carcinoma before and after treatment. Tissue and blood samples were taken from 40 patients with laryngeal carcinoma-36 men and 4 women, aged 40 to 65 years (mean: 56)-and 20 age-matched controls with laryngeal conditions other than carcinoma. RT-PCR was used to measure p53 mRNA expression, and PCR-restriction fragment length polymorphism was used to determine p53 polymorphism. In addition, p53 antibodies were detected in plasma by Western blot testing. The 40 patients were treated with either surgery (total laryngectomy or conservation surgery) or radiotherapy. Tissue and blood samples were analyzed before treatment and 4 weeks after treatment. The findings were compared with those of the 20 controls. The results revealed that (1) homozygosity of the Pro72 variant of p53 was present in 26 laryngeal carcinoma patients (65%), (2) heterozygosity for the Pro/Arg genotype was present in 13 patients (32.5%), and (3) the Arg72 variant of the p53 allele was present in 1 patient (2.5%) before treatment. Overexpression of p53 mRNA was found in all patients with laryngeal carcinoma and in none of the controls before treatment; the difference was approximately 3.3 folds higher in the carcinoma group. However, p53 expression was not related to the biologic aggressiveness of these tumors. It is interesting that 4 weeks after definitive therapy, the expression levels of p53 mRNA in the 40 patients were comparable to those of the controls. The p53 antibodies were detected in the plasma of all patients with laryngeal carcinoma prior to definitive therapy and in none of them afterward, indicating that these antibodies represent a prognostic marker in laryngeal carcinoma. Our findings suggest that there is a correlation between p53 overexpression and the development of laryngeal carcinoma. Anti-p53 antibodies can be used as a prognostic marker in laryngeal carcinoma, and they can be exploited in the future to control the response to therapy and to monitor for certain early recurrences before they become clinically detectable.
Department of Otolaryngology-Head and Neck Surgery, PGIMER, R-31/Level 2, Block F, Chandigarh 160012, India.
Gopika
G
Kalsotra
Ashok K
AK
Gupta
Rijuneeta
R
Gupta
Ritu
R
Rathi
Rajender
R
Prasad
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000628:therapy; D007825:Laryngectomy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D011878:Radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology
D001323:Autoantibodies; D003062:Codon; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53