p53 gene alterations and human papillomavirus type 16 infection in early stages of cervical carcinoma in Serbia.
OBJECTIVE
The incidence rate (age-standardized) of cervical carcinoma in Serbia is the highest in Europe. p53 is mainly inactivated at protein level in carcinomas associated with human papillomavirus (HPV) infection, such as cervical carcinomas. These tumors show low rate of p53 mutations. It is not clear if p53 mutations confer additional impact on disease prognosis. The role of polymorphic variant at codon 72 of p53 gene on patient's prognosis is controversial. The aim of this study was to determine the frequency of p53 mutations and to assess polymorphic variants of codon 72 among cervical carcinoma patients.


METHODS
53 patients, mainly FIGO stage I (n=50), with squamous cell carcinoma (n=49) were included. 30/32 (94%) patients who received adjuvant radiotherapy were followed-up (median 15 months, range 4-39). DNA was isolated by the salting out method from tumor tissue (n=53) and blood (42/53). p53 mutations were detected by PCR-SSCP (polymerase chain reaction - single-stranded conformational polymorphism) electrophoresis. Codon 72 polymorphism was assessed by the restriction fragment-length polymorphism method.


RESULTS
Six p53 mutations were detected in 5/53 (9%) patients with FIGO stage I squamous cell carcinoma (one patient had double mutations). 25/42 (60%) patients exhibited Arg/Arg genotype. HPV16 type was detected in 29/51 (57%) cervical carcinoma samples. Relapse of disease occurred in only 2 patients- both with Arg/Arg genotype and HPV16 positive. One of them exhibited p53 mutation.


CONCLUSIONS
Our results showed low incidence of p53 mutations and prevalence of Arg/Arg genotype polymorphic variant of codon 72 of p53 gene in early stages of cervical carcinoma.
Malisic
E
E
Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. eminamalisic@yahoo.co.uk
Jankovic
R
R
Majkic
M
M
Dobricic
J
J
Radulovic
S
S
D003062:Codon; D005260:Female; D016158:Genes, p53; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D011836:Radiation Tolerance; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy / Q000821:virology
D003062:Codon