p53 mutations in cervical carcinogenesis--low frequency and lack of correlation with human papillomavirus status.
p53 gene aberrations are common in human malignancies, and recent studies suggest that in cervical carcinoma p53 function is inactivated either by complex formation with human papillomavirus (HPV) E6 product or by gene mutation. Using polymerase chain reaction (PCR) followed by denaturing gradient gel electrophoresis (DGGE), we examined the mutational status of the four 'hotspot' regions of the p53 gene in 47 primary cervical carcinomas. HPV status was determined, also by PCR. In 20 of these cases, we examined for loss of heterozygosity (LOH) on chromosome 17p13. In the 47 carcinomas, and in a further 68 biopsy specimens from normal, premalignant and malignant cervix, we investigated aberrant immunocytochemical expression of p53. Immunocytochemically, abnormal p53 expression was detected in 13 of 115 cases (8/57 carcinomas). Somatic mutation in p53 was detected in 1 of 47 cervical carcinomas; 36 were positive for HPV 16, 18 or 33. A low level of allele loss (3 out of 20 cases) was detected on chromosome 17p, occurring in both HPV-positive and HPV-negative cases, and in cases with and without p53 mutations. We conclude that somatic mutation in the hotspot regions of the p53 gene occurs infrequently in cervical carcinomas; that immunocytochemically detectable levels of p53 are also infrequent; and that there is no consistent correlation between p53 mutational status, LOH on chromosome 17p or HPV status in these cancers.
Busby-Earle
R M
RM
Department of Pathology, Edinburgh University Medical School, UK.
Steel
C M
CM
Williams
A R
AR
Cohen
B
B
Bird
C C
CC
D000230:Adenocarcinoma / Q000235:genetics; D018196:Carcinoma, Adenosquamous / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D004252:DNA Mutational Analysis; D015344:DNA Probes, HPV; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*
D015344:DNA Probes, HPV; D016159:Tumor Suppressor Protein p53