Cervical squamous dysplasias and carcinomas with immunodetectable p53 frequently contain HPV.
Studies using cervical carcinoma cell lines usually show mutated p53 in cases without detectable HPV, and wild-type p53 in cases with detectable HPV. These findings suggest that loss of p53 function, either by mutation or by binding to HPV E6, is required for cervical carcinogenesis. Because mutated p53 is usually detectable immunohistochemically, one would predict an inverse relationship between the presence of HPV and detectable p53. In this study we examined 88 formalin-fixed paraffin-embedded clinical specimens of cervix for the presence of HPV and p53 expression. All cases were studied for the presence of p53 using immunohistochemical methods. The antibody used was mouse monoclonal PAb1801 (Biogenex). The presence of HPV was detected by PCR. Twenty-six specimens showed foci of p53 expression (0/7 normal, 1/8 (13%) condylomas, 1/6 (17%) CIN I, 3/7 (43%) CIN II, 6/20 (30%) CIN III, 13/22 (59%) SCC, 2/5 (40%) adenosquamous carcinomas, and 0/13 adenocarcinomas). p53 expression was more frequent in SCC than with CIN (P = 0.026). HPV was present in 15 of 24 cases with detectable p53 and 22 of 48 cases without detectable p53. No correlation was seen between HPV status and detection of p53. With the exception of one case, p53 expression was seen in less than 10% of cells. p53 expression was not detected in any of the 13 adenocarcinomas examined (P = 0.0016 vs SCC). Our results show that alterations of p53 may play a role in the pathogenesis of cervical squamous carcinoma. However, p53 expression was neither sufficient nor required for cervical carcinogenesis, irrespective of HPV status.
Mittal
K R
KR
Department of Pathology, New York University Medical Center, New York, USA.
Lin
O
O
Chan
W
W
Goswami
S
S
Demopoulos
R I
RI
D000230:Adenocarcinoma / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014412:Tumor Virus Infections / Q000175:diagnosis; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology*
D016159:Tumor Suppressor Protein p53