[Cervix dysplasias: study of Rb and p53 gene expression and correlation with mitotic activity].
OBJECTIVE
Certain HPV types have transforming properties. These oncogenic activities are related to the abilities of the viral proteins E6 and E7 to inhibit the products of two cellular tumor suppressor genes (p53 and Rb respectively). But the early steps of cervical carcinogenesis are not well known. The goal of our study was to evaluate cervical intraepithelial neoplasia (CIN) for the tumor suppressor genes p53 and pRb, the HPV status and the mitotic activity, in order to better understand the mechanism of carcinogenesis.


METHODS
Twenty formalin-fixed paraffin-embedded cone biopsies were selected because they contained adjacent to normal epithelium different grades of CIN. Immunohistochemistry was performed for evaluation of PCNA, pRb and p53. Expression of these different biomarkers was assessed with the help of an image analysis system, in the different epithelial layers of the different normal and pathological cervical areas. The results were compared to normal controls.


RESULTS
There is an increase of PCNA expression in normal epithelium adjacent to CIN, compared to normal controls. As tissues progress from adjacent normal epithelium to condylomatous lesion and to the different grades of CIN, PCNA expression increases (mainly in the superficial epithelial layers). For p53 and pRb, the expression is increased in the basal and parabasal layers of adjacent normal epithelium and condylomatous lesions. The observance of histologic signs of CIN is associated with a disappearance of p53 and pRB expression.


CONCLUSIONS
These results indicate that the early steps of cervical carcinogenesis involve proliferative dysregulation in relation to the p53 and pRb modulatory mechanism. So expression of viral proteins of HPV is probably the earlier step of carcinogenesis in cervical carcinoma.
Mathevet
P
P
Clinique gynécologique, hôpital Edouard-Herriot, Lyon, France.
Frappart
L
L
Hittelman
W
W
D019092:Conization; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005260:Female; D015870:Gene Expression; D016161:Genes, Retinoblastoma / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008938:Mitosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D002578:Uterine Cervical Dysplasia / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*
D018809:Proliferating Cell Nuclear Antigen