An Immunohistochemical Study of p53 and RB Protein Expression in Normal Cervical Tissue, Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma

Lee, Chan; Sunwoo, Tae Won; Ahn, Hee Jung

Abstract

Carcinoma of the uterine cervix is the most common malignant tumor in Korean women. It is well known that carcinogenesis is a multi-step event involoving the inactivation of tumor supressor genes, such as p53 gene and RB gene. The inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins. The pRB protein regulates early cell cyle progression by controlling transit through the G1 phase of the cell cyle. The p53 tumor suppressor gene product also plays a role in cell cycle control by the transcriptional regulation of cyclin-CDK inhibitor. Cervical carcinoma is an excellent model for studying the stepwise progression of cell transformation because this is reflected morphologically by the increasing dysplasia of the squamous cells before it becomes and invasive squamous cell carcinoma. The aim of this study was to examine the expression of pRB and compared that with overexpression of p53 in a series of cervical lesions including normal tissuess, dysplasias, carcinoma in situ and carcinomas by immunohistochemical staining with monoclonal antibody to elucidate the role of these tumor suppressor genes. The result were as follows: 1. In normal cervical mucosa and CIN I , a few positively stained cells for pRB were seen in basal and parabasal layer. 2. An abnormality of pRB, loss of expression was seen in 23.8% of CIN III and in 10.8% of invasive carcinoma. 3. Overexpression of p53 was demonstrated in 14.3% of CIN III and in 59.5% of invasive carcinoma. 4. The immunoreactivity of p53 was significantly increased (p<0.05) in stage II, III than stage I , whereas downregulation of pRB and tumor stage was not correlated. 5. The immunoreactivity of p53 was significantly increased (p<0.05) in squamous cell carcinoma than in adenocarcinoma, adenosquamous carcinoma and CIN III. These result suggest that an alteration of pRB is more frequently implicated in CIN III than invasive carcinoma, whereas overexpression of p53 may be involevd in late progression of uterine cervical carcinoma.