P53 AND BCL-2 PROTEINS AS PROGNOSTIC MARKERS IN HUMAN PAPILLOMAVIRUS-ASSOCIATED CERVICAL LESIONS

Purpose: The present study wets designed to analyze the expression of p53, mdm2, and bcl-2 proteins, with special emphasis on their associat ion with the grade of squamous intraepithelial lesion (SIL), human pap illomavirus (HPV) type, and clinical course of the disease. Special at tention was focused on the value of individual protein expressions, as well as combined p53/mdm2 and p53/bcl-2 phenotypes, in predicting the clinical course of cervical lesions. Materials and Methods: The expre ssion of p53, mdm2, and bcl-2 was studied immunohistochemically in a s eries of 98 HPV lesions of the uterine cervix. Results: Frequent expre ssion of p53, mdm2, and bcl-2 proteins was found in the cervical lesio ns. However, only p53 expression independently provided information fo r prediction of the clinical course of HPV lesions, High levels of p53 expression were detected in most low-grade SILs (LSILs) (83%) and HPV 6/11/42-associated lesions (86%). In high-grade SILs (HSILs) positive for high-risk HPV types, p53 expression was frequently either totally absent or it only occurred in a few scattered cells, These lesions we re closely associated with disease progression. The evaluation of bcl- 2 expression alone was not useful for predicting clinical outcome, alt hough abnormal bcl-2 expression in suprabasal layers was more common i n HSILs, By contrast, the combined p53/bcl-2 phenotype, which showed a low percentage of p53-positive cells with bcl-2 overexpression in upp er epithelial layers, was found to be involved in the progression of H PV lesions. Conclusion: The present study showed that HPV lesions with a high percentage of cells that express p53 are more likely to regres s than those with low or absent p53, p53 thus seems to hold promise as a molecular marker for the risk of the progression of HPV-associated SILs. In addition, the assessment of p53 and bcl-2 expression patterns may be useful to predict the clinical course of cervical HPV lesions.