Journal of Clinical Oncology, Vol 14, 2120-2130, Copyright © 1996 by American Society of Clinical Oncology
p53 and bcl-2 proteins as prognostic markers in human papillomavirus- associated cervical lesions
K Kurvinen, K Syrjanen and S Syrjanen
MediCity Research Laboratory, Faculty of Medicine, University of Turku, Finland. anna-kaisa.kurvinen@utu.fi
PURPOSE: The present study was designed to analyze the expression of p53,
mdm2, and bcl-2 proteins, with special emphasis on their association with
the grade of squamous intraepithelial lesion (SIL), human papillomavirus
(HPV) type, and clinical course of the disease. Special attention 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 expression of p53, mdm2, and
bcl-2 was studied immunohistochemically in a series of 98 HPV lesions of
the uterine cervix. RESULTS: Frequent expression of p53, mdm2, and bcl-2
proteins was found in the cervical lesions. However, only p53 expression
independently provided information for 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 were closely associated with disease progression. The
evaluation of bcl-2 expression alone was not useful for predicting clinical
outcome, although abnormal bcl-2 expression in suprabasal layers was more
common in HSILs. By contrast, the combined p53/bcl-2 phenotype, which
showed a low percentage of p53- positive cells with bcl-2 overexpression in
upper epithelial layers, was found to be involved in the progression of HPV
lesions. CONCLUSION: The present study showed that HPV lesions with a high
percentage of cells that express p53 are more likely to regress 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.
