p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Kurvinen
K
K
MediCity Research Laboratory, Faculty of Medicine, University of Turku, Finland. anna-kaisa.kurvinen@utu.fi
Syrjänen
K
K
Syrjänen
S
S
D014408:Biomarkers, Tumor / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014412:Tumor Virus Infections / Q000150:complications* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53