CLINICAL UTILITY OF THE IMMUNOCYTOCHEMICAL DETECTION OF P53 PROTEIN IN CYTOLOGICAL SPECIMENS

In the important cytopathological distinction between benign and malignant lesions, there is always a residue of suspicious cases which cannot be satisfactorily diagnosed. Overexpression of the p53 tumor suppressor gene product has been consistently correlated with p53 missense gene mutation and is associated with malignancy. Therefore, assessment of p53 expression may assist in the cytopathological diagnosis of malignancy. Immunohistological assessment of p53 expression has been performed on a prospective series of 1333 nongynecological cytological specimens in the setting of a teaching hospital group. Evaluation of p53 staining was performed without knowledge of cytological diagnosis. Resultant p53 expression data were correlated with cytological diagnosis and clinical information. Of the 999 assessable cases, 956 had a clear cytological diagnosis. In these, p53 overexpression occurred in 108 cases of which 86 were malignant lesions. Of the 838 p53-negative cases, 119 mere in bet neoplasms. The false positives were predominantly (19 of 22) reactive mesothelial proliferations, and overexpression occurred in only a small proportion of cells. While the sensitivity of p53 overexpression is low (p53 overexpression only occurring in 41.9% of tumors), the overall specificity is 97%. In the 43 cytopathologically suspicious cases, 7 were p53 positive, all of which proved to be malignant. In this prospective unselected series, we have conclusively demonstrated a close correlation between overexpression of p53 protein and neoplasia. Furthermore, me have shown the possible utility of p53 immunostaining in cytopathology. While there are important technical caveats and some cytological specimens are suboptimal for immunostaining, the data indicate that assessment of p53 is a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.