EARLY OCCURRENCE AND PROGNOSTIC-SIGNIFICANCE OF P53 ALTERATION IN PRIMARY-CARCINOMA OF THE FALLOPIAN-TUBE

The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood, Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examin e the efficiency of immunohistochemistry (IHC) in detecting p53 altera tion in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examin ed for p53 alteration by IHC and polymerase chain reaction-single-stra nd conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was u sed to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characterist ics were analyzed by two-tailed Fisher's exact tests. IHC correlated w ell with PCR-SSCP with 100% sensitivity and 83.39% specificity for det ecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showe d p53 alteration. Alteration of p53 occurred in all stages of PCFT wit h a similar incidence in carcinoma in situ and late-stage disease. Alt eration of p53 was related to tumor histologic type. Significant survi val difference was noted between advanced and early clinical stages bu t no such difference was identified among different tumor grades. Comp ared to the p53-nonaltered group, the presence of p53 alteration in PC FT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patien ts with residual tumor after surgery, those with p53-altered tumors ha d a significantly decreased survival compared to those with p53-nonalt ered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Short er survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an earl y event in tubal tumorigenesis and may play an important role in the d evelopment of PCFT. Whether detection of p53 alteration may serve as a n indicator of high-risk patients for whom more aggressive adjuvant ch emotherapy may be considered needs to be explored in the future. (C) 1 997 Academic Press