title: Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube.
abstract: 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 examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered 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. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.
authors.affiliation: Department of Pathology, University of Southern California School of Medicine, Los Angeles, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: C J
authors.initials: CJ
authors.lastname: Sung
authors.forename: P
authors.initials: P
authors.lastname: Cao
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Cai
authors.forename: T A
authors.initials: TA
authors.lastname: Godwin
authors.forename: E E
authors.initials: EE
authors.lastname: Kramer
authors.forename: S C
authors.initials: SC
authors.lastname: Lauchlan
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics*; D005185:Fallopian Tube Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012680:Sensitivity and Specificity