TITLE:
Evaluation of the BRCA1/2 mutation as a prognostic marker in primary peritoneal serous cancer
AUTHORS:
Naoto Furukawa, Sumire Ohno, Takahiko Kasai, Sachiko Morioka, Fuminori Ito, Yasuhito Tanase, Shoji Haruta, Seiji Kanayama, Ryuji Kawaguchi, Shozo Yoshida, Hiroshi Kobayashi
KEYWORDS:
BRCA1; Primary Peritoneal Serous Cancer; Prognosis
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.3 No.9,
November
7,
2013
ABSTRACT: Introduction: The present study was a retrospective investigation of the relation between immunohistochemical BRCA1/2 status and prognosis in patients with primary peritoneal serous cancer (PPSC). Materials and Methods: We retrospectively evaluated 14 consecutive patients diagnosed with PPSC other than hereditary breast and ovarian cancer between 2005 and 2010. All patients had serum CA125 levels >40 U/mL prior to starting first-line chemotherapy with paclitaxel and carboplatin. Paclitaxel was administered as a 3-hour intravenous infusion at a dose of 175 mg/m2 on day 1, and carboplatin was delivered at an area under the curve of 5 based on the Calvert method. Patients received six cycles of first-line chemotherapy, except patients whose disease was determined to be progressive during the chemotherapy regimen. BRCA1/2 and p53 protein expression was determined by immunohistochemistry of patient tissue samples. The Cox proportional hazards model was used to evaluate univariate and independent multivariate associations with the effect of clinical parameters, such as age at diagnosis; tumor histology; tumor grade; and rate of change in CA125, and BRCA1/2, p53 status on overall survival. Probability values of less than 0.05 were considered to indicate statistical significance. Results: Two cases (14%) had the BRCA1 mutation, and none had the BRCA2 mutation. Eleven cases (79%) were positive for p53. In the univariate analysis, factors significantly associated with overall survival were (pre-chemotherapy CA125-pre-2nd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0034) and (pre-chemotherapy CA125-pre-3rd chemotherapy CA125)/pre-chemotherapy CA125 (p = 0.0245). BRCA1 and p53 status were not predictors of overall survival. Multivariate analysis performed with overall survival as an endpoint revealed that none of the factors examined was significant. Median survival rate of patients without a BRCA1 mutation was 23.5 months (2 - 82 months), and all died. By contrast, one patient with a BRCA1 mutation remains alive at 85 months, and the other patient died at 64 months. Conclusion: BRCA1 might be a predictor of overall survival in patients with PPSC receiving chemotherapy.