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BRCA2 Reversion Mutation-associated Platinum Resistance After NACT-IDS In Epithelial Ovarian Cancer

Posted on:2016-08-22Degree:MasterType:Thesis
Country:ChinaCandidate:Z YuFull Text:PDF
GTID:2284330461969897Subject:Oncology
Abstract/Summary:PDF Full Text Request
Background:Epithelial Ovarian Cancer(Epithelial Ovarian Cancer, EOC) is one of the most common malignant tumor of female reproductive system, with high recurrence rate, poor prognosis of clinical features. When the initial treatment, about 70% of the patients with ovarian cancer is sensitive to platinum based chemotherapy.However, there are 65%-75% in patients with recurrent ovarian cancer on platinum based chemotherapy without reaction or resist, this is cause ovarian cancer chemotherapy is one of the important reasons for the failure and worse prognosis.Acquired drug resistance is a major obstacle to resolve in ovarian cancer treatment, but its mechanism has not been elucidated.Many scholars have carried on the thorough research, found that breast cancer susceptibility gene 2 reversion mutation might be one of the main reasons for ovarian cancer drug resistance.However, reply BRCA2 mutations in ovarian cancer is related to whether the acquired platinum resistance, as well as the influence on the prognosis of patients with the existence, no clinical research at present.This experiment aims to detect BRCA2 mutations in patients with ovarian cancer and back mutation situation, and through the statistical analysis to study whether reply BRCA2 mutations associated with survival of patients with prognosis and provide experimental basis for new clinical treatment strategy and direction.Methods:1, En Vison two step immunohistochemical method to detect the 72 cases of ovarian tissue specimens, all pathological examination of ovarian serous carcinoma, another 1 case of normal fallopian tube, paramesonephric duct cyst in 1 case, as control. N-terminal and C-terminal antibodies are used to visualize protein truncation by demonstrating that the beginning of the protein is present but the end(ie, terminus) is absent. 2, collecting 72 cases of patients with ovarian cancer related clinical data, including age, FIGO stage, pathological type, Histological grade, Malignant cells in ascites or hydrothorax, Liver, lung or Vaginal metastasis, Lymph node metastasis, Residual tumor and recurrent time.3, According to the patients with or without preoperative chemotherapy can be divided into primary debulking surgery group(PDS)and neoadjuvant chemotherapy with interval debulking surgery group(NACT-IDS).4, Analyze whether reply BRCA2 mutations associated with prognosis in patients with, reply BRCA2 mutations and preoperative chemotherapy with or without associated platinum drugs.Results:1, In 72 cases of specimens, the resistance to BRCA2-N terminal antibodies were expressed, and express the strength has no obvious difference;BRCA2-C terminal is part of the expression.But normal fallopian tube group and paramesonephric duct cyst, expression in malignant tumor tissues in carcinoma tissues and normal ovarian tissue.2, through the correlation analysis found that BRCA2-C terminal expression and ovarian cancer ascites cancer cells positive correlation;3,Primary debulking surgery group and neoadjuvant chemotherapy with interval debulking surgery group patients with BRCA2 expression differences, and statistically significant(P = 0.028), shows that the expression of preoperative chemotherapy on BRCA2.The Kaplan-Meire survival analysis and the Cox proportional model of single factor and multiple factors analysis were performed, difference significance test the Log-Rank test.Conclusion: 1, BRCA2 in neoadjuvant chemotherapy group patients, BRCA2 reversion mutation could occur, which occurred reply BRCA2 mutations in ovarian cancer chemotherapy drug resistance of platinum.2, BRCA2 expression or not is affect the neoadjuvant chemotherapy group independent prognostic factors for patients with ovarian cancer DFS;And BRCA2 expression belongs to adverse prognostic factors.3, BRCA2 mutations and reversion mutation can be used as chemotherapy process, the detection of ovarian cancer mutations and do you have any reversion mutation, can be adjusted as the choice of chemotherapy in patients with drugs and chemotherapy regimens.
Keywords/Search Tags:BRCA2, reversion mutation, epithelial ovarian cancer, platinum resistance
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