Expression Level And Clinical Application Of BRCA1 And ATM Protein In Ovarian Serous Papillary Cystadenocarcinoma

[Background and Objective] Homologous recombination (HR) was one of the important mechanisms in repair of double-strand DNA (dsDNA) breaks. HR led to error-free repair and aimed repair of DNA damage caused by UV and replication dependence. Both BRCA1 and ATM gene were important elements involved in HR repair pathway. Mutation of them could result in instability of genome and cell canceration. PARP inhibitor could inhibite function of PARP which was important in single-strand DNA break repair. PARP inhibitor could kill BRCA1- or ATM-deficient cells specially. This was called synthetic lethal. BRCA1-mutation was common in heritage ovarian cancer patients. So it might be good for target therapy of ovarian cancer that the use of PARP inhibitor. But in sporadic ovarian cancer, especial ovarian serous papillary cystadenocarcinoma, expression level of BRCA1 and ATM was little known. This study investigated the expression of BRCA1 and ATM protein which invoved in homologous recombination repair mechanism in sporadic ovarian serous papillary cystadenocarcinoma. Furthermore, we investigated the relationship between the expression level of the two proteins and clinical characters.[Method] We collected 97 ovarian serous papillary cystadenocarcinoma cases which had been confirmed by pathology after surgery in 301 hsopital from Oct 2005 to Jan 2010. There was no history of familial ovarian cancer in all of them. The expression level of BRCA1 and ATM protein were detected by immuno-histochemistry. After reviewing the data of medical record and following-up, expression level was combined with clinicopathologic parameters for statistical analysis to investigate the relationship between BRCA1 and ATM with clinico-pathologic parameters and the influence of them on the survival of ovarian cancer. [Result] 1. In the tissue of sporadic ovarian serous papillary cystadenocarcinoma rate of loss of BRCA1 and ATM protein expression were 32.0% (31/97) and 19.6%(19/97) respectively. Total rate of loss of both proteins expression was 45.4% (44/97).2. After comparing the expression of BRCA1 and ATM protein with clinicopathologic parameters, the fact was found that as pathological grade degraded the loss of the expression of BRCA1 protein increased. However, the clinical stage, patients age and menopause state had no significant effect on the expression of both two proteins.3. The 1-,3- and 5-year survival rate were 71.8%, 48.9% and 25% respectively. The median survival time of negative and positive expression of BRCA1 was 20.5 months and 24 months respectively. The one of ATM was 23 months and 17 months respectively. The median survival time of early stage (FIGOâ… /â…¡) and advance stage (FIGOâ…¢) was 34 and 23 months respectively. The one of moderately differentiated (2nd grade) and poorly differentiated (3rd grade) was 26 and 23 months. The expression level of BRCAl and ATM, clinical stage and pathological grade had no significant effect on survival rate respectively.[Conclusion] 1. Total rate of loss expression of BRCA1 and ATM protein which involve in HR repair mechanism was 45.4%. This intimated that nearly half of ovarian serous papillary cystadenocarcinoma patients perhaps got benefit from the PARP inhibitor.2. Expression of BRCA1 protein decreased as the degree of carcinomatous tissue differentiation degraded.