The prognostical importance of BRCA1 and BRCA2 protein expression in breast, ovary and tube carcinomas: immunohistochemical and clinicopathological study

ABSTRACTGermline mutations in BRCA1 and BRCA2 tumor suppressor genes increase thesusceptibility to breast, ovarian and tubal carcinomas and are responsible in about 25% ofhereditary breast-ovary syndromes.The aim of this study is detection of gene products of BRCA1 and BRCA2 in breast,ovary, and fallopian tube cancers in younger patients using the immunohistochemicaltechnique and to search the probable correlation between the results and the tumors? biologicalbehavior and grade.Forty-eight breast, 49 ovarian and 4 tubal carcinomas diagnosed at age of 50 or belowincluded in this study. For BRCA1 two different antibodies directed to C and N terminal endswere used. Using BRCA1 (Neomarker) antikor, antigenic loss was detected in 70% of theovarian tumors of deceased patients. In all Stage IV deceased patients, the tumors showednuclear antigenic negativity. Using the same antikor, no correlation was detected between thetumor grade and immunostaining status. In ovarian carcinomas, the tumors from Stage III andIV deceased patients stained weakly and focally for BRCA2. All the fallopian tube carcinomaswere negative or focally positive for the same antikor. In deceased breast tumor patients, anantigenic loss was present in 75% of the cases. These features supported the potentialprognostic significance of BRCA2 in breast, ovary and fallopian tube carcinomas.Using BRCA1 (Dako) antikor, the evaluation of the intensity of the immunostainingdetect no correlation between the stage and the life status of the patients and grade of thetumor in all groups. Seven cases of ovarian serous borderline tumors showed diffuseimmunoreaction for all three antibodies.In general, immunostaining patterns observed in this study showed that nuclearimmune reaction for BRCA1 and BRCA2 represents a physiological phenotype and isassociated with a better prognosis, whereas, antigenic loss for these proteins is common inhigh grade tumors and can be used as a bad prognostic feature. The correlation of thesefindings with molecular techniques can lead important data.Key Words: Hereditary breast-ovarian cancer syndrome, BRCA1, BRCA2 andimmunohistochemistry.