The investigation of DNA repair polymorphisms with histopathological characteristics and hormone receptors in a group of Brazilian women with breast cancer.

The association of tumor differentiation and estrogen receptor expression with the prognosis of breast cancer has been well established. Nevertheless, little is yet reported about the association of morphological characteristics of the tumor, estrogen receptor status and polymorphisms in low penetrance genes. The aim of the present study was to investigate a possible association between DNA repair gene polymorphisms (XRCC1, XPD, XRCC3, and RAD51) with histological type, grade and hormone receptor expression in a series of breast cancers. A cross-sectional study was carried out to evaluate 94 women with breast carcinoma, who had already been selected and included in a study on the association of DNA repair gene polymorphisms. For immunohistochemistry, formalin-fixed, paraffin-embedded tissue samples from breast tumors were consecutively retrieved from the histopathology files of our institution. DNA obtained from blood samples of the same patients was investigated for the presence of the following polymorphisms: Arg-399Gln located in the XRCC1 gene; 135C/G located in the RAD51 gene; Lys751Gln located in the XPD gene and Thr241Met located in the XRCC3 gene. Polymorphisms were considered to be independent variables and hormone receptor expression and the morphological characteristics of the tumors comprised the dependent variables. No statistically significant association was found between gene polymorphisms and hormone receptor status. The association between XRCC1-Arg399Gln polymorphism and ductal carcinoma was statistically significant (P = 0.02). The association of the XPD-Lys751Gln polymorphism with histological grade was also tatistically significant (p = 0.05). In conclusion, the XRCC1 genotype was found to be associated with ductal carcinoma histotypes and XPD genotype with low histological grade, which is the most frequent pattern of sporadic breast carcinomas.

HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by immunohistochemistry and fluorescence in situ hybridization.

The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.