Correlation of brca-1, brca-2 and cox-2 immunohistochemical markers with tumor differentiation and other prognostic parametres in breast carcinomas

Breast carcinomas are the most common neoplasms among the females and ranks the second after the lung carcinomas in causing death. In recent years, more and more breast carcinomas have been detected in parallel with the increasing use of mammography. In order to be able to detect them earlier we should have more information on risk factors and it is also important to identify people carrying these factors beforehand. In this study, we aimed to detect immunohistochemically BRCA-1 and BRCA-2 gene mutations which are known to be involved in familial breast carcinomas accounting approximately 10 percent of all mammary carcinomas and we also aimed to define Cox-2 staining which is reported to be helpful to predict prognosis of breast carcinoma cases and to compare it with other known prognostic parameters such as tumor differentiation and others. On slides of 63 selected cases BRCA-1, BRCA-2 and Cox-2 reagents have been applied along with other conventional immunohistochemical markers. Sixty-one cases were invasive ductal carcinoma and two were high grade ductal carcinoma in situ. Thirteen cases with invasive tumor also had in situ component within or periphery of the main tumoral mass. Cytoplasmic staining was sought when using BRCA-1 immunohistochemical marker. Forty-six cases (73%) showed no staining whereas nine cases stained focally, 6 cases (9.5%) had light and two cases (3.2%) had moderate cytoplasmic staining. Features of staining patterns have been compared with tumor grade, status of lymph node metastasis, tumor diameter and a number of immunohistochemical markers which are known to be of prognostic value, including steroid receptors, c-erbB-2, p53 and Ki-67 proliferation index. No statistically significant relationship have been found with any of these parameters. Considering that mutation means loss of expression in BRCA-1, seventy-six percent of cases appeared to have mutation hence no staining. However, it is known that among all mammary cancers familial ones constitute only ten percent. This can be attributed to the low sensitivity of BRCA-1 marker. In addition, it is known that BRCA-1 is relatively a large gene and a number of mutations appear to remain undetected. Therefore, on this gene more advanced studies should be done in an effort to manufacture new, more reliable and sensitive reagents aiming to detect mutations immunohistochemically. Only three cases (4.8%) in sixty-three cases shoed no staining with BRCA-2 and these cases were considered to have the mutant gene. Although not verified with genetic analysis this rate appears to conform to the ones reported in the literature. Few reports have been published focusing on the detection BRCA mutations immunohistochemically. Staining features of our cases appearing to have mutations were not concordant to cases that are reported in the literature and we have attributed this to lower number of cases studied. Diameter of tumor, status of lymph node metastasis and histologic grade were not found to be statistically correlated with staining features with Cox-2, a marker which is suggested to be of value in providing prognostic information about a tumor. Similarly, Cox-2 staining showed no statistically significant relationship with estrogen and progesterone receptors, p53 and Ki-67 proliferation index. However, a weak correlation was determined between Cox-2 and c-erbB-2 staining. As to survival rates; cases having tumors stained less than 50 percent with Cox-2 had an average survival rate of 90 percent whereas in cases having tumors stained more than 50 percent this rate decreased to 83.3 percent. Therefore, Cox-2 may be said to be of helpful in providing prognostic information. In conclusion, we think that in order to attain to the aims of this study larger series should be studied and new, more reliable and more sensitive reagents must be developed in an attempt to demonstrate mutations by staining tumors immunohisto-chemically.