For tumor diagnosis, primary location, morphology, histology and cytology, as well as clinical data, are crucial. According to the literature, the sensitivity and specificity of MAG and GCDFP-15 for the detection of breast cancer vary significantly, with MAG sensitivity being 80% to 48%, and that of GCDFP-15 being 73% to 23% [9, 13, 15]. In our study, MAG sensitivity was 34%, and its specificity 83%, while the sensitivity and specificity of GCDFP-15 were 44% and 79%, respectively. While MAG sensitivity is lower than that of GCDFP-15, its positive predictive value is higher, being 83% for MAG and 76% for GCDFP-15. This shows that the inclusion of MAG antibody in the immunohistochemical panel would contribute to the detection of metastasis of breast cancer. According to the literature, CK7 antibody was positive in 25/29 cases (86%), which reveals an 83% positivity in breast cancer .
Immunomarkers in the negative control group revealed that: 1) MAG and GCDFP-15 were both positive in a case of pancreatic adenocarcinoma and another of cholangiocarcinoma. Review of the literature reports 10% of cholangiocarcinomas positive for MAG, while other source reveals MAG expression in intestinal tumors, mainly adenocarcinomas ; 2) GCDFP-15 showed positivity in a case of colorectal adenocarcinoma and another of large cell lung carcinoma. In these cases, the lack of MAG staining contributes to a higher positive predictive value, with more chances to detect metastasis of breast carcinoma. This shows that the inclusion of MAG in the immunohistochemical panel is highly convenient. 3) CK7 was positive in 20/48 of the negative controls included, which were mainly adenocarcinomas (12/48); 4) MAG is usually found in the female genital tract cells, and has been expressed in up to 77% of endometrial carcinomas (as primary tumor) [18, 19]. However, in our study, female genital tract cells were not positive for this antibody.
As shown in Table 3, the addition of MAG to a basic immunohistochemical panel (ER. PR, CK7 and GCDFP-15) is associated with lower sensitivity. The best immunohistochemical strategy seems to be number 4, which considers hormone receptors and the inclusion of MAG in a serial manner. Despite the low sensitivity of this diagnostic approach to metastatic carcinoma of breast origin, it offers high specificity (Table 3). As far as probability, the use of the immunohistochemical panel herein proposed proved categorical in only three cases, but allowed the exclusion of all the controls.
Jae-Ho et al. proposed the inclusion of MAG within the immunohistochemical panel for the detection of metastatic breast cancer . Yang et al. concluded that MAG would be a good marker to be included in an immunohistochemical panel for differentiation between lung tumors and metastatic breast cancer in the lung . MAG sensitivity was lower than that of GCDFP-15, but had a higher specificity. When combined, the whole sensitivity decreased, but an increase in specificity was observed, with no decrease in the positive predictive value. Overall, the use of the immunohistochemical panel contributes to the detection of metastasis of breast origin. Laurinavicius et al. showed the benefit of integrating digital image analysis into routine pathology, in order to determine breast ductal carcinoma immunohistochemical profiles by using multiple immunohistochemical biomarkers. Thus, the potential inclusion of MAG in these panels, as a tumors of unknown origin marker, would be promising for the diagnosis and treatment of these patients in the future [22, 23].