Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases.

Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients' life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients' samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.