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

Abstract

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.

Mammaglobin-A Expression Is Highly Specific for Tumors Derived from the Breast, the Female Genital Tract, and the Salivary Gland

“…At least 11 studies involving 30–1017 patients have earlier analyzed the prognostic relevance of mammaglobin-A expression in breast cancer. Among these, three found a poor prognosis of tumors with high mammaglobin-A expression [ 20 , 41 , 42 ], five reported a poor prognosis of tumors with low mammaglobin-A expression [ 25 , 43 , 44 , 45 , 46 ], and three did not find a link between mammaglobin expression and patient outcome [ 47 , 48 , 49 ]. The fact that we were unable to find a significant association between mammaglobin-A expression and patient outcome in 1139 cases of invasive breast cancer of homogeneous histologic subtype (all NST) might suggest that mammaglobin-A expression is not a critical prognostic feature in breast cancer.…”

“…Due to its preferential expression in breast epithelial cells, mammaglobin-A immunohistochemistry has become an established diagnostic tool for recognizing metastatic breast cancer tissue [ 19 , 20 ]. However, the accumulated data on the prevalence of mammaglobin-A expression in tumors are controversial.…”

Intercepting Premalignant, Preinvasive Breast Lesions Through Vaccination

“…Peripheral blood and tumor tissue from DCIS and IBC patients analyzed by RT-PCR identified mammaglobin expression as the most specific molecular marker for hematological dissemination of BC cells, compared to EGFR and cytokeratin 19 ( 76 ). Mammaglobin protein and mRNA expression have been detected in 75–80% of primary and metastatic BC, as well as in bone micrometastases of BC ( 77 ). Abundance of this marker in tumor tissue and inherent immunogenicity make mammaglobin a promising target for therapy development.…”

ATP6AP1 is a potential prognostic biomarker and is associated with iron metabolism in breast cancer

“…Cancer antigen 15-3 (CA15-3) is used as a biomarker for relapse and therapeutic efficacy in patients with breast cancer ( Liu et al, 2021 ). However, the reliability of this method is unsatisfactory ( Talaat et al, 2020 ). Hence, it is imperative to screen novel biomarkers to predict prognosis, monitor metastasis, identify therapeutic targets, and investigate the potential mechanisms of breast cancer.…”