Role of Immunohistochemistry in Early Detection of Bone Marrow Micrometastases in Breast Cancer

Background In Egypt, breast cancer (BC) accounted for 37.7% as reported from WHO in 2008. Mammaglobin (MAM) is BC specific marker, which is almost expressed in breast epithelial cells. It is over expressed in subset of 70–80% of primary and metastatic BC tissues and can be used for identification of BC cells in bone marrow (BM). Objectives To evaluate the significance of immunohistochemical (IHC) method applied on bone marrow trephine biopsy (BMB) in increasing the detection capacity for BC micrometastases in apparently non stage‐IV patients. To compare these results with those obtained by cytological examination of BM aspirate and the different biochemical marrow investigations. Materials and Methods Thirty prospective cases, presented with different stages (0‐III) of BC and who received no chemotherapy, were selected from Alexandria Armed Forces Hospital, Egypt, during the period from March 2014 to December 2015. All patient were subjected to the following work up: Reviewing patients' medical records for all clinical and demographic data. BM cytological examination (at least 6–8 Leishman's‐stained BMA smears) was meticulously scanned for any sheets of non‐haemopoietic malignant cells. Histological examination of BM core biopsy (at least 2.5 cm long); minimum of 2 H&E stained sections were thoroughly examined by two histopathologists for any sheets of nonhaemopoietic malignant cells. Morphological interpretation was guided by the standardized morphological criteria. IHC staining was performed on the BMB sections using MAM monoclonal antibody. CA15‐3 serum and BMA plasma levels were assessed using the fully automated Abbott “Axsym” system. Results 22 patients were diagnosed with infiltrating duct carcinoma (IDC) (73.3%), while the rest (26.7%) were diagnosed with infiltrating lobular carcinoma (ILC). Three patients with IDC were classified as grade I (13.6%), 10 as grade II (45.5%), and 9 as grade III (40.9%). Regarding the stage, 2 patients (6.7%) presented with stage 0, 6 patients (20%) with stage I, 14 patients (46.7%) with stage II and 8 patients (26.7%) with stage III (Figure 1). Examination of the BM aspirates of the 30 patients were completely negative (100%), while examination of the H&E stained sections from the BMB were as follows: 5 patients (16.7%) were positive for BM micrometastases showing hypercellularity, fibrosis, inflammatory infiltration (plasma cells, macrophage and eosinophils), angiogenesis and osteoclastic hyperplasia (Figure 2), while 25 patients (83.3%) were negative. 16/30 cases (53.3%) yielded positive results for the MAM IHC staining on BMB (Figures 3 and 4). There was statistical significant differences between using MAM IHC staining and BMB H&E examination (P=0.0013). By measuring CA15.3 in both serum and BM plasma, there was no statistical significant difference regarding serum and BM plasma CA15.3. Conclusions Superiority of BMB over BMA in detection of BM micrometastatic disseminated tumor cells (DTCs) in patients diagnosed with primary BC. Combining BMB with IHC staining using MAM significantly increases the detection capacity for DTCs in the BM when diagnosing patients with primary BC. In spite of the correlation present between BM plasma and serum levels of CA15‐3, neither CA15‐3 serum levels nor BM plasma levels could be reliable markers for diagnosing or detecting early occult micrometastatic DTCs in the BM at initial diagnosis of primary BC This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .