Her2 Expression on Disseminated Tumor Cells from Bone Marrow of Breast Cancer Patients

Abstract

Background: The presence of cytokeratin (CK)-positive cells in the bone marrow (BM) of breast cancer patients is an independent prognostic marker for long-term survival. While the exact nature of these cells remains under investigation, their persistence after chemotherapy is linked to decreased survival, making them a potential therapeutic target. Targeted therapy using the her2 antibody has been shown to improve survival in breast cancer patients. We studied the her2 expression in the BM of 105 patients with CK-positive cells present and compared it with results from the primary tumor. Materials and Methods: BM cytospins were stained to detect CK-positive cells. In 105 patients with detectable CK-positive cells, additional staining with her2 antibody was performed. Using an automated imaging system, the her2 slides were evaluated based on the criteria of the International Society for Cellular Therapy. Results were correlated with the her2 status of the primary tumor. Furthermore, the presence of her2 mRNA was examined in a subset of 27 patients using RT-PCR. Results: On 22/105 (21%) cytospins with CK-positive cells, her2-positive cells could be detected. The positivity rate for RT-PCR was 15%. Her2 overexpression on the primary tumor was 26/105 (25%). Correlation with the BM status was as follows: Hercep score 0 to 1+: 79 patients, 10 with positive BM for her2 (12%). Hercep scores 2+ to 3+: 26 patients, 12 with her2-positive bone marrows (46%) (p=0.001). Conclusion: Her2-positive cells were detected in the BM of 15-21% of patients who were also CK-positive using immunocytochemistry and RT-PCR. Correlation exists between the presence of her2 on the primary tumor, the hercep score and the presence of her2-positive cells in the BM both with RT-PCR and immunocytochemistry. Despite this correlation, in 12.6% of patients with a her2-negative primary tumor, her2-positive cells could be detected in the BM.