Detection of bone marrow micrometastases in breast cancer patients with flow cytometry method and correlation with other prognostic parameters

Purpose: The search for occult metastatic cells in patients with breast cancer is of considerable importance, because early dissemination of tumor cells is one of the leading causes of relapse at distant sites and of death from cancer. Immunocytochemical detection of bone marrow micrometastases has been reported as a prognostic marker in breast cancer. The aim of this study were to evaluate the potential advantage of flow cytometry as an objective method of identifying and quantifying micrometastatic deposits within bone marrow and to determine the prevalence and quantity of micrometastases in patients with breast cancer. In this study was investigate the correlation of bone marrow micrometastases with prognostic parameters (age, menopausal status, tumor size, and lymph node involvement), immunohistochemical markers and intraductal component (DCİSMatherial and Methods: We obtained bone marrow aspirates from upper iliac crests of 52 patients with stage I-IV breast cancer and 16 patients without epithelial cancer. All patients were evaluated for the presence of distant metastases with chest X-ray, abdominal ultrasound, and whole body bone scan. Epithelial cells were detected by dual staining with monoclonal anti-cytokeratin and both propidium iodide and CD45. The cells were analyzed (105 events) using on flow cytometerResults: Cytokeratin-18 positive cells were detected in the bone marrow specimens of 2 of the 16 control patients without epithelial cancer (12.5 percent) and 11 of the 52 patients with breast cancer (21 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis, tumour size, stage, menopausal status, hormone receptor status, histologic grade, expression of c-erb-B2, tumor subtype, lymphovascular invasion, intraductal component (DCİS) and sex. Mean age of the study subjects was 46.6 (min 27 and max 82). Forty-four patients had invasive ductal carcinoma proven histologically. Twenty-eight patients were premenopausal and 22 were postmenopausal. Tumor size was less than 2 cm in 21, 2 to 5 cm in 24, and larger than 5 cm in 6 patients. In 22 subjects axilla was free of lymphatic metastases, 1 to 4 nodal involvement was detected in 9, 4 to 9 nodal metastases was observed in 12, and more than 9 nodal metastases was detected in 11 women. ER was positive in 40, and PR was positive in 35 subjects. Expression of c-erbB2 was positive in 38. Four cases had grade I tumor, 22 had grade II, and the remaining 26 had grade III tumor. DCİS was detected in 25 cases. Positive CK-4 expression was detected in one patient and EpCAM exspression in 3 patients. Bone marrow micrometastases significantly correlated with age and metastases in bone, bone marrow, lung and liverConclusion: It is concluded that bone marrow micrometastases correlates with the age and metastases in bone, bone marrow, lung and liver in breast carcinoma patients.