Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors

Purpose: We studied the prognostic and predictive value of immunohistochemi cally detected occult tumor cells (OTCs) in lymph nodes and bone marrow asp irates obtained from node-negative breast cancer patients. All were classif ied as distant metastases-free using conventional staging methods. Patients and Methods: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N0M0 breast cancer and a single affected lymph node partic ipated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs usi ng monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological find ings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. Results: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in th e bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6 .4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 p atients with pT1-2N0M0 breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tu mor cells increased with the following tumor features: larger size, poor di fferentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-I concentrat ions. Patients with detected OTCs showed reduced disease-free survival (DFS ) and overall survival (OAS) rates that were comparable to those observed i n patients who had one positive lymph node. Multivariate analysis of progno stic factors revealed that OTCs, histalogical grading, and tumor size are s ignificant predictors of DFS; OTCs and grading of GAS. Conclusions: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pat hways. Although OTCs were significantly more frequent in patients with othe r unfavorable prognostic factors, they were confirmed as an independent pro gnostic factor for pT1-2N0M0, RO breast cancer patients.