Immunohistochemically Detected Lymph-Node Micrometastases in Breast Cancer and their Correlation with Prognostic Factors

The prognostic value of immunohistochemically detected micrometastases (N1a-IHC) in conventionally negative lymph nodes (N0) and its association with newer prognostic factors is controversial. Axillary lymph nodes (n= 2,528) of 159 patients with pT1–T N0 M0-breast cancer were examined for micrometastases using a monoclonal cytokeratine antibody. In addition to the histological findings, estrogen and progesterone receptors (ER, PR), S-Phase, ploidy, EGF-R, p53, Ki-67, HER-2/neu oncoprotein, cathepsin D, and p52 were investigated. The mean follow up time was 51 ± 16 months. Micrometastases were detected in 53 of 2,528 (2.1%) lymph nodes. In 18 of 159 patients (11.3%) staged as N0 by conventional histology, one or more micrometastases were detected immunohistochemically. These patients have a prognostic disadvantage compared with N0-IHC-patients significant for distant metastases-free survival; (p =.003) and for overall survival (p =.006). Differences (p <.05) between N0-IHC- and N1a-IHC-tumors were found in tumor size, ER, EGF-R, and cathepsin D. Tumor size, grading “3,” and peritumoral vessel invasion, but not the detection of micrometastases, were confirmed as independent prognostic factors in node-negative patients by multivariate Cox regression analysis. Immunohistochemically detected micrometastases in axillary lymph nodes are of prognostic importance. However, they are not independent prognostic factors, because a correlation with other prognostic factors has been proven.