Role of immunohistochemical detection of lymph-node metastases in management of breast cancer

Background This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast-cancer patients whose axillary lymph nodes were classified, by conventional metho ds, as disease free. Methods Ipsilateral lymph nodes (negative for metastases by routine histolo gy) from 736 patients (participants in Trial V of the International [Ludwig ] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immun ohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5.2). After median follow-up of 12 years, disease-free and overall surviva l were estimated by Kaplan-Meier methods. Findings Occult nodal metastases were detected by serial sectioning and hae matoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobula r and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease- free and overall survival in postmenopausal but not in premenopausal patien ts. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after cont rol for tumour grade, tumour size, oestrogen-receptor status, vascular inva sion, and treatment assignment (hazard ratio 1.79 [95% CI 1.17-2.74], p=0.0 07). Interpretation The immunohistochemical examination of ipsilateral axil lary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recom mended as a standard method of node examination in postmenopausal patients.