Comparison of Molecular Analysis and Histopathology for Axillary Lymph Node Staging in Primary Breast Cancer: Results of the B-CLOSER-I StudyVegué, Laia Bernet MD, PhD*; Rojo, Federico MD, PhD†; Hardisson, David MD, PhD‡; Iturriagagoitia, Alicia Córdoba MD, PhD§; Panadés, Ma José MD, PhD∥; Velasco, Ana PhD∥; Bonet, Eugeni López MD, PhD¶; Muñoz, Rafael Cano MD, PhD#; Polo, Luis MD, PhD**; for the B-CLOSER-I InvestigatorsAuthor Information *Department of Pathology, Hospital Lluís Alcanyís, Xativa #Department of Pathology, Hospital de la Ribera, Alzira, Valencia †Fundación Jiménez Díaz ‡Department of Pathology, Hospital Universitario La Paz, Faculty of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid §Department of Pathology, Hospital de Navarra, Pamplona ∥Department of Pathology, Hospital Universitari Arnau de Vilanova, Lleida ¶Department of Pathology, Hospital Universitari Dr Josep Trueta, Girona **Department of Pathology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain B-CLOSER-I was funded by a grant from Sysmex España S.L. The sponsor had no role in study design or in the collection, analysis, or interpretation of the data. All authors had full access to the data and the corresponding author was responsible for the final decision to submit the article for publication. The authors declare no conflict of interest. B-CLOSER-I Investigators: L. Bernet Vegué, M. Martínez, F. Sevilla Chica (Hospital Lluís Alcanyís, Xativa, Spain); F. Rojo (Fundación Jiménez Díaz, Madrid, Spain); D. Hardisson, A. Suárez (Hospital Universitario La Paz, Madrid, Spain); A. Córdoba Iturriagagoitia (Hospital de Navarra, Pamplona, Spain); M.J. Panadés, A. Velasco (Hospital Universitari Arnau de Vilanova, Lleida, Spain); E. López Bonet (Hospital Universitari Dr Josep Trueta, Girona, Spain); R. Cano Muñoz (Hospital de la Ribera, Alzira, Valencia, Spain); L. Polo (Hospital Universitario Virgen de la Arrixaca, Murcia, Spain). Reprints: Laia Bernet Vegué, MD, PhD, Department of Pathology, Hospital Lluís Alcanyís, Crtra de Xátiva a Silla Km2, Xátiva, 46600 Valencia, Spain. (e-mail: [email protected]). Diagnostic Molecular Pathology: June 2012 - Volume 21 - Issue 2 - p 69–76 doi: 10.1097/PDM.0b013e318241117b Buy Metrics Abstract In breast cancer, the number of lymph node metastases is the strongest predictor of outcome. However, histopathology may underestimate the frequency of metastasis. Here we compare automated molecular detection of cytokeratin 19 mRNA by one-step nucleic acid amplification (OSNA) with histopathology of single tissue sections for the staging of axillary lymph nodes in patients with breast cancer. Axillary lymph nodes were collected from 55 patients with primary breast cancer and sentinel lymph node (SLN) metastases. The central 1-mm portion of each node was processed for hematoxylin-eosin staining, and the remaining tissue was analyzed by OSNA. According to OSNA, histopathology misclassified 41.8% of patients as negative for axillary node metastasis (P=0.007). Of the individual nodes considered negative by histopathology, 4.5% contained micrometastases and 2.5% contained macrometastases according to OSNA. Furthermore, 80% of micrometastases identified by histopathology were reclassified as macrometastases by OSNA. Histopathology failed to identify 81.1% of nodes shown to contain metastasis by OSNA. However, OSNA yielded no false-negative results. On the basis of OSNA results, 3 patients were reclassified to a higher pathologic stage. The number of SLN and non-SLN metastases was unrelated according to OSNA (P=0.891). These results show that, compared with molecular detection, histopathology of single tissue sections significantly underestimates the frequency of axillary node metastases. We discuss the implications of these findings in light of current recommendations on the staging of breast cancer. © 2012 Lippincott Williams & Wilkins, Inc.