Comparison of Molecular Analysis and Histopathology for Axillary Lymph Node Staging in Primary Breast Cancer

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.

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

“…The authors state that one-level histology was chosen to reflect the minimum standard used in many laboratories. 51 The study by Choi et al 53 reported a sensitivity of 77.8% (95% CI 60% to 90%) for OSNA, which is comparatively low. The authors indicate that this is likely to be the result of TAB; however, the dissection of the node was carried out using a similar method to that used in other studies.…”

“…Sixteen test accuracy papers were included for OSNA, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] with two papers reporting the same study. Two unpublished papers 40,66 for Metasin were identified and assessed using the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) in Table 7.…”

“…A paper by Bernet Vegue et al 51 reported on the Breast Complete Lymphadenectomy OSNA Study for Enhanced Review-I (B-CLOSER-I). Eight hospitals were involved in this single-gate study comparing histopathology and OSNA for the pathological staging of ALNs after identification of positive SLNs in patients with primary breast cancer.…”

“…The study by Bernet Vegue et al 51 reports on a single-gate study using only one-level histopathology, with the remaining tissue used for OSNA, which is likely to result in substantial TAB. The authors claim that this approach was chosen to replicate routine use.…”

“…The study by Bernet Vegue et al 51 investigated only a 1-mm central node slice by histopathology, with the remainder allocated to OSNA (therefore, a high rate of discordance was predicted). Values for sensitivity and specificity were not provided in the paper.…”