Abstract P1-01-09: Molecular Detection of Sentinel Lymph Node Metastases in Breast Cancer Patients: Correlation between Cytokeratin 19 mRNA Copy Number Detected by One Step Nucleic Acid Amplification (OSNA) and Risk of Metastases in Axillary Lymph Nodes

Abstract

Abstract Background: The accuracy of the OSNA assay for metastases detection in sentinel lymph nodes (SLNs) has recently been validated in our Institute and adopted as an intra-operative test for breast cancer (BC) patient management. The aims of this study in a series of early BC patients, were: 1) to correlate the copy numbers of cytokeratin 19 (CK19) mRNA with the size of nodal metastases and with the risk of additional disease in non-sentinel lymph nodes (NSLNs); 2) to investigate the relationship between SLN status with OSNA method, and conventional bio-pathological factors taking into account the molecular BC classification: luminal A, luminal B, HER2 subtype, and triple-negative; 3) to identify a subgroup of patients with positive SLN with higher risk of NSLNs metastatic involvement. Material and Methods: 750 SLNs from 580 patients were clinically processed using both OSNA assay and post-operative histology. The results of these two methods were then compared. The correlation between the size of metastases and the copy numbers of CK19 mRNA was calculated using the Spearman correlation coefficient. Complementary axillary lymph node dissection (ALND) was performed concurrently in case of OSNA assay positivity and the probability of having a positive lymph node axillary dissection was calculated by the unconditional logistic regression model. This series of BC patients were divided into four main subtypes taking in account the BC classification based on the immunohistochemistry phenotypic patterns. Results: OSNA positivity was reported in 24.6% of the patients for a sensitivity of 94.2%. Considering the 145 patients with SLN positivity the size of metastatic foci was significantly correlated to the copy numbers of CK19 mRNA. The complex relationships among the bio-pathological variables analyzed by multiple correspondence analysis (MCA) showed that the metastatic involvement of NSLNs is associated with SLNs with a high copy numbers of CK19 mRNA and HER2 subtype tumors. OSNA specificity (95%) and negative predictive value (98.4%) clearly demonstrated its reliability to guide ALND decision. Conclusions: Our results showed that OSNA is an excellent method for the detection of metastases in SLN and its adoption in our clinical practice has determined a significant improvement in the diagnosis of metastatic BC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-09.