Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: Experience from a London Teaching Hospital

Abstract

One step nucleic acid (OSNA) is a molecular diagnostic assay for intra-operative detection of sentinel node metastases. This study compared OSNA with standard histopathology in 283 nodes from 170 patients to evaluate sensitivity, specificity and concordance of the two methods. Additional analysis was done to investigate how cytokeratin 19 mRNA copy number affects prediction of non-sentinel node positivity. OSNA sensitivity was 93.2% and specificity 95.8%. Concordance between OSNA and histology was 95.6%. In the patients who had axillary clearance, the OSNA mRNA copy number on the sentinel node had 100% negative predictive value for histologically proven metastasis. mRNA copy numbers <1400 were not associated with histologically proven metastasis in subsequent nodes at axillary clearance. OSNA is a reliable method for the intra-operative evaluation of axillary lymph node metastasis even when half of the lymph node is used. Identification of mRNA copy number threshold predicting the positivity of non-sentinel axillary nodes seems to be feasible and would be clinically important.

Total tumor load assessed by one-step nucleic acid amplification assay as an intraoperative predictor for non-sentinel lymph node metastasis in breast cancer

“…OSNA assay is a molecular-based intraoperative detection method for SLN metastases that has several advantages over frozen sections; it is a fast, standardized technique in which the entire lymph node is examined and provides quantitative results [2]. In this study, univariate analysis showed that tumor size, number of SLN macrometastases and CK19 mRNA copies (TTL) determined by OSNA assay were significantly associated with non-SLN metastases.…”

“…Combined analysis of nine studies that compared OSNA with histopathology demonstrated high concordance between both methods (96%) and reported high sensitivity, specificity and negative predictive value for OSNA [2]. As the OSNA assay is essentially an automated procedure, it has clear advantages in standardization, reproducibility and objectivity.…”

“…Intraoperative diagnosis of positive SLN can allow ALND in the same surgical procedure when criteria are present, thus avoiding a second surgery to treat the axilla and decreasing the patient's associated discomfort and institutional costs [2,3].…”

“…Banerjee et al (2014), in a small subgroup of 45 women who had undergone ALND, found that using the CK19 mRNA copy number alone resulted in an AUC of 0.828, which indicates that OSNA is more useful than nomograms in predicting the risk of NSLN metastasis [2].…”

p53 expression in breast cancer predicts tumors with low probability of non‐sentinel nodes infiltration

“…Recently, Banerjee et al . showed that mRNA copy numbers < 1400 were never associated with histologically proven metastasis in NSLN at ALND . It would be interesting to determine whether this cut‐off for mRNA copy numbers varies among different breast cancer subtypes or among tumors showing different molecular features as p53 expression.…”