Prospective Multicenter Study of a Novel Fully Automated Molecular Test for Identification of Metastatic Carcinoma in Axillary Sentinel Lymph Nodes in Breast Cancer – The US OSNA Breast Cancer Sentinel Lymph Node Study Group
The US OSNA Breast Cancer Sentinel Lymph Node Study Group. MDACC, Houston
Background: Molecular analysis of lymph nodes is useful for accurate, objective and rapid evaluation of the entire node for metastatic carcinoma. We assessed the performance of a novel, fully automated molecular test, One-step nucleic acid amplification (OSNA) Breast Cancer System, for detection of metastatic carcinoma in axillary sentinel lymph nodes (SLN) in a large prospective trial in comparison to detailed histopathologic(HP) examination.
Design: SLNs from early stage breast cancer patients were sliced (1-mm) using a proprietary 5-blade lymph node cutter. Alternate slices were analyzed using the OSNA system or deatiled HP examination. The OSNA system detects CK19 mRNA and was calibrated to detect tumor deposits >0.2 mm. OSNA results were classified as negative (<250 copies/μl); + as micro (≥250 copies/μl); or ++ as macrometastases (≥5000 copies/μl). The performance of OSNA system was compared with that of HP by calculating overall agreement, sensitivity and specificity using exact binomial 95% confidence intervals.
Results: We studied 1044 SLNs from 496 patients enrolled in 4 academic and 7 community centers. HP examination revealed metastatic carcinoma in 138 SLNs (13%), including 95 macrometastases (69%) and 43 micrometastases (31%). The OSNA system detected 86 (62%) of those macro and 21 (15%) of those micrometastases. The OSNA system also detected 9 macro (6%) and 29 micrometastases (20%) that were negative by HP. The discordance in the results between the two methods was proven to be due to tissue allocation bias and technical factors. Overall, the OSNA system detected metastases in 145 SLNs (14%). Analysis of up to three SLNs was completed in 45 minutes. The overall agreement, sensitivity, and specificity of the OSNA system on a SLN basis when compared to HP was 95.8%, 82.7%, and 97.7%, respectively (after discordant sample analysis (DCA)). After DCA, all OSNA ++ results were deemed to reflect nodal disease. The OSNA system performed well in academic and community hospitals.
Conclusions: 1) The performance of the OSNA Breast Cancer System was comparable with that of conventional HP examination in detecting metastatic carcinoma in SLNs. 2) The assay has features such as full automation, easy to learn and use, semi-quantitative results (+ = micromets and ++ = macromets) and rapid analysis, which makes it suitable for intraoperative and/or permanent comprehensive evaluation of SLNs in any pathology laboratory for routine patient care.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 43, Wednesday Morning