TY - JOUR
T1 - A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes
AU - Feldman, Sheldon
AU - Krishnamurthy, Savitri
AU - Gillanders, William
AU - Gittleman, Mark
AU - Beitsch, Peter D.
AU - Young, Peter R.
AU - Streck, Christian J.
AU - Whitworth, Pat W.
AU - Levine, Edward A.
AU - Boolbol, Susan
AU - Han, Linda K.
AU - Hermann, Robert
AU - Hoon, Dave S.B.
AU - Giuliano, Armando E.
AU - Meric-Bernstam, Funda
PY - 2011/6/15
Y1 - 2011/6/15
N2 - BACKGROUND: The authors prospectively evaluated the performance of a proprietary molecular testing platform using one-step nucleic acid amplification (OSNA) for the detection of metastatic carcinoma in sentinel lymph nodes (SLNs) in a large multicenter trial and compared the OSNA results with the results from a detailed postoperative histopathologic evaluation (reference pathology) and from intraoperative imprint cytology (IC). METHODS: In total, 1044 SLN samples from 496 patients at 11 clinical sites were analyzed. Alternate 1-mm sections were subjected to either detailed histopathologic evaluation with hematoxylin and eosin and pancytokeratin immunostaining or the OSNA Breast Cancer System, which was calibrated to detect tumor deposits >0.2 mm by measuring cytokeratin 19 messenger RNA. At 7 sites, IC was performed before permanent section. The OSNA results were classified as negative (<250 copies/μL), micrometastases (from ≥250 to <5000 copies/μL), or macrometastases (≥5000 copies/μL). RESULTS: The sensitivity and specificity of the OSNA breast cancer system compared with reference pathology were 77.5% (95% confidence interval, 69.7%-84.2%) and 95.8% (95% confidence interval, 94.3%-97.0%), respectively, before discordant case analyses (DCA). Sensitivity and specificity after DCA were 82.7% and 97.7%, and final concordance was 95.8%. Performance for invasive lobular carcinoma demonstrated 88.2% sensitivity (95% confidence interval, 63.6%-98.5%) and 98.5% specificity (95% confidence interval, 92%-100%). The sensitivity of OSNA was significantly better than that of IC (80% vs 63%; P =.0229). CONCLUSIONS: The OSNA breast cancer system proved to be highly accurate for the detection of metastatic breast cancer in axillary SLNs. Sensitivity was comparable to that predicted for conventional postoperative histologic examination at 2-mm intervals and was significantly more sensitive than IC. Automation, semiquantitative results enabling the differentiation of macrometastasis and micrometastasis, and rapid results render the assay suitable for intraoperative and/or permanent evaluation of SLNs.
AB - BACKGROUND: The authors prospectively evaluated the performance of a proprietary molecular testing platform using one-step nucleic acid amplification (OSNA) for the detection of metastatic carcinoma in sentinel lymph nodes (SLNs) in a large multicenter trial and compared the OSNA results with the results from a detailed postoperative histopathologic evaluation (reference pathology) and from intraoperative imprint cytology (IC). METHODS: In total, 1044 SLN samples from 496 patients at 11 clinical sites were analyzed. Alternate 1-mm sections were subjected to either detailed histopathologic evaluation with hematoxylin and eosin and pancytokeratin immunostaining or the OSNA Breast Cancer System, which was calibrated to detect tumor deposits >0.2 mm by measuring cytokeratin 19 messenger RNA. At 7 sites, IC was performed before permanent section. The OSNA results were classified as negative (<250 copies/μL), micrometastases (from ≥250 to <5000 copies/μL), or macrometastases (≥5000 copies/μL). RESULTS: The sensitivity and specificity of the OSNA breast cancer system compared with reference pathology were 77.5% (95% confidence interval, 69.7%-84.2%) and 95.8% (95% confidence interval, 94.3%-97.0%), respectively, before discordant case analyses (DCA). Sensitivity and specificity after DCA were 82.7% and 97.7%, and final concordance was 95.8%. Performance for invasive lobular carcinoma demonstrated 88.2% sensitivity (95% confidence interval, 63.6%-98.5%) and 98.5% specificity (95% confidence interval, 92%-100%). The sensitivity of OSNA was significantly better than that of IC (80% vs 63%; P =.0229). CONCLUSIONS: The OSNA breast cancer system proved to be highly accurate for the detection of metastatic breast cancer in axillary SLNs. Sensitivity was comparable to that predicted for conventional postoperative histologic examination at 2-mm intervals and was significantly more sensitive than IC. Automation, semiquantitative results enabling the differentiation of macrometastasis and micrometastasis, and rapid results render the assay suitable for intraoperative and/or permanent evaluation of SLNs.
KW - OSNA
KW - breast
KW - carcinoma
KW - lymph nodes
KW - nucleic acid amplification
KW - sentinel
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U2 - 10.1002/cncr.25822
DO - 10.1002/cncr.25822
M3 - Article
C2 - 21226034
AN - SCOPUS:79957891662
SN - 0008-543X
VL - 117
SP - 2599
EP - 2607
JO - Cancer
JF - Cancer
IS - 12
ER -
