A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes

Sheldon M. Feldman, Savitri Krishnamurthy, William Gillanders, Mark Gittleman, Peter D. Beitsch, Peter R. Young, Christian J. Streck, Pat W. Whitworth, Edward A. Levine, Susan Boolbol, Linda K. Han, Robert Hermann, Dave S.B. Hoon, Armando E. Giuliano, Funda Meric-Bernstam

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2599-2607
Number of pages9
JournalCancer
Volume117
Issue number12
DOIs
StatePublished - Jun 15 2011
Externally publishedYes

Fingerprint

Nucleic Acids
Breast Neoplasms
Cell Biology
Confidence Intervals
Neoplasm Micrometastasis
Pathology
Keratin-19
Lobular Carcinoma
Sensitivity and Specificity
Automation
Hematoxylin
Eosine Yellowish-(YS)
Sentinel Lymph Node
Multicenter Studies
Carcinoma
Messenger RNA
Neoplasms

Keywords

  • breast
  • carcinoma
  • lymph nodes
  • nucleic acid amplification
  • OSNA
  • sentinel

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Feldman, S. M., Krishnamurthy, S., Gillanders, W., Gittleman, M., Beitsch, P. D., Young, P. R., ... Meric-Bernstam, F. (2011). A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. Cancer, 117(12), 2599-2607. https://doi.org/10.1002/cncr.25822

A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. / Feldman, Sheldon M.; Krishnamurthy, Savitri; Gillanders, William; Gittleman, Mark; Beitsch, Peter D.; Young, Peter R.; Streck, Christian J.; Whitworth, Pat W.; Levine, Edward A.; Boolbol, Susan; Han, Linda K.; Hermann, Robert; Hoon, Dave S.B.; Giuliano, Armando E.; Meric-Bernstam, Funda.

In: Cancer, Vol. 117, No. 12, 15.06.2011, p. 2599-2607.

Research output: Contribution to journalArticle

Feldman, SM, Krishnamurthy, S, Gillanders, W, Gittleman, M, Beitsch, PD, Young, PR, Streck, CJ, Whitworth, PW, Levine, EA, Boolbol, S, Han, LK, Hermann, R, Hoon, DSB, Giuliano, AE & Meric-Bernstam, F 2011, 'A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes', Cancer, vol. 117, no. 12, pp. 2599-2607. https://doi.org/10.1002/cncr.25822
Feldman SM, Krishnamurthy S, Gillanders W, Gittleman M, Beitsch PD, Young PR et al. A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. Cancer. 2011 Jun 15;117(12):2599-2607. https://doi.org/10.1002/cncr.25822
Feldman, Sheldon M. ; Krishnamurthy, Savitri ; Gillanders, William ; Gittleman, Mark ; Beitsch, Peter D. ; Young, Peter R. ; Streck, Christian J. ; Whitworth, Pat W. ; Levine, Edward A. ; Boolbol, Susan ; Han, Linda K. ; Hermann, Robert ; Hoon, Dave S.B. ; Giuliano, Armando E. ; Meric-Bernstam, Funda. / A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes. In: Cancer. 2011 ; Vol. 117, No. 12. pp. 2599-2607.
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abstract = "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.",
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T1 - A novel automated assay for the rapid identification of metastatic breast carcinoma in sentinel lymph nodes

AU - Feldman, Sheldon M.

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

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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.

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