Breast Cancer

, Volume 21, Issue 5, pp 583–589 | Cite as

GeneSearch™ BLN Assay could replace frozen section and touch imprint cytology for intra-operative assessment of breast sentinel lymph nodes

  • Yong-sheng WangEmail author
  • Yan-hui Liu
  • Tao Ou-yang
  • Xin-hua Yang
  • Jiong Wu
  • Feng-xi Su
  • Xiao Sun
  • Wei-xia Zhong
  • Ning Liao
  • Wen-tao Yang
Original Article



Breast cancer sentinel lymph node (SLN) biopsy has become a common procedure. The GeneSearch™ Breast Lymph Node Assay is a real-time reverse-transcriptase polymerase chain reaction assay for detecting nodal metastases larger than 0.2 mm. The trial is a prospective multi-center clinical trial conducted to validate the assay in China.


Four hundred and seventy-nine consecutive prospective patients were enrolled from six centers. SLNs were sectioned along the short axis into multiple blocks. Odd blocks were tested by the assay intra-operatively, and even blocks were assessed by post-operative histology. Six 4- to 6-μm-thick sections were taken every 150 μm per block. In addition, intra-operative histological assessments were performed on the even blocks of 214 patients by frozen section (FS) and all blocks of 156 patients by touch imprint cytology (TIC).


A total of 1046 SLNs were excised. Overall performance of the assay compared to post-operative histology was accuracy of 91.4 %, sensitivity of 87.5 %, and specificity of 92.9 %. There were no significant differences in assay performance of each center. After a learning curve of about 10 cases, the assay could be performed in a median time of about 35 min. The sensitivity of the assay was similar to the FS (84.9 %, P = 0.885) and was significantly higher than the TIC (70.0 %, P = 0.007) while the specificity of all were comparable.


The GeneSearch™ Breast Lymph Node Assay is an accurate and rapid intra-operative assay for breast SLNs and it can replace FS and TIC for application.


Sentinel lymph node biopsy Breast neoplasms Intraoperative period Polymerase chain reaction Histological evaluation 



This study was supported by Johnson & Johnson Medical, China. Medical writing assistance was also provided by Johnson & Johnson medical, China.

Conflict of interest

The authors have no conflict of interest in the study.


  1. 1.
    Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst. 1999;91:368–73.PubMedCrossRefGoogle Scholar
  2. 2.
    Posther KE, Wilke LG, Giuliano AE. Sentinel lymph node dissection and the current status of American trials on breast lymphatic mapping. Semin Oncol. 2004;31:426–36.PubMedCrossRefGoogle Scholar
  3. 3.
    Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early stage breast cancer. J Clin Oncol. 2005;23:7703–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Silverstein MJ, Recht A, Lagios MD, Bleiweiss IJ, Blumencranz PW, Gizienski T, et al. Special report: consensus conference III. Image-detected breast cancer: state-of-the-art diagnosis and treatment. J Am Coll Surg. 2009;9:504–20.CrossRefGoogle Scholar
  5. 5.
    Langer I, Guller U, Berclaz G, Koechli OR, Moch H, Schaer G, et al. Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study. Breast Cancer Res Treat. 2009;113:129–36.PubMedCrossRefGoogle Scholar
  6. 6.
    Tew K, Irwig L, Matthews A, Crowe P, Macaskill P. Meta-analysis of sentinel node imprint cytology in breast cancer. Br J Surg. 2005;92:1068–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, et al. AJCC cancer staging manual. 6th ed. New York: Springer; 2002.CrossRefGoogle Scholar
  8. 8.
    Julian TB, Blumencranz P, Deck K, Whitworth P, Berry DA, Berry SM, et al. Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer. J Clin Oncol. 2008;26:3338–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20:1319–29.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    de Boer M, van Deurzen CH, van Dijck JA, Borm GF, van Diest PJ, Adang EM, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med. 2009;361:653–63.PubMedCrossRefGoogle Scholar
  11. 11.
    Tjan-Heijnen VC, Pepels MJ, de Boer M, Borm GF, van Dijck JA, van Deurzen CH, et al. Impact of omission of completion axillary lymph node dissection (cALND) or axillary radiotherapy (ax RT) in breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0[i+] in the sentinel lymph node (SN): results from the MIRROR study. 2009 ASCO. Abstract CRA596.Google Scholar
  12. 12.
    Cote R, Giuliano AE, Hawes D, Ballman KV, Whitworth PW, Blumencranz PW, et al. A multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer. 2011 ASCO. Abstract CRA504.Google Scholar
  13. 13.
    Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis. JAMA. 2011;305:569–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    van de Vrande S, Meijer J, Rijnders A, Klinkenbijl JH. The value of intraoperative frozen section examination of sentinel lymph nodes in breast cancer. Eur J Surg Oncol. 2009;35:276–80.PubMedCrossRefGoogle Scholar
  16. 16.
    Chicken DW, Kocjan G, Falzon M, Lee AC, Douek M, Sainsbury R, Keshtgar MR, et al. Intraoperative touch imprint cytology for the diagnosis of sentinel lymph node metastases in breast cancer. Br J Surg. 2006;93:573–6.Google Scholar
  17. 17.
    Zehentner BK, Carter D. Mammaglobin: a candidate diagnostic marker for breast cancer. Clin Biochem. 2004;37:249–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Ishida M, Kitamura K, Kinoshita J, Sasaki M, Kuwahara H, Sugimachi K. Detection of micrometastasis in the sentinel lymph nodes in breast cancer. Surgery. 2002;131:211–6.CrossRefGoogle Scholar
  19. 19.
    Blumencranz P, Whitworth PW, Deck K, Rosenberg A, Reintgen D, Beitsch P, et al. Scientific Impact Recognition Award. Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors. Am J Surg. 2007;194:426–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Viale G, Dell’Orto P, Biasi MO, Stufano V, De Brito Lima LN, et al. Comparative evaluation of an extensive histopathologic examination and a real-time reverse-transcription-polymerase chain reaction assay for mammaglobin and cytokeratin 19 on axillary sentinel lymph nodes of breast carcinoma patients. Ann Surg. 2008;247:136–42.PubMedCrossRefGoogle Scholar
  21. 21.
    Martin Martinez MD, Veys I, Majjaj S, Lespagnard L, Schobbens JC, Rouas G, et al. Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes. Eur J Surg Oncol. 2009;35:387–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Mansel RE, Goyal A, Douglas-Jones A, Woods V, Goyal S, Monypenny I, et al. Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch™ BLN Assay in the operating room: results of the Cardiff study. Breast Cancer Res Treat. 2009;115:595–600.PubMedCrossRefGoogle Scholar
  23. 23.
    Veys I, Majjaj S, Salgado R, Noterman D, Schobbens JC, Manouach F, et al. Evaluation of the histological size of the sentinel lymph node metastases using RT-PCR assay: a rapid tool to estimate the risk of non-sentinel lymph node invasion in patients with breast cancer. Breast Cancer Res Treat. 2010;124:599–605.PubMedCrossRefGoogle Scholar
  24. 24.
    Funasako Y, Uenosono Y, Hirata M, Arigami T, Yanagita S, Arima H, et al. Utility of the GeneSearch breast lymph node assay for the rapid evaluation of sentinel lymph nodes in breast cancer. Cancer. 2010;116:4450–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Sun X, Liu JJ, Wang YS, Song XR, Zhong WX, Zhou CC, et al. Using intra-operative GeneSearch™ Breast Lymph Node Assay to detect breast cancer metastases in sentinel lymph nodes: results from a single institute in China. Chin Med J (Engl). 2011;124:973–7.Google Scholar
  26. 26.
    Chen JJ, Yang BL, Chen JY, Zhang JX, Li DL, Xu WP, et al. A prospective comparison of molecular assay and touch imprint cytology for intraoperative evaluation of sentinel lymph nodes. Chin Med J (Engl). 2011;124:491–7.Google Scholar
  27. 27.
    Liu YH, Xu FP, Liao N, Li L, Zhang GC, Zhuang HG, et al. Efficacy of intraoperative GeneSearch Breast Lymph Node (BLN) Assay for breast cancer metastasis detection in sentinel lymph node in Chinese patients. Cancer Sci. 2010;101:1920–4.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2013

Authors and Affiliations

  • Yong-sheng Wang
    • 1
    Email author
  • Yan-hui Liu
    • 2
  • Tao Ou-yang
    • 3
  • Xin-hua Yang
    • 4
  • Jiong Wu
    • 5
  • Feng-xi Su
    • 6
  • Xiao Sun
    • 1
  • Wei-xia Zhong
    • 1
  • Ning Liao
    • 2
  • Wen-tao Yang
    • 5
  1. 1.Breast Cancer CenterShandong Cancer HospitalJinanPeople’s Republic of China
  2. 2.Breast CenterGuangdong General HospitalGuangzhouPeople’s Republic of China
  3. 3.Breast CenterBeijing Cancer HospitalBeijingPeople’s Republic of China
  4. 4.Breast CenterSouthwest HospitalChongqingPeople’s Republic of China
  5. 5.Department of Breast SurgeryShanghai Cancer HospitalShanghaiPeople’s Republic of China
  6. 6.Department of Breast SurgeryThe Second Affiliated Hospital of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China

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