Techniques in Coloproctology

, Volume 21, Issue 9, pp 693–699 | Cite as

Is it time for one-step nucleic acid amplification (OSNA) in colorectal cancer? A systematic review and meta-analysis

  • J. B. WildEmail author
  • N. Iqbal
  • J. Francombe
  • T. Papettas
  • D. S. Sanders
  • S. Ramcharan



Lymph node metastasis (LNM) is prognostic in colorectal cancer (CRC). However, evaluation by routine haematoxylin and eosin histology (HE) limits nodal examination and is subjective. Missed LNMs from tissue allocation bias (TAB) might under-stage disease, leading to under-treatment. One-step nucleic acid amplification (OSNA) for CK19 messenger ribonucleic acid (mRNA), a marker of LNM, analyses the whole node. The aim of the present systematic review and meta-analysis was to assess recent studies on OSNA versus HE and its implications for CRC staging and treatment.


Databases including OVID, Medline and Google Scholar were searched for OSNA, LNM and CRC. Study results were pooled using a random-effects model. Summary receiver operator curves (SROC) assessed OSNA’s performance in detecting LNM when compared to routine HE histology.


Five case–control studies analysing 4080 nodes from 622 patients were included. The summary estimates of pooled results for OSNA were sensitivity 0.90 [95% confidence interval (CI) 0.86–0.93], specificity 0.94 (95% CI 0.93–0.95) and diagnostic odds ratio 179.5 (CI 58.35–552.2, p < 0.0001). The SROC curve indicated a maximum joint sensitivity and specificity of 0.88 and area under the curve of 0.94, p < 0.0001. On average, 5.4% HE-negative nodes were upstaged by OSNA.


OSNA is as good as routine HE. It may avoid TAB and offer a more objective and standardised assay of LNM. However, for upstaging, its usefulness as an adjunct to HE or superiority to HE requires further assessment of the benefits, if any, of adjuvant therapy in patients upstaged by OSNA.


Colorectal cancer Lymph node metastasis Prognosis One-step nucleic acid amplification OSNA 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All studies included in this analysis had ethical approval from their appropriate ethical bodies.

Informed consent

Formal consent was not required for this study.


  1. 1.
    Cancer IAfRo (2012) World Cancer Fact Sheet. GLOBOCON. 2013 ed. France: International Agency for Research on Cancer. Accessed Feb 2017
  2. 2.
    UK OfNS (2014) Cancer survival in England: adults diagnosed 2008–2012, followed up to 2013 Office for National Statistics Website: ONS. Accessed Feb 2017
  3. 3.
    Rachet B, Maringe C, Nur U et al (2009) Population-based cancer survival trends in England and Wales up to 2007: an assessment of the NHS cancer plan for England. Lancet Oncol 10(4):351–369. doi: 10.1016/S1470-2045(09)70028-2 CrossRefPubMedGoogle Scholar
  4. 4.
    Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi: 10.1002/ijc.29210 CrossRefPubMedGoogle Scholar
  5. 5.
    Sargent D, Sobrero A, Grothey A et al (2009) Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol 27(6):872–877. doi: 10.1200/JCO.2008.19.5362 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American joint committee on cancer sixth edition staging. J Natl Cancer Inst 96(19):1420–1425. doi: 10.1093/jnci/djh275 CrossRefPubMedGoogle Scholar
  7. 7.
    Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK (2010) Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol 28(2):264–271. doi: 10.1200/JCO.2009.24.0952 CrossRefPubMedGoogle Scholar
  8. 8.
    Yamamoto H, Sekimoto M, Oya M et al (2011) OSNA-based novel molecular testing for lymph node metastases in colorectal cancer patients: results from a multicenter clinical performance study in Japan. Ann Surg Oncol 18(7):1891–1898. doi: 10.1245/s10434-010-1539-5 CrossRefPubMedGoogle Scholar
  9. 9.
    Croner RS, Schellerer V, Demund H et al (2010) One step nucleic acid amplification (OSNA)—a new method for lymph node staging in colorectal carcinomas. J Transl Med 8:83. doi: 10.1186/1479-5876-8-83 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Kennedy RD, Bylesjo M, Kerr P et al (2011) Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol 29(35):4620–4626. doi: 10.1200/JCO.2011.35.4498 CrossRefPubMedGoogle Scholar
  11. 11.
    Pathologists RCo (2014) Standards and datasets for reporting cancers dataset for colorectal cancer histopathology reports: Royal College of Pathologists. (updated July 2014; cited 2014 3rd Edition).–3rd-edition-.html. Accessed Feb 2017
  12. 12.
    Hyslop T, Waldman SA (2013) Molecular staging of node negative patients with colorectal cancer. J Cancer 4(3):193–199. doi: 10.7150/jca.5830 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Resch A, Langner C (2013) Lymph node staging in colorectal cancer: old controversies and recent advances. World J Gastroenterol 19(46):8515–8526. doi: 10.3748/wjg.v19.i46.8515 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bembenek AE, Rosenberg R, Wagler E et al (2007) Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial. Ann Surg 245(6):858–863. doi: 10.1097/01.sla.0000250428.46656.7e CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Guller U, Zettl A, Worni M et al (2012) Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging? Cancer 118(24):6039–6045. doi: 10.1002/cncr.27667 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Tiernan JP, Verghese ET, Nair A et al (2014) Systematic review and meta-analysis of cytokeratin 19-based one-step nucleic acid amplification versus histopathology for sentinel lymph node assessment in breast cancer. Br J Surg 1(4):298–306. doi: 10.1002/bjs.9386 CrossRefGoogle Scholar
  17. 17.
    Yamamoto N, Daito M, Hiyama K et al (2013) An optimal mRNA marker for OSNA (one-step nucleic acid amplification) based lymph node metastasis detection in colorectal cancer patients. Jpn J Clin Oncol 43(3):264–270. doi: 10.1093/jjco/hys227 CrossRefPubMedGoogle Scholar
  18. 18.
    Taniyama K, Motoshita J, Sakane J et al (2006) Combination analysis of a whole lymph node by one-step nucleic acid amplification and histology for intraoperative detection of micrometastasis. Pathobiology 73(4):183–191. doi: 10.1159/000096019 CrossRefPubMedGoogle Scholar
  19. 19.
    Yamamoto H, Tomita N, Inomata M et al (2016) OSNA-assisted molecular staging in colorectal cancer: a prospective multicenter trial in Japan. Ann Surg Oncol 23(2):391–396. doi: 10.1245/s10434-015-4880-x CrossRefPubMedGoogle Scholar
  20. 20.
    Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A (2006) Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 6:31. doi: 10.1186/1471-2288-6-31 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Liefers GJ, Cleton-Jansen AM, van de Velde CJ et al (1998) Micrometastases and survival in stage II colorectal cancer. N Engl J Med 339(4):223–228. doi: 10.1056/NEJM199807233390403 CrossRefPubMedGoogle Scholar
  22. 22.
    Bilchik AJ, Hoon DS, Saha S et al (2007) Prognostic impact of micro metastases in colon cancer: interim results of a prospective multicenter trial. Ann Surg 246(4):568–575. doi: 10.1097/SLA.0b013e318155a9c7 (discussion 75–77) CrossRefPubMedGoogle Scholar
  23. 23.
    Mescoli C, Albertoni L, Pucciarelli S et al (2012) Isolated tumor cells in regional lymph nodes as relapse predictors in stage I and II colorectal cancer. J Clin Oncol 30(9):965–971. doi: 10.1200/JCO.2011.35.9539 CrossRefPubMedGoogle Scholar
  24. 24.
    Aldecoa I, Atares B, Tarragona J et al (2016) Molecularly determined total tumour load in lymph nodes of stage I–II colon cancer patients correlates with high-risk factors. A multicentre prospective study. Virchows Arch 469(4):385–394. doi: 10.1007/s00428-016-1990-1 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Nordgard O, Oltedal S, Korner H et al (2009) Quantitative RT-PCR detection of tumor cells in sentinel lymph nodes isolated from colon cancer patients with an ex vivo approach. Ann Surg 249(4):602–607. doi: 10.1097/SLA.0b013e31819ec923 CrossRefPubMedGoogle Scholar
  26. 26.
    Iddings D, Ahmad A, Elashoff D, Bilchik A (2006) The prognostic effect of micrometastases in previously staged lymph node negative (N0) colorectal carcinoma: a meta-analysis. Ann Surg Oncol 13(11):1386–1392CrossRefPubMedGoogle Scholar
  27. 27.
    Nicastri DG, Doucette JT, Godfrey TE, Hughes SJ (2007) Is occult lymph node disease in colorectal cancer patients clinically significant? A review of the relevant literature. J Mol Diagn 9(5):563–571. doi: 10.2353/jmoldx.2007.070032 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Vogelaar FJ, Reimers MS, van der Linden RL et al (2014) The diagnostic value of one-step nucleic acid amplification (OSNA) for sentinel lymph nodes in colon cancer patients. Ann Surg Oncol 21(12):3924–3930. doi: 10.1245/s10434-014-3820-5 CrossRefPubMedGoogle Scholar
  29. 29.
    Hyslop T, Waldman SA (2013) Guanylyl cyclase C as a biomarker in colorectal cancer. Biomark Med 7(1):159–167. doi: 10.2217/bmm.12.90 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Saha S, Dan AG, Viehl CT, Zuber M, Wiese D (2005) Sentinel lymph node mapping in colon and rectal cancer: its impact on staging, limitations, and pitfalls. Cancer Treat Res 127:105–122CrossRefPubMedGoogle Scholar
  31. 31.
    Wright FC, Law CH, Berry S, Smith AJ (2009) Clinically important aspects of lymph node assessment in colon cancer. J Surg Oncol 99(4):248–255. doi: 10.1002/jso.21226 CrossRefPubMedGoogle Scholar
  32. 32.
    Swanson RS, Compton CC, Stewart AK, Bland KI (2003) The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol 10(1):65–71CrossRefPubMedGoogle Scholar
  33. 33.
    Schaafsma BE, Verbeek FP, van der Vorst JR et al (2013) Ex vivo sentinel node mapping in colon cancer combining blue dye staining and fluorescence imaging. J Surg Res 183(1):253–257. doi: 10.1016/j.jss.2013.01.003 CrossRefPubMedGoogle Scholar
  34. 34.
    NICE (2017) Medtech innovation briefing 77. 24th August 2016. Accessed Feb 2017
  35. 35.
    Fellegara G, Carcangiu ML, Rosai J (2011) Benign epithelial inclusions in axillary lymph nodes: report of 18 cases and review of the literature. Am J Surg Pathol 35(8):1123–1133. doi: 10.1097/PAS.0b013e3182237985 CrossRefPubMedGoogle Scholar
  36. 36.
    Huxley N, Jones-Hughes T, Coelho H, Snowsill T, Cooper C, Meng Y et al (2015) A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer. Health Technol Assess 19(2):5–25. doi: 10.3310/hta19020 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • J. B. Wild
    • 1
    Email author
  • N. Iqbal
    • 1
  • J. Francombe
    • 1
  • T. Papettas
    • 1
  • D. S. Sanders
    • 2
  • S. Ramcharan
    • 1
    • 3
  1. 1.Departments of Colorectal SurgerySouth Warwickshire NHS Foundation TrustWarwickUK
  2. 2.Departments of HistopathologySouth Warwickshire NHS Foundation TrustWarwickUK
  3. 3.Department of Experimental MedicineUniversity of BirminghamBirminghamUK

Personalised recommendations