Abstract
Background
Lymph node (LN) metastasis in colorectal cancer (CRC) is a critical factor in making accurate prognoses and therapeutic decisions. This study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay in accurately diagnosing LN metastases in CRC patients through the specific detection of cytokeratin 19 mRNA levels in LNs.
Methods
The OSNA assay was performed on 121 LNs dissected from early-stage CRC patients (pStage 0 or I) or from patients with benign colorectal disease (study 1). Separately, 385 LNs were dissected from 85 CRC patients (any stage); the OSNA assay was performed on half of each LN, and the results were compared with histopathological examination in 2-mm intervals of the other LN half (study 2).
Results
In study 1, all 121 histopathologically negative LNs were also negative by the OSNA assay (concordance rate for metastasis negative: 1.0, 95% confidence interval [95% CI]: 0.976–1.0). In study 2, the concordance rate between the OSNA assay and the 2-mm-interval histopathological examination was 0.971 (95% CI: 0.950–0.984), with a sensitivity of 0.952 (95% CI: 0.881–0.987) and a specificity of 0.977 (95% CI: 0.953–0.991).
Conclusions
The OSNA assay provided a judgment performance equivalent to a 2-mm-interval histopathological examination, a more detailed assay than the common pathological examination. Therefore, the OSNA assay is considered a new molecular examination method for the diagnosis of LN metastases in CRC patients in clinical settings.
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References
Chapuis PH, Dent OF, Fisher R, Newland RC, Pheils MT, Smyth E, et al. A Multivariate analysis of clinical and pathologic variables in prognosis after resection of large bowel cancer. Br J Surg. 1985;72:698–702.
Moertel CG. Chemotherapy for colorectal cancer. New Engl J Med. 1994;330:1136–42.
Dukes CE, Bussey HJ. The spread of rectal cancer and its effect on prognosis. Br J Cancer. 1958;12:309–20.
Gennari C, Doci R, Rossetti C. Prognostic factors in colorectal cancer. Hepatogastroenterology. 2000;47:310–4.
O’Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with new American Joint Committee on Cancer Sixth edition staging. J Natl Cancer Inst. 2004;96:1420–5.
Burke HB. Outcome prediction and the future of the TNM staging system. J Natl Cancer Inst. 2004;96:1408–9.
Feezor RJ, Copeland EM III, Hochwald SN. Significance of micrometastases in colorectal cancer. Ann Surg Oncol. 2002;9:944–53.
Iddings D, Ahmad A, Elashoff D, Bilchik A. The prognostic effect of micrometastases in previously staged lymph node negative (N0) colorectal carcinoma: a meta-analysis. Ann Surg Oncol. 2006;13:1386–92.
Noura S, Yamamoto H, Ohnishi T, Masuda N, Matsumoto T, Takayama O, et al. Comparative detection of lymph node micrometastases of stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol. 2002;20:4232–41.
Bilchik AJ, Hoon DS, Saha S, Turner RR, Wiese D, DiNome M, et al. Prognostic impact of micrometastases in colon cancer. Ann Surg. 2007;246:568–75.
Tsujimoto M, Nakabayashi K, Yoshidome K, Kaneko T, Iwase T, Akiyama F, et al One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13:4807–16.
Visser M, Jiwa M, Horstman A, Brink AA, Pol RP, van Diest P, et al. Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer. Int J Cancer. 2008;122:2562–7.
Schem C, Maass N, Bauerschlag DO, Carstensen MH, Löning T, Roder C, et al. One-step nucleic acid amplification-a molecular method for the detection of lymph node metastases in breast cancer patients; results of the German study group. Virchows Arch. 2009;454:203–10.
Tamaki Y, Akiyama M, Iwase T, Kaneko T, Tsuda H, Sato K, et al. Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res. 2009;15:2879–84.
Taniyama K, Motoshita J, Sakane J, Makita K, Akai Y, Daito M, et al. Combination analysis of a whole lymph node by one-step nucleic acid amplification and histology for intraoperative detection of micrometastasis. Pathobiology. 2006;73:183–91.
Croner RS, Schellerer V, Demund H, Schildberg C, Papadopulos T, Naschberger E, et al. One step nucleic acid amplification (OSNA) a new method for lymph node staging in colorectal carcinomas. J Transl Med. 2010;8:83.
Zippelius A, Pantel K. RT-PCR-based detection of occult disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. An overview. Ann N Y Acad Sci. 2000;906:110–23.
Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.
Van Cutsem E, Oliveira J. Colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up. Ann Oncol. 2008;19:ii29–30.
Acknowledgment
We thank the staff of the clinical and pathologic laboratories at the participating institutes and the Sysmex Corporation (Reiko Watanabe, Hayato Niiro) for technical support. Grant support: Sysmex Corporation. Note: Sysmex Corporation contributed to providing the RD-100i system, funding of laboratory consumables for the OSNA assay, sample collection, and data analysis, but had no role in data interpretation or writing of this report.
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Yamamoto, H., Sekimoto, M., Oya, M. et al. 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, 1891–1898 (2011). https://doi.org/10.1245/s10434-010-1539-5
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DOI: https://doi.org/10.1245/s10434-010-1539-5