This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Noura, S. Articles by Monden, M. Search for Related Content PubMed PubMed Citation Articles by Noura, S. Articles by Monden, M.

Comparative Detection of Lymph Node Micrometastases of Stage II Colorectal Cancer by Reverse Transcriptase Polymerase Chain Reaction and Immunohistochemistry

From the Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University; and Department of Pathology, School of Allied Health Science, Faculty of Medicine, Osaka University, Osaka, Japan.

Address reprint requests to Hirofumi Yamamoto, MD, PhD, Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita City, Osaka 565-0871, Japan; email: kobunyam{at}surg2.med.osaka-u.ac.jp

PURPOSE: Inconsistent conclusions have been drawn about the clinical significance of micrometastases in lymph nodes (LNs) of node-negative colorectal cancer (CRC) patients. We performed a comparative study of detection of micrometastases using immunohistochemistry (IHC) by anti-cytokeratin antibody and carcinoembryonic antigen (CEA)-specific reverse-transcriptase polymerase chain reaction (RT-PCR) in the same patients, in an attempt to move closer to their clinical application.

PATIENTS AND METHODS: Sixty-four CRC patients, with RNA of good quality available from paraffin-embedded LN specimens, were selected from 84 stage II patients who underwent curative surgery between 1988 and 1996. We investigated associations between the presence of micrometastases by each method and prognosis.

RESULTS: Micrometastases were detected in 19 (29.6%) of 64 patients by RT-PCR and in 35 (54.7%) of 64 patients by IHC. By RT-PCR analysis, patients exhibiting a positive band for CEA mRNA had a significantly worse prognosis than those who were RT-PCR–negative, with respect to both disease-free and overall survival (P = .027 and .015, respectively). By IHC analysis, the presence of micrometastasis did not predict patient outcome in terms of either disease-free or overall survival. Infiltrating pattern of tumor growth characteristic was significantly associated with shorter disease-free survival among various clinical or pathologic factors. By multivariate Cox regression analysis, micrometastasis detected by RT-PCR and the Crohn’s-like lymphoid reaction were both independent prognostic factors.

CONCLUSION: Micrometastases detected by RT-PCR, but not IHC, may be of clinical value in identifying patients who may be at high risk for recurrence of CRC and who are therefore likely to benefit from systemic adjuvant therapy.

The first two authors contributed equally to this study.

This article has been cited by other articles:

				Y. Jiang, G. Casey, I. C. Lavery, Y. Zhang, D. Talantov, M. Martin-McGreevy, M. Skacel, E. Manilich, A. Mazumder, D. Atkins, et al. Development of a Clinically Feasible Molecular Assay to Predict Recurrence of Stage II Colon Cancer J. Mol. Diagn., July 1, 2008; 10(4): 346 - 354. [Abstract] [Full Text] [PDF]

				R. R. Turner, C. Li, and C. C. Compton Newer Pathologic Assessment Techniques for Colorectal Carcinoma Clin. Cancer Res., November 15, 2007; 13(22): 6871s - 6876s. [Abstract] [Full Text] [PDF]

				D. G. Nicastri, J. T. Doucette, T. E. Godfrey, and S. J. Hughes Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?: A Review of the Relevant Literature J. Mol. Diagn., November 1, 2007; 9(5): 563 - 571. [Abstract] [Full Text] [PDF]

				T. Tsujino, I. Seshimo, H. Yamamoto, C. Y. Ngan, K. Ezumi, I. Takemasa, M. Ikeda, M. Sekimoto, N. Matsuura, and M. Monden Stromal Myofibroblasts Predict Disease Recurrence for Colorectal Cancer Clin. Cancer Res., April 1, 2007; 13(7): 2082 - 2090. [Abstract] [Full Text] [PDF]

				D. Iddings, A. Ahmad, D. Elashoff, and A. Bilchik The Prognostic Effect of Micrometastases in Previously Staged Lymph Node Negative (N0) Colorectal Carcinoma: A Meta-analysis Ann. Surg. Oncol., November 1, 2006; 13(11): 1386 - 1392. [Abstract] [Full Text] [PDF]

				M. Pocard, M. Van den Eynde, D. Goere, V. Boige, and D. Malka Sentinel Lymph Node Sampling and Analysis in Colon Cancer: What Is the Question? J. Clin. Oncol., August 1, 2006; 24(22): 3712 - 3713. [Full Text] [PDF]

				Y. Seki, H. Yamamoto, C. Yee Ngan, M. Yasui, N. Tomita, K. Kitani, I. Takemasa, M. Ikeda, M. Sekimoto, N. Matsuura, et al. Construction of a novel DNA decoy that inhibits the oncogenic {beta}-catenin/T-cell factor pathway. Mol. Cancer Ther., April 1, 2006; 5(4): 985 - 994. [Abstract] [Full Text] [PDF]

				L. Xi, W. Gooding, K. McCarty, T. E. Godfrey, and S. J. Hughes Identification of mRNA markers for molecular staging of lymph nodes in colorectal cancer. Clin. Chem., March 1, 2006; 52(3): 520 - 523. [Abstract] [Full Text] [PDF]

				K. Ohrling, D. Edler, M. Hallstrom, P. Ragnhammar, and H. Blomgren Detection of Thymidylate Synthase Expression in Lymph Node Metastases of Colorectal Cancer Can Improve the Prognostic Information J. Clin. Oncol., August 20, 2005; 23(24): 5628 - 5634. [Abstract] [Full Text] [PDF]

				S. B. Ho, A. Hyslop, R. Albrecht, A. Jacobson, M. Spencer, D. A. Rothenberger, G. A. Niehans, J. D'Cunha, and R. A. Kratzke Quantification of Colorectal Cancer Micrometastases in Lymph Nodes by Nested and Real-Time Reverse Transcriptase-PCR Analysis for Carcinoembryonic Antigen Clin. Cancer Res., September 1, 2004; 10(17): 5777 - 5784. [Abstract] [Full Text] [PDF]

				Y. Wang, T. Jatkoe, Y. Zhang, M. G. Mutch, D. Talantov, J. Jiang, H. L. McLeod, and D. Atkins Gene Expression Profiles and Molecular Markers To Predict Recurrence of Dukes' B Colon Cancer J. Clin. Oncol., May 1, 2004; 22(9): 1564 - 1571. [Abstract] [Full Text] [PDF]

				F. S. Doekhie, K. C. M. J. Peeters, R. A. E. M. Tollenaar, and C. J. H. van de Velde Minimal Residual Disease Assessment in Sentinel Nodes of Breast and Gastrointestinal Cancer: A Plea for Standardization Ann. Surg. Oncol., March 1, 2004; 11(3_suppl): 236S - 241S. [Abstract] [Full Text] [PDF]

				T. Mori, Y. Fujiwara, Y. Sugita, T. Azama, T. Ishii, K. Taniguchi, K. Yamazaki, S. Takiguchi, T. Yasuda, M. Yano, et al. Application of Molecular Diagnosis for Detection of Peritoneal Micrometastasis and Evaluation of Preoperative Chemotherapy in Advanced Gastric Carcinoma Ann. Surg. Oncol., January 1, 2004; 11(1): 14 - 20. [Abstract] [Full Text] [PDF]

				C. T. Kuo, D. S.B. Hoon, H. Takeuchi, R. Turner, H.-J. Wang, D. L. Morton, and B. Taback Prediction of Disease Outcome in Melanoma Patients by Molecular Analysis of Paraffin-Embedded Sentinel Lymph Nodes J. Clin. Oncol., October 1, 2003; 21(19): 3566 - 3572. [Abstract] [Full Text] [PDF]

				S. F. Shariat, M. P. Roudier, G. E. Wilcox, M. W. Kattan, P. T. Scardino, R. L. Vessella, S. Erdamar, C. Nguyen, T. M. Wheeler, and K. M. Slawin Comparison of Immunohistochemistry with Reverse Transcription-PCR for the Detection of Micrometastatic Prostate Cancer in Lymph Nodes Cancer Res., August 1, 2003; 63(15): 4662 - 4670. [Abstract] [Full Text] [PDF]