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Clin Cancer Res. 2014 Aug 15;20(16):4361-9. doi: 10.1158/1078-0432.CCR-13-2659. Epub 2014 Jun 11.

Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study.

Author information

  • 1Division of Biomedical Statistics and Informatics; sargent.daniel@mayo.edu.
  • 2Division of Biomedical Statistics and Informatics;
  • 3University of British Columbia, BC Cancer Agency, Vancouver, BC;
  • 4Oncology and.
  • 5University of Connecticut Health Center, Farmington, Connecticut;
  • 6Johannes Wessling Klinikum Minden, Minden, Germany.
  • 7Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts;
  • 8Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;
  • 9Alpert Medical School, Brown University and Rhode Island Hospital, Providence, Rhode Island;
  • 10Division of Surgical Oncology, The University of North Carolina, Chapel Hill, North Carolina;
  • 11Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota;
  • 12Pathology, Institut Mutualiste Montsouris, Paris, France; and.
  • 13DiagnoCure Inc., Québec, Canada; Departments of.



Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence.


The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n = 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified.


Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) = 2.46, 95% confidence interval (CI), 1.07-5.69, P = 0.035], whereas binary GCC LNR risk class (HR = 1.87, 95% CI, 0.99-3.54, P = 0.054) and mismatch repair (MMR) status (HR = 0.77, 95% CI, 0.36-1.62, P = 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR ≤ 0.20), and low (LNR ≤ 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR = 2.53, 95% CI, 1.24-5.17, P = 0.011).


GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique.

©2014 American Association for Cancer Research.

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