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

Daniel J Sargent; Qian Shi; Sharlene Gill; Christophe Louvet; Richard B Everson; Udo Kellner; Thomas E Clancy; J Marc Pipas; Murray B Resnick; Michael O Meyers; Tsung-Teh Wu; David Huntsman; Pierre Validire; Umar Farooq; Emily S Pavey; Guillaume Beaudry; Jean-Francois Haince; Yves Fradet

doi:10.1158/1078-0432.CCR-13-2659

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

Journal article

Open access

Peer reviewed

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

Daniel J Sargent, Qian Shi, Sharlene Gill, Christophe Louvet, Richard B Everson, Udo Kellner, Thomas E Clancy, J Marc Pipas, Murray B Resnick, Michael O Meyers, …

Clinical cancer research, Vol.20(16), pp.4361-4369

08/15/2014

DOI: 10.1158/1078-0432.CCR-13-2659

PMID: 24919572

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Abstract

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.

Prognosis

Follow-Up Studies

Humans

Middle Aged

Male

Neoplasm Recurrence, Local - mortality

Neoplasm Recurrence, Local - enzymology

Receptors, Peptide - genetics

Neoplasm Recurrence, Local - pathology

Neoplasm Grading

Aged, 80 and over

Adult

Female

Retrospective Studies

Real-Time Polymerase Chain Reaction

Receptors, Guanylate Cyclase-Coupled - genetics

Colonic Neoplasms - mortality

Neoplasm Invasiveness

RNA, Messenger - genetics

Adenocarcinoma - enzymology

Survival Rate

Lymphatic Metastasis

Receptors, Enterotoxin

Reverse Transcriptase Polymerase Chain Reaction

Adenocarcinoma - secondary

Colonic Neoplasms - pathology

Aged

Biomarkers, Tumor - genetics

Colonic Neoplasms - enzymology

Neoplasm Staging

Adenocarcinoma - mortality

Details

Title: Subtitle: Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study
Creators: Daniel J Sargent - Division of Biomedical Statistics and Informatics; sargent.daniel@mayo.edu
Qian Shi - Division of Biomedical Statistics and Informatics
Sharlene Gill - University of British Columbia, BC Cancer Agency, Vancouver, BC
Christophe Louvet - Oncology and
Richard B Everson - University of Connecticut Health Center, Farmington, Connecticut
Udo Kellner - Johannes Wessling Klinikum Minden, Minden, Germany
Thomas E Clancy - Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts
J Marc Pipas - Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
Murray B Resnick - Alpert Medical School, Brown University and Rhode Island Hospital, Providence, Rhode Island
Michael O Meyers - Division of Surgical Oncology, The University of North Carolina, Chapel Hill, North Carolina
Tsung-Teh Wu - Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota
David Huntsman - University of British Columbia, BC Cancer Agency, Vancouver, BC
Pierre Validire - Pathology, Institut Mutualiste Montsouris, Paris, France; and
Umar Farooq - University of Connecticut Health Center, Farmington, Connecticut
Emily S Pavey - Division of Biomedical Statistics and Informatics
Guillaume Beaudry - DiagnoCure Inc., Québec, Canada; Departments of
Jean-Francois Haince - DiagnoCure Inc., Québec, Canada; Departments of
Yves Fradet - DiagnoCure Inc., Québec, Canada; Departments of
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.20(16), pp.4361-4369
DOI: 10.1158/1078-0432.CCR-13-2659
PMID: 24919572
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Language: English
Date published: 08/15/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Biostatistics; Internal Medicine
Record Identifier: 9984094678402771

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