title: Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Biomedical Statistics and Informatics; sargent.daniel@mayo.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.affiliation: Division of Biomedical Statistics and Informatics;
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.affiliation: University of British Columbia, BC Cancer Agency, Vancouver, BC;
authors.forename: Sharlene
authors.initials: S
authors.lastname: Gill
authors.affiliation: Oncology and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut;
authors.forename: Richard B
authors.initials: RB
authors.lastname: Everson
authors.affiliation: Johannes Wessling Klinikum Minden, Minden, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Kellner
authors.affiliation: Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts;
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Clancy
authors.affiliation: Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire;
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
authors.affiliation: Alpert Medical School, Brown University and Rhode Island Hospital, Providence, Rhode Island;
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.affiliation: Division of Surgical Oncology, The University of North Carolina, Chapel Hill, North Carolina;
authors.forename: Michael O
authors.initials: MO
authors.lastname: Meyers
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota;
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.affiliation: University of British Columbia, BC Cancer Agency, Vancouver, BC;
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.affiliation: Pathology, Institut Mutualiste Montsouris, Paris, France; and.
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.affiliation: University of Connecticut Health Center, Farmington, Connecticut;
authors.forename: Umar
authors.initials: U
authors.lastname: Farooq
authors.affiliation: Division of Biomedical Statistics and Informatics;
authors.forename: Emily S
authors.initials: ES
authors.lastname: Pavey
authors.affiliation: DiagnoCure Inc., Québec, Canada; Departments of.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Beaudry
authors.affiliation: DiagnoCure Inc., Québec, Canada; Departments of.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Haince
authors.affiliation: DiagnoCure Inc., Québec, Canada; Departments of.
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018000:Receptors, Peptide; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled