title: Evaluation of guanylyl cyclase C lymph node status for colon cancer staging and prognosis.
abstract: OBJECTIVE
  The prognostic significance of guanylyl cyclase C (GCC) gene expression in lymph nodes (LNs) was evaluated in patients with stage II colon cancer who were not treated with adjuvant chemotherapy. We report a planned analysis performed on 241 patients.
  
  
  METHODS
  GCC mRNA was quantified by RT-qPCR using formalin-fixed LN tissues from patients with untreated stage II colon cancer who were diagnosed from 1999-2006 with at least ten LNs examined and blinded to clinical outcomes. Lymph node ratio (LNR) is the number of GCC-positive nodes divided by total number of informative LNs. Risk categories of low (0-0.1) and high (>0.1) for LNR were chosen by significance using Cox regression models. The data were tested for association with time to recurrence.
  
  
  RESULTS
  Twenty-nine patients (12%) had a disease recurrence or cancer death. The LNR significantly predicted higher recurrence risk for 84 patients (34.9%) classified as high risk (hazard ratio (HR), 2.38; P=0.02). The estimated 5-year recurrence rates were 10% and 27% for the low- and high-risk groups, respectively. After adjusting for age, T stage, number of nodes assessed, and MMR status, a significant association remained (HR, 2.61; P=0.02). In a subset of patients (n=181) with T3 tumor, ≥12 nodes examined and negative margins, a significant association between the GCC LNR and recurrence risk also was observed (HR, 5.06; P=0.003).
  
  
  CONCLUSIONS
  Our preliminary results suggest that detection of GCC mRNA in LNs is associated with risk of disease recurrence in patients with untreated stage II colon cancer. A larger validation study is ongoing.
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. sargent.daniel@mayo.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Murray B
authors.initials: MB
authors.lastname: Resnick
authors.forename: Michael O
authors.initials: MO
authors.lastname: Meyers
authors.forename: Atoussa
authors.initials: A
authors.lastname: Goldar-Najafi
authors.forename: Thomas
authors.initials: T
authors.lastname: Clancy
authors.forename: Sharlene
authors.initials: S
authors.lastname: Gill
authors.forename: Gary O
authors.initials: GO
authors.lastname: Siemons
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.forename: Brian M
authors.initials: BM
authors.lastname: Bot
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.forename: Guillaume
authors.initials: G
authors.lastname: Beaudry
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Haince
authors.forename: Yves
authors.initials: Y
authors.lastname: Fradet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; 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: D012333:RNA, Messenger; D018000:Receptors, Peptide; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled