Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer

JAMA. 2009 Feb 18;301(7):745-52. doi: 10.1001/jama.2009.141.


Context: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

Objective: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

Design, setting, and participants: Prospective study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers (7 academic medical centers and 2 community hospitals) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis. Patients were followed up for a median of 24 months (range, 2-63 months) for disease recurrence or death.

Main outcome measures: Time to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes.

Results: Thirty-two patients (12.5%) had lymph nodes negative for GUCY2C (pN0 [mol-]), and all but 2 remained free of disease during follow-up (recurrence rate, 6.3%; 95% confidence interval [CI], 0.8%-20.8%). Conversely, 225 patients (87.5%) had lymph nodes positive for GUCY2C (pN0 [mol+]), and 47 developed recurrent disease (20.9%; 95% CI, 15.8%-26.8%) (P = .006). Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis. Patients who were pN0 (mol+) exhibited earlier time to recurrence (adjusted hazard ratio, 4.66; 95% CI, 1.11-19.57; P = .04) and reduced disease-free survival (adjusted hazard ratio, 3.27; 95% CI, 1.15-9.29; P = .03).

Conclusion: Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / enzymology*
  • Disease-Free Survival
  • Female
  • Guanylate Cyclase / analysis
  • Guanylate Cyclase / genetics
  • Guanylate Cyclase / metabolism*
  • Humans
  • Lymph Nodes / enzymology*
  • Lymphatic Metastasis / diagnosis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Observation
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • RNA, Messenger / analysis
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled
  • Receptors, Peptide / analysis
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptors, Peptide
  • GUCY2C protein, human
  • Guanylate Cyclase
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled