Guanylyl cyclase C messenger RNA is a biomarker for recurrent stage II colorectal cancer

Ann Intern Med. 1999 Dec 7;131(11):805-12. doi: 10.7326/0003-4819-131-11-199912070-00002.


Background: Patients with stage II colorectal cancer and no histologic evidence of lymph node invasion develop recurrent disease, presumably because of undetected micrometastases. Guanylyl cyclase C is expressed by intestinal and colorectal cancer cells but not by extraintestinal tissues or tumors.

Objective: To examine the expression of guanylyl cyclase C messenger RNA (mRNA) in lymph nodes of patients with node-negative colorectal cancer who did and did not have recurrent disease.

Design: Case-control study.

Setting: Tertiary care academic medical center.

Patients: Paraffin-embedded lymph nodes were obtained from 21 patients with histologically confirmed node-negative colorectal cancer who had undergone resection. Controls included 11 patients without disease recurrence 6 or more years after resection, and case-patients included 10 patients whose disease recurred up to 3 years after resection.

Measurements: Sections of paraffin-embedded lymph nodes were obtained from each patient and were pooled, and their RNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR).

Results: Guanylyl cyclase C mRNA was expressed in lymph nodes from all patients with recurrent disease but not in those from patients without recurrent disease (P = 0.004). Nested RT-PCR that used primers for carcinoembryonic antigen, a marker for colorectal cancer, identified carcinoembryonic antigen mRNA in lymph nodes from only 1 of 10 patients with recurrent disease and those from 0 of 11 patients without recurrent disease. The odds ratio for death associated with expression of guanylyl cyclase C mRNA in regional lymph nodes was 15.0 (95% CI, 1.1 to 756.7).

Conclusions: Expression of guanylyl cyclase C mRNA in lymph nodes is associated with recurrence of colorectal cancer in patients with stage II disease. Analysis of guanylyl cyclase mRNA expression by RT-PCR may be useful for colorectal cancer staging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Carcinoembryonic Antigen / analysis
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology
  • Female
  • Guanylate Cyclase / analysis*
  • Guanylate Cyclase / genetics
  • Humans
  • Lymph Nodes / enzymology*
  • Lymphatic Metastasis / diagnosis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • RNA, Messenger / analysis*
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled
  • Receptors, Peptide / analysis*
  • Receptors, Peptide / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • Carcinoembryonic Antigen
  • RNA, Messenger
  • Receptors, Peptide
  • Guanylate Cyclase
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled