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

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.