• Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, and David S Weinberg.
• Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 S 10th St, Philadelphia, PA 19107, USA. Scott.Waldman@jefferson.edu
• JAMA. 2009 Feb 18; 301 (7): 745752745-52.

ContextThe 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.ObjectiveTo 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 ParticipantsProspective 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 MeasuresTime to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes.ResultsThirty-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).ConclusionExpression 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.

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