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

Abstract

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.

• Authors: Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg
• Journal: JAMA (JAMA) Vol. 301 Issue 7 Pg. 745-52 (Feb 18 2009) ISSN: 1538-3598 [Electronic] United States
• PMID: 19224751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Aged
• Biomarkers, Tumor (analysis, metabolism)
• Colorectal Neoplasms (enzymology)
• Disease-Free Survival
• Female
• Guanylate Cyclase (analysis, genetics, 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, genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction