Occult tumor burden predicts disease recurrence in lymph node-negative colorectal cancer.

Abstract

PURPOSE:

Lymph node involvement by histopathology informs colorectal cancer prognosis, whereas recurrence in 25% of node-negative patients suggests the presence of occult metastasis. GUCY2C (guanylyl cyclase C) is a marker of colorectal cancer cells that identifies occult nodal metastases associated with recurrence risk. Here, we defined the association of occult tumor burden, quantified by GUCY2C reverse transcriptase-PCR (RT-PCR), with outcomes in colorectal cancer.

EXPERIMENTAL DESIGN:

Lymph nodes (range: 2-159) from 291 prospectively enrolled node-negative colorectal cancer patients were analyzed by histopathology and GUCY2C quantitative RT-PCR. Participants were followed for a median of 24 months (range: 2-63). Time to recurrence and disease-free survival served as primary and secondary outcomes, respectively. Association of outcomes with prognostic markers, including molecular tumor burden, was estimated by recursive partitioning and Cox models.

RESULTS:

In this cohort, 176 (60%) patients exhibited low tumor burden (Mol(Low)), and all but four remained free of disease [recurrence rate 2.3% (95% CI, 0.1-4.5%)]. Also, 90 (31%) patients exhibited intermediate tumor burden (Mol(Int)) and 30 [33.3% (23.7-44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (Mol(High)) and 17 [68.0% (46.5-85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. Mol(Int) and Mol(High) patients exhibited a graded risk of earlier time to recurrence [Mol(Int), adjusted HR 25.52 (11.08-143.18); P < 0.001; Mol(High), 65.38 (39.01-676.94); P < 0.001] and reduced disease-free survival [Mol(Int), 9.77 (6.26-87.26); P < 0.001; Mol(High), 22.97 (21.59-316.16); P < 0.001].

CONCLUSION:

Molecular tumor burden in lymph nodes is independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.

• Authors: Terry Hyslop, David S Weinberg, Stephanie Schulz, Alan Barkun, Scott A Waldman
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 10 Pg. 3293-303 (May 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21307149 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Validation Study)
• Copyright: ©2011 AACR.

Chemical References

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

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, genetics, metabolism)
• Carcinoma (diagnosis, genetics, pathology)
• Cohort Studies
• Colorectal Neoplasms (diagnosis, genetics, pathology)
• Female
• Follow-Up Studies
• Humans
• Lymph Nodes (metabolism, pathology)
• Lymphatic Metastasis
• Male
• Middle Aged
• Prognosis
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled (analysis, genetics, metabolism)
• Receptors, Peptide (analysis, genetics, metabolism)
• Recurrence
• Tumor Burden