Guanylyl Cyclase C Messenger RNA Is a Biomarker for Recurrent Stage II Colorectal Cancer

7 December 1999 | Volume 131 Issue 11 | Pages 805-812

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.

Author and Article Information

Grant Support: By grants from the National Institutes of Health (CA75123, CA79663) and Targeted Diagnostics and Therapeutics, Inc. Dr. Gelmann and Mr. Park were supported by training grants from the National Institutes of Health (5T32 GM08562 and T32 DK07705, respectively). Dr. Waldman is the Samuel M.V. Hamilton Professor of Medicine at Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.

Requests for Reprints: Scott A. Waldman, MD, PhD, Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, 132 South 10th Street, 1170 Main, Philadelphia, PA 19107; e-mail, scott.waldman{at}mail.tju.edu. For reprint orders in quantities exceeding 100, please contact the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

Current Author Addresses: Drs. Cagir, Bittner, and Fry: Division of Colorectal Surgery, Department of Surgery, Thomas Jefferson University, 1100 Walnut Street, Philadelphia, PA 19107.

Dr. Gelmann, Mr. Park, Ms. Fava, Mr. Tankelevitch, and Dr. Waldman: Division of Clinical Pharmacology, Department of Medicine, Thomas Jefferson University, 132 South 10th Street, 1170 Main, Philadelphia, PA 19107.

Drs. Weaver and Palazzo: Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 132 South 10th Street, 285 Main, Philadelphia, PA 19107.

Dr. Weinberg: Division of Gastroenterology, Department of Medicine, Thomas Jefferson University, 132 South 10th Street, 480 Main, Philadelphia, PA 19107.