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Frick GS , Pitari GM , Weinberg DS , Hyslop T , Schulz S , Waldman SA
Guanylyl cyclase C: A molecular marker for staging and postoperative surveillance of patients with colorectal cancer
Expert Review of Molecular Diagnostics. 2005 ;5(5) :701-713
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Abstract
Staging patients with colorectal cancer defines their prognosis and therapeutic management. Unfortunately, histopathology, the current standard for staging, is relatively insensitive for detecting occult micrometastases and a significant fraction of patients are understaged and, consequently, undertreated. Similarly, current approaches to postoperative surveillance of patients with colorectal cancer detect disease recurrence at a point when interventions have little impact on survival. The detection of rare cells in tissue, for accurately staging patients, and in blood, for detecting disease recurrence, could be facilitated by employing sensitive and specific markers of disease. Guanylyl cyclase C (GCC), the receptor for the diarrheagenic bacterial heat-stable enterotoxin, is expressed selectively by cells derived from intestinal mucosa, including normal intestinal cells and colorectal tumor cells, but not by extragastrointestinal tissues and tumors. The nearly uniform expression of relatively high levels by metastatic colorectal tumors suggests that GCC may be a sensitive and specific molecular marker for metastatic colorectal cancer cells. Employing GCC reverse transcriptase PCR, occult colorectal cancer micrometastases were detected in lymph nodes that escaped detection by histopathology. Moreover, marker expression correlated with the risk of disease recurrence. Similarly, GCC reverse transcriptase PCR revealed the presence of tumor cells in blood of all patients examined with metastatic colorectal cancer and, in some studies, was associated with an increased risk of disease recurrence and mortality. These observations suggest that GCC reverse transcriptase PCR is a sensitive and specific technique for identifying tumor cells in extraintestinal sites and may be useful for staging and postoperative surveillance of patients with colorectal cancer.
Notes
14737159 (ISSN) Cited By: 0; Export Date: 25 May 2006; Source: Scopus CODEN: ERMDC Language of Original Document: English Correspondence Address: Thomas Jefferson University; Division of Clinical Pharmacology; 132 South 10th Street, United States; email: scott.waldman@jefferson.eu References: Ferlay, J., Bray, F., Pisani, P., Parkin, D.M., (2004) Globoscan 2002: Cancer Incidence, Mortality and Prevalence Worldwide. Second Edition, IARC Press, Lyon, France; Jemal, A., Tiwari, R.C., Murray, T., Cancer statistics, 2004 (2004) CA Cancer J. Clin., 54, pp. 8-29; Gelmann, A., Desnoyers, R., Cagir, B., Weinberg, D., Boman, B.M., Waldman, S.A., Colorectal cancer staging and adjuvant chemotherapy (2000) Expert Opin. Pharmacother., 1, pp. 737-755; Weinberg, D.S., Desnoyers, R., Gelmann, A., Boman, B.M., Waldman, S.A., Postoperative management of local colorectal cancer: Therapy and surveillance (2000) Semin. Gastrointest. 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