Guanylyl cyclase C: a molecular marker for staging and postoperative surveillance of patients with colorectal cancer.
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.
Frick
Glen S
GS
Respiratory & Inflammation Centre of Excellence for Drug Discovery, Discovery Medicine, GlaxoSmithKline, PA, USA. glen.s.frick@gsk.com
Pitari
Giovanni M
GM
Weinberg
David S
DS
Hyslop
Terry
T
Schulz
Stephanie
S
Waldman
Scott A
SA
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology* / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D006162:Guanylate Cyclase / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D009367:Neoplasm Staging; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000032:analysis / Q000097:blood / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled