Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach.

Abstract

Guanylyl cyclase C (GC-C), a receptor specifically expressed in cells originating from differentiated intestinal epithelium, is a marker and therapeutic target for colorectal cancer metastases. Intestinal metaplasia, in which epithelial cells assume histological and molecular characteristics of differentiated intestinal enterocytes, is a common precursor to adenocarcinomas of the esophagus and stomach. Thus, those tumors, tissues adjacent to them, and their associated regional lymph nodes were assessed for GC-C expression by reverse transcription coupled with the PCR. GC-C mRNA was detected in five of five and eight of nine esophageal and gastric adenocarcinomas, respectively. Also, GC-C mRNA was detected in three of five and six of seven tissues adjacent to, but not histologically involved in, esophageal and gastric adenocarcinomas, respectively, reflecting molecular changes associated with neoplastic transformation preceding histopathological changes. In contrast, three normal gastric specimens did not express GC-C. Furthermore, GC-C mRNA was detected in 1 of 1 lymph node containing tumor cells by histopathology from a patient with gastric adenocarcinoma and in 3 of 11 lymph nodes, all of which were free of tumor cells by histopathology, from a patient with a gastroesophageal junction tumor. This is the first demonstration that GC-C is ectopically expressed by primary and metastatic adenocarcinomas of the esophagus and stomach and suggests that GC-C may be a sensitive and specific clinical marker and target for adenocarcinomas of the upper gastrointestinal tract.

• Authors: Jason Park, Stephanie Schulz, Janis Haaf, John C Kairys, Scott A Waldman
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 11 Issue 8 Pg. 739-44 (Aug 2002) ISSN: 1055-9965 [Print] United States
• PMID: 12163327 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Adenocarcinoma (genetics, pathology)
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis)
• Esophageal Neoplasms (genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Guanylate Cyclase (biosynthesis, genetics)
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Metastasis
• Polymerase Chain Reaction
• RNA, Messenger (analysis, biosynthesis)
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled
• Receptors, Peptide (biosynthesis, genetics)
• Sensitivity and Specificity
• Stomach Neoplasms (genetics, pathology)