Ectopic Expression of Guanylyl Cyclase C in Adenocarcinomas of the Esophagus and Stomach

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 11; no. 8; pp. 739 - 744
• Main Authors: PARK, Jason, SCHULZ, Stephanie, HAAF, Janis, KAIRYS, John C, WALDMAN, Scott A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-08-2002
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - analysis; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Guanylate Cyclase - biosynthesis; Guanylate Cyclase - genetics; Humans; Lymphatic Metastasis; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Polymerase Chain Reaction; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide - biosynthesis; Receptors, Peptide - genetics; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Sensitivity and Specificity; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Adenocarcinoma; Human; Stomach; Enzyme; Esophageal disease; Phosphorus-oxygen lyases; Lyases; Malignant tumor; Gene expression; Guanylate cyclase; Esophagus; Membrane receptor; Digestive diseases; Genetics; Advanced stage; Ectopia; Gastric disease; Biological receptor
• ISSN: 1055-9965; 1538-7755

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.