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Guanylyl Cyclase C (GC-C)

A Potential Biomarker for Barrett's Esophagus (BE)


Mitroo, Pradnya, M.D.; Bombonati, Alessandro, M.D.; Loren, David, M.D.; Walters, Rhonda; Palazzo, Juan, M.D.; Schulz, Stephanie, Ph.D.; Waldman, Scott, M.D.

American Journal of Gastroenterology: September 2005 - Volume 100 - Issue - p S40
Supplement Abstracts Submitted for the 70th Annual Scientific Meeting of the American College of Gastroenterology: ESOPHAGUS

Department of Gastroenterology, Thomas Jefferson University Hospital, Philadelphia, PA; Department of Pharmacology, Thomas Jefferson University Hospital, Philadelphia, PA and Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA.

Purpose: BE is a premalignant condition that predisposes patients to esophageal adenocarcinoma (AC). Studies have demonstrated that accuracy of presumptive endoscopic or histological suspicion of BE was low at follow-up. Thus, there is a need for prognostic biomarkers that can identify patients at risk for developing BE and, ultimately, AC. GC-C is a receptor selectively expressed in apical membranes of epithelial cells from the duodenum to the rectum, but not by normal esophageal or gastric mucosae in humans. Recent studies revealed that GC-C is an immunohistochemical marker of intestinal metaplasia (IM), dysplasia and AC in the upper GI tract.

The purpose of the study was to evaluate the expression of GC-C protein along the continuum of neoplastic transformation in the esophagus, from IM through AC, by immunohistochemistry (IHC).

Methods: 26 biopsies with BE, 15 with low grade dysplasia (LGD), 6 with high grade dysplasia (HGD) and 3 with AC arising in BE were evaluated. 6 biopsies of normal gastroesophageal junction (GEJ) and 6 of cardiac-type mucosa (CTM) without IM also were evaluated. Paraffin-embedded specimens were stained for GC-C employing purified IgG from rabbits immunized with a peptide derived from human GC-C. Epithelial cells exhibiting apical membrane staining were considered positive for GC-C expression.

Results: GC-C was expressed in 26/26 (100%) cases of BE, 15/15(100%) cases of LGD, 4/6 (67%) cases of HGD and 1/3 (33%) cases of AC. In contrast, 6 normal GEJ and 6 CTM did not stain. Normal squamous epithelia were negative in all cases.

Conclusions: GC-C IHC is 100% sensitive for BE and LGD, since it was consistently expressed in all areas of IM and LGD. Similarly, GC-C IHC is 100% specific for BE and LGD, staining was absent in normal GEJ, CTM, and normal squamous epithelia. As tissues progressed along the continuum of neoplastic transformation to HGD and AC, the detection of GC-C declined, suggesting that the expression of this marker may be down-regulated in later stages of tumorigenesis. Future studies will continue to define the utility of GC-C as a prognostic marker for the initiation of neoplastic transformation (BE), and as a diagnostic marker for the progression of tumorigenesis (LGD, HGD, AC) in the upper GI tract.

© The American College of Gastroenterology 2005. All Rights Reserved.