Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas.

Abstract

Guanylyl cyclase C, a receptor for bacterial diarrheagenic enterotoxins, is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by reverse transcriptase-polymerase chain reaction is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well-differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A tissue microarray was created from 69 archival specimens including 44 poorly differentiated, 15 undifferentiated or medullary, and 10 signet ring cell colorectal carcinomas. Matched normal colonic mucosa was used as a positive control. Immunohistochemical staining for Guanylyl cyclase C and CDX2 was evaluated as positive or negative based on at least a 10% extent of staining. Of the 69 tumor samples, 75%, 47%, and 90% of the poorly differentiated, medullary, and signet ring cell tumors were positive for Guanylyl cyclase C and 75%, 40% and 90% of these subsets were positive for CDX2, respectively. There was excellent correlation between Guanylyl cyclase C and CDX2 expression on a case-per-case basis (P < .0001). There was also a statistically significant difference in the Guanylyl cyclase C staining pattern between medullary carcinomas and poorly differentiated, not otherwise specified (P = .05). Immunopositivity for Guanylyl cyclase C was greater than 95% in a separately stained microarray series of well/moderately differentiated colorectal carcinomas. In conclusion, Guanylyl cyclase C expression is lost in a quarter of poorly differentiated and half of undifferentiated colorectal carcinomas. Therefore, the utility of Guanylyl cyclase C expression as a diagnostic marker for colorectal carcinoma may be questionable in poorly differentiated colorectal neoplasms.

• Authors: Brody Winn, Rosemarie Tavares, Andres Matoso, Lelia Noble, Jacqueline Fanion, Scott A Waldman, Murray B Resnick
• Journal: Human pathology (Hum Pathol) Vol. 41 Issue 1 Pg. 123-8 (Jan 2010) ISSN: 1532-8392 [Electronic] United States
• PMID: 19800103 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers, Tumor
• CDX2 Transcription Factor
• CDX2 protein, human
• Homeodomain Proteins
• Receptors, Peptide
• Guanylate Cyclase
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled

Topics

• Adenocarcinoma (metabolism, pathology)
• Aged
• Biomarkers, Tumor (metabolism)
• CDX2 Transcription Factor
• Carcinoma, Medullary (metabolism, pathology)
• Carcinoma, Signet Ring Cell (metabolism, pathology)
• Colorectal Neoplasms (metabolism, pathology)
• Female
• Guanylate Cyclase (metabolism)
• Homeodomain Proteins (metabolism)
• Humans
• Immunohistochemistry
• Intestinal Mucosa (enzymology)
• Male
• Receptors, Enterotoxin
• Receptors, Guanylate Cyclase-Coupled
• Receptors, Peptide (metabolism)
• Tissue Array Analysis