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

• Published in: Human pathology 2010-01, Vol.41 (1), p.123-128
• Main Authors: Winn, Brody, MD, Tavares, Rosemarie, BSc, Matoso, Andres, MD, Noble, Lelia, Fanion, Jacqueline, MSc, Waldman, Scott A., MD, PhD, Resnick, Murray B., MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Awards & honors; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cancer; Carcinoma; Carcinoma, Medullary - metabolism; Carcinoma, Medullary - pathology; Carcinoma, Signet Ring Cell - metabolism; Carcinoma, Signet Ring Cell - pathology; CDX2; CDX2 Transcription Factor; Colon; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Guanylate Cyclase - metabolism; Guanylyl cyclase C; Homeodomain Proteins - metabolism; Humans; Immunohistochemistry; Intestinal Mucosa - enzymology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical research; Medical sciences; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Poorly differentiated; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tissue Array Analysis; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2009.07.009

Summary 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.