Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas.
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.
Winn
Brody
B
Department of Pathology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903, USA.
Tavares
Rosemarie
R
Matoso
Andres
A
Noble
Lelia
L
Fanion
Jacqueline
J
Waldman
Scott A
SA
Resnick
Murray B
MB
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D018000:Receptors, Peptide; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled