Is Cytomegalovirus Associated With Human Colorectal
Despite the rapid advance in the understanding of molecular pathways underlying human colorectal tumorigenesis, the causes that initiate dysregulation of the pathways remain largely unknown. Human cytomegalovirus (CMV) has been implicated as a potential etiopathogenetic agent. To further investigate whether CMV participates in human colorectal tumorigenesis, we examined 23 colorectal hyperplastic polyps, 65 colorectal adenomas, and 51 colorectal adenocarcinomas by immunohistochemical analysis using 2 antibody mixtures that recognize CMV immediate early, early, and delayed gene products. The results show that while typical nuclear staining (with or without cytoplasmic positivity) was observed in control cases of CMV colitis, no nuclear positivity was detected in any cases studied. Focal and weak cytoplasmic staining was noted in a subset of cases, particularly when a higher antibody concentration was used. This staining was believed to be nonspecific, however, because it also was observed in normal-appearing colonic mucosa. In addition, polymerase chain reaction failed to detect the presence of CMV DNA in 24 selected cases showing nonspecific cytoplasmic immunostaining. These observations demonstrate an absence of CMV proteins and DNA in human colorectal adenocarcinomas and their precursor lesions.
Colorectal adenocarcinoma is the third most common cancer in men and women and is the second leading cause of cancer death in the United States. Harkins et al recently detected cytomegalovirus (CMV) nucleic acids and proteins in a high proportion of human colorectal tumors but not in nonneoplastic colonic mucosa. These findings raise the question of whether persistent CMV infection can induce oncogenic pathways that eventuate in colorectal adenocarcinoma.
Detection of an infectious agent in human cancers might have important implications in cancer treatment and prevention. To further study whether CMV participates in human colorectal tumorigenesis, we examined colorectal hyperplastic polyps, adenomas, adenocarcinomas, and normal-appearing colonic mucosa for the presence of CMV proteins and DNA.