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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Is cytomegalovirus associated with human colorectal tumorigenesis?
Olaronke Akintola-Ogunremi1, Qing Luo, Tong-Chuan He
1Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Abstract:
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.
Insights
Human cytomegalovirus (CMV) does not appear to cause colorectal cancer. Studies found no evidence of CMV proteins or DNA in colorectal tumors or precancerous lesions, refuting its role in colorectal tumorigenesis.
Area of Science:
- Gastroenterology
- Oncology
- Virology
Background:
- Colorectal tumorigenesis involves complex molecular pathways, but initiating causes are often unclear.
- Human cytomegalovirus (CMV) has been investigated as a potential factor in colorectal cancer development.
Purpose of the Study:
- To investigate the potential role of human cytomegalovirus (CMV) in the initiation and progression of human colorectal tumorigenesis.
- To determine the presence or absence of CMV proteins and DNA in colorectal adenocarcinomas and their precursor lesions.
Main Methods:
- Immunohistochemical analysis was performed on 23 hyperplastic polyps, 65 adenomas, and 51 adenocarcinomas using antibodies against CMV immediate early, early, and delayed gene products.
- Polymerase chain reaction (PCR) was used to detect CMV DNA in selected cases with non-specific immunostaining.
Main Results:
- No specific nuclear CMV staining was detected in any colorectal tumors or precursor lesions.
- Focal, weak cytoplasmic staining was observed in some cases but was deemed non-specific as it also appeared in normal colonic mucosa.
- CMV DNA was not detected by PCR in selected cases exhibiting non-specific cytoplasmic immunostaining.
Conclusions:
- The study demonstrates the absence of CMV proteins and DNA in human colorectal adenocarcinomas and their precursor lesions.
- These findings do not support the hypothesis that human cytomegalovirus (CMV) plays a role in human colorectal tumorigenesis.
