Immunohistochemical Characterization of Large Intestinal Adenocarcinoma in the Rhesus Macaque (Macaca mulatta)

Area of Science:

• Veterinary Pathology
• Comparative Oncology
• Gastrointestinal Disease

Background:

• Spontaneous adenocarcinomas of the ileocecal junction and colon are prevalent in aging rhesus macaques.
• These macaque tumors share gross and histologic similarities with human colorectal cancer.
• Limited knowledge exists on the immunohistochemical protein expression in macaque colorectal tumors relevant to human disease pathogenesis.

Purpose of the Study:

• To retrospectively review rhesus macaque large intestinal carcinomas.
• To evaluate immunohistochemical expression patterns of proteins implicated in human colorectal cancer pathogenesis.
• To assess the potential of rhesus macaques as an animal model for human colorectal cancer.

Main Methods:

• Retrospective review of 22 rhesus macaque large intestinal carcinoma cases.
• Immunohistochemical analysis of protein expression (CD10, β-catenin, sirtuin 1, cytokeratin 17, p53).
• Zymographic analysis of serum matrix metalloproteinases 2 and 9 in 5 cases.

Main Results:

• All macaque adenocarcinomas showed altered expression of at least one evaluated protein compared to controls.
• Histologic features included mucin deposition, transmural spread, and lymphatic invasion.
• No significant difference in serum matrix metalloproteinases 2 and 9 was found between cases and controls.

Conclusions:

• Rhesus macaque large intestinal carcinomas exhibit significant histomorphologic and immunohistochemical similarities to human colorectal tumors.
• These findings support the rhesus macaque as a valuable preclinical model for human colorectal cancer.
• Further validation is crucial for developing novel therapeutics and understanding disease pathogenesis.