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Int J Clin Exp Pathol 2011;4(1):1-12

Original Article
Enhanced expression of CD74 in gastrointestinal cancers and benign tissues

David V. Gold, Rhona Stein, Jack Burton, David M. Goldenberg

Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ, USA 07109, USA

Received November 18, 2010; accepted November 21, 2010; Epub November 23, 2010; published January 1, 2011

Abstract: CD74, a transmembrane glycoprotein that associates with MHC II, is an important chaperone that regulates antigen presentation for
immune response. In addition, CD74 is the receptor for macrophage migration-inhibitory factor which, when bound to CD74, initiates survival
pathways and cell proliferation.  Formalin fixed, paraffin embedded clinical specimens were evaluated by immunohistochemical procedures for
expression of CD74. Overall, expression of CD74 within gastrointestinal carcinomas showed a statistically greater expression than in the
normal tissue counterparts (P<0.001 or better). CD74 expression was observed in 95% of pancreatic carcinomas with the majority of cases
presenting a mostly intense, diffuse labeling pattern.  The results suggested a trend towards greater expression within the higher grade
carcinomas (P=0.06).  Colorectal and gastric carcinomas gave similar results with 60% and 86%, respectively, positive for CD74 with an
intense, diffuse staining pattern.  We hypothesized that precursor lesions would express levels of CD74 as high, or higher, than their respective
carcinomas, since activation of survival pathways would be of particular importance at the early stages of neoplastic development. For PanIN
lesions there was greater expression of CD74 within higher grade, PanIN-3 lesions, whereas the colonic adenomas showed no such trend,
but overall, a higher frequency and intensity of CD74 labeling than was observed within the colon carcinomas.  These findings are supportive of
a role for CD74 in the development and maintenance of gastrointestinal neoplasia, and provide a rationale for development of therapeutic
agents that are able to block CD74 function, specifically within the tumor cell. (IJCEP1011004).

Keywords: CD74, invariant chain, pancreatic carcinoma, colon carcinoma, gastric carcinoma

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Address all correspondence to:
David V. Goldenberg, MD, PhD
Garden State Cancer Center
520 Belleville Avenue
Belleville, NJ 07109, USA.
Tel: 973-844-7002; Fax: 973-844-7020