Enhanced expression of CD74 in gastrointestinal cancers and benign tissues

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 neo-plasia, and provide a rationale for development of therapeutic agents that are able to block CD74 function, specifically within the tumor cell.