Ectopic Expression of reg Protein: A Marker of Colorectal Mucosa at Risk for Neoplasia

Pancreatic regenerating gene (reg I) messenger RNA is overexpressed within the pancreas following injury and resection. Its level of expression corresponds to the level of cellular dedifferentiation. Human reg I has been localized to chromosome 2p12, and ectopic expression of its mRNA has been found within colorectal tumors. We postulated that colorectal production of reg I might either be a marker for the presence of cancer or define mucosa at risk for development of neoplasia. Using a monoclonal antibody to reg I, regenerating gene protein was histochemically mapped in 56 cases of documented colorectal adenocarcinoma. In sections of colon from normal control subjects no reg I protein was noted, whereas 58.9% of the specimens from cancer patients stained positive for reg I. Although a correlation was noted between reg I staining and Dukes' stage, there was no correlation with histologic grade or 5-year patient survival. In 39 of 55 cancer specimens the transition zone (interface) between the neoplasm and normal mucosa was visualized; 100% of the transition zones contained cells that stained strongly positive for reg I. We conclude that reg I protein is ectopically expressed in colorectal mucosa at the transition zone of colorectal cancer, and occasionally within the tumor itself. Although ectopic reg I expression in colorectal epithelia is not a marker for the presence of carcinoma, it may be a sensitive marker for mucosa at risk for development of neoplasia.