PARATHYROID HORMONE-RELATED PROTEIN EXPRESSION IN THE HUMAN COLON - IMMUNOHISTOCHEMICAL EVALUATION

Parathyroid hormone-related protein (PTHrP) has been shown to be the p rimary factor responsible for humoral hypercalcemia of malignancy In a ddition to its hypercalcemic action, PTHrP has been implicated as an a utocrine modulator of growth and differentiation, as well as an early response gene in some tissues. Several different types of tumors have been evaluated for the presence of PTHrP immunoreactivity. In the pres ent study, we evaluated the expression of PTHrP by immunohistochemical staining in tissue samples from normal colorectal mucosa, polyps, and colorectal carcinoma removed from the same patients (n = 10 each). We have used a commercially available monoclonal antibody directed again st epitopes between amino acids [53-64] which share no homology to par athyroid hormone (PTH), In normal colon, 94.3 per cent of the tissue s amples were negative for PTHrP immunoreactivity. In polyps of the colo n, only 22.6 per cent of the cells showed positive immunostaining wher eas 91.5 per cent of the samples from colon cancer stained positive fo r PTHrP. In the case of polyps, the intensity of staining was 1-3+; ho wever, all of the samples from adenocarcinoma stained with 4+ intensit y. In the positive samples, the immunoreactivity was present throughou t the cytoplasm of the glandular epithelium. Omission of primary antib ody, as well as substitution of the primary antibody by a negative con trol monoclonal antibody or non-immune rabbit serum, resulted in a neg ative reaction. All analyses were performed in duplicate, and the data have been presented as mean +/- SEM. Differences in normal polyps, ca rcinoma of the colon, and PTHrP expression were tested for statistical significance by student's t test. Our results show the expression of PTHrP is enhanced in colon cancer tissue as compared-to normal colorec tal mucosa and polyps. In addition, the expression appears to be great er in polyp than in normal colon. The role of PTHrP in the pathogenesi s of colon cancer deserves further study.