Clinicopathological implications of parathyroid hormone-related protein inhuman colorectal tumours

The purpose of the present study was to clarify the relationship of parathy roid hormone-related protein (PTHrP) to the oncogenesis and progression of colorectal adenocarcinoma. A total of 108 colorectal tumours, including 12 adenomas, six adenocarcinomas in adenomas, and 90 adenocarcinomas,were stud ied. Immunohistochemistry, in situ hybridization, and reverse transcription -polymerase chain reaction (RT-PCR) techniques were used to evaluate the ex pression of PTHrP. Positivity of immunostaining for PTHrP was defined as hi ghly positive (+ +), slightly positive (+), and negative (-). None of the a denomas of background non-neoplastic mucosal epithelia showed immunostainin g of PTHrP. In contrast, PTHrP was expressed in 85 (94.4 per cent) of 90 co lorectal adenocarcinomas. Immunoreactivity of PTHrP was greater in poorly d ifferentiated adenocarcinomas than in well-differentiated ones. Furthermore , advancing margins of primary tumours stained more intensely than other si tes. Highly positive immunoreactivity of PTHrP, classified by histological invasiveness, was 22.6 per cent within the muscularis propria and 69.5 per cent beyond the muscularis propria. PTHrP expression was significantly corr elated with differentiation, depth of invasion, lymphatic invasion, lymph n ode metastasis, hepatic metastases, and Dukes' classification. In carcinoma , PTHrP mRNA expression was evident in tumour cells by irt situ hybridizati on. PTHrP transcripts mere also detected in two resected human colorectal a denocarcinomas by RT-PCR. These findings suggest that PTHrP is related to c arcinogenesis, differentiation, progression, and prognosis of colorectal ad enocarcinomas. Copyright (C) 1999 John Wiley & Sons, Ltd.