PARATHYROID HORMONE-RELATED PEPTIDE EXPRESSION IN PRIMARY AND METASTATIC LIVER-TUMORS

Parathyroid hormone-related peptide (PTHrP) is a major factor in the p athophysiology of hypercalcaemia of malignancy. Recent evidence sugges ts that PTHrP may play an important role in the growth and differentia tion of neoplastic as well as non-neoplastic cells. PTHrP was original ly detected in normal fetal, but not adult, liver. We have used immuno cytochemistry to show that reactive human bile ductules expressing a n euroendocrine phenotype contain immunoreactive PTHrP. These observatio ns raised the possibility that PTHrP immunoreactivity may be useful in the differential diagnosis of primary liver rumours and metastases of adenocarcinoma. A total of 24 primary liver tumours and 22 metastases of adenocarcinoma were studied. All cholangiocarcinomas showed immuno positivity for PTHrP and chromogranin A, while all hepatocellular carc inomas were negative for PTHrP and showed only focal and weak positivi ty for chromogranin A. Mixed types of primary liver tumour contained P THrP immunoreactivity only in the areas of cholangiocellular different iation. Moreover, all metastatic adenocarcinomas were negative for PTH rP and chromogranin A except for two out of five metastatic breast ade nocarcinomas. These two patients had bone metastases and hypercalcaemi a and thus did not yield differential diagnostic problems with cholang iocarcinoma. None of the patients with cholangiocarcinoma and hepatoce llular carcinoma had hypercalcaemia. We conclude that PTHrP is a usefu l marker for primary cholangiocarcinoma, especially in the differentia l diagnosis of hepatocellular carcinoma and metastatic adenocarcinoma.