Endocrine markers in malignant tumor cells producing parathyroid hormone-related protein

Humoral hypercalcemia of malignancy may reflect the synthesis and secretion of biologically active parathyroid hormone-related protein (PTHrP) by a given tumor. In the present study we investigated 25 human non-endocrine carcinomas which were clinically associated with hypercalcemia (Ca > 11 mg%). By applying PTHrP-specific immunocytochemistry, PTHrP could be detected in all tumors. The intra-tumorous distribution was heterogeneous with strong positivity in relatively few cells or weak positivity in the majority of cells. Surprisingly, in the PTHrP producing cells none of the marker proteins typical of endocrine cells (neuron-specific enolase, Leu-7 antigen, chromogranin, synaptophysin and endocrine granule constituent) was found. On the other hand, PTHrP producing cells of endocrine origin, such as medullary cancer, or normal and adenomatous parathyroid glands, all produce these endocrine markers. Thus for the first time, the existence of peptide hormone producing tumor cells is reported without expression of endocrine markers. This indicates a special mechanism of PTHrP secretion.