Zabel M, Dietel M
Department of Histology, University of Medicine, Poznan, Poland.
Exp Clin Endocrinol. 1993;101(5):297-302. doi: 10.1055/s-0029-1211247.
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.
恶性肿瘤所致的体液性高钙血症可能反映了特定肿瘤合成并分泌具有生物活性的甲状旁腺激素相关蛋白（PTHrP）。在本研究中，我们调查了25例临床上伴有高钙血症（血钙>11mg%）的人类非内分泌癌。通过应用PTHrP特异性免疫细胞化学方法，在所有肿瘤中均检测到了PTHrP。肿瘤内分布不均一，相对少数细胞呈强阳性，而大多数细胞呈弱阳性。令人惊讶的是，在产生PTHrP的细胞中，未发现任何内分泌细胞典型的标志物蛋白（神经元特异性烯醇化酶、Leu-7抗原、嗜铬粒蛋白、突触素和内分泌颗粒成分）。另一方面，内分泌起源的产生PTHrP的细胞，如髓样癌，或正常及腺瘤样甲状旁腺，均产生这些内分泌标志物。因此，首次报道了存在产生肽类激素的肿瘤细胞而无内分泌标志物表达的情况。这表明了PTHrP分泌的一种特殊机制。
