Hypercalcemia in patients with esophageal carcinoma. The pathophysiologic role of parathyroid hormone-related protein.

To elucidate the actual incidence of hypercalcemia in patients with esophageal carcinoma, 382 consecutive cases admitted to the National Cancer Center Hospital (Tokyo, Japan) from 1983 to 1988 were investigated. Hypercalcemia was detected in 5 patients of 376 (1.3%) at the time of primary detection of cancer, and in 45 patients of 120 (38%) patients with recurrent or unresectable cancer who were monitored within 2 months of death. These observations demonstrated that this electrolyte imbalance is a frequent paraneoplastic syndrome observed in patients with advanced esophageal carcinoma. With regard to the etiology, bone metastases were detected in 13 of 49 patients with hypercalcemia; the remaining 36 patients were assumed to be induced by the production of hypercalcemic substance(s) by tumor tissues. Parathyroid hormone-related protein (PTHrP) is a newly discovered factor which increases serum calcium in vivo. The detection of PTHrP mRNA in tumor tissues as well as the production of PTHrP-like immunoreactivity by tumor tissues were closely associated with the development of hypercalcemia, suggesting that PTHrP is the major cause of hypercalcemia in patients with esophageal carcinoma.