Cancer and the Vasopressin Gene: Radioimmunoassay Values and Commentary on Copeptin as a Plasma Marker

Vasopressin gene expression has been demonstrated to be a common feature of all small-cell lung cancer (SCLC) and breast cancer. Provasopressin (ProVP) is a component of the cancer cell membrane and a likely target for treatment. However, a measurable fraction of this cancer provasopressin is also normally processed and products are released into the circulation. Vasopressin (VP) and vasopressin-associated human neurophysin (VP-HNP), two of three products of processing, were earlier shown to be reliable plasma markers for determining the presence of SCLC and monitoring response to treatment.

In this study, copeptin, the third product of provasopressin processing, was preliminarily evaluated as a plasma marker for SCLC or breast cancer using radioimmunoassay (RIA). Antibodies directed against the 18 residue C-terminal peptide fragment of copeptin were used to avoid interference from the large-carbohydrate component of this endogenous glycopeptide.

The levels of copeptin in 8 male and 6 female patients with SCLC before treatment ranged from 16 to 319 pmol/L, and these levels were elevated (>2.5 times) in 10 of 14 cases (70%) when compared with healthy volunteers (normal mean, 18 ± 6 pmol/L). Volunteer values for males were smaller than for females (15± 4 pmol/L and 20± 9 pmol/L), but numbers were small. Patients with breast cancer had plasma levels ranging from 12 to 68 pmol/L, with only three of the six elevated.

While cancer patients displayed a wide range of plasma copeptin levels over 70% with SCLC and 50% with breast cancer had clearly elevated levels. This finding indicates that for such patients, plasma copeptin, like plasma VP and VP-HNP, could be used to detect disease. The control values found for healthy volunteers using our RIA were in a range predictable from established normal plasma levels of both VP and VP-HNP.