002l-972X/91/7306-1309$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright (p) 1991 by The Endocrine Society
Vol. 73, No. 6 Printed in U.S.A.
Parathyroid Hormone-Related Protein: Elevated Levels in both Humoral Hypercalcemia of Malignancy and Hypercalcemia Complicating Metastatic Breast Cancer* V. GRILL, P. HO, J. J. BODY, N. JOHANSON, S. C. LEE, S. C. KUKREJA, J. M. MOSELEY, AND T. J. MARTIN Department of Medicine, St. Vincent's Institute of Medical Research, St. Vincent's Hospital, Fitzroy, Australia 3065; the Unit of Endocrinology and Metabolisin, Institute Jules Bordet, Centre des Tumeurs de I'Uniuersite Libre de Bruxelles (J.J.B.), 1000 Brussels, Belgium; Incstar Corp. (S.C.L.), Stillwater, Minnesota 45082; and the Endocrinology Section, Veterans Administration Medical Center (S.C.K.), Chicago, Illinois 60680
ABSTRACT. A RIA for PTH-related protein (PTHrP) is described, using a polyclonal goat antiserum against synthetic PTHrP-(l-40) and recombinant PTHrP-(l-84) as standard. The detection limit is 2 pmol/L, and intra- and interassay coefficients of variation are 4.8% and 13.6%, respectively. This assay does not detect PTH even at concentrations of up to 2000 pmol/L. Cross-reactivity studies using various synthetic PTHrP peptides localize the antibody-binding epitope between residues 20 and 29. Hypercalcemic patients with a range of solid tumors and no evidence of bone metastases on radionuclide scanning (n = 27) all had detectable PTHrP levels (range, 2.8-51.2 pmol/L). Of 17 patients with solid tumors (other than breast) and bone metastases, 11 (64%) also had detectable PTHrP levels (range, 4.947.5 pmol/L). Twenty samples from breast cancer patients with hypercalcemia, 19 with evidence of bone metastases, and 1 with a negative bone scan were assayed, and detectable PTHrP levels
H
YPERCALCEMIA as a complication of malignancy has long been recognized (1). In discussing a patient with renal carcinoma and hypercalcemia, Albright (2) suggested that the tumor might be producing PTH. A novel PTH-related protein has now been isolated, its cDNA cloned, and its gene mapped (3-8). The PTHrP gene gives rise by alternative splicing to multiple mRNA species encoding three mature proteins of 139, 141, and 173 amino acids (5, 8-10). The amino acid sequence of PTHrP bears 60% homology with that of PTH over the first 13 amino acids, and the PTH-like biological activity of PTHrP is contained within the first Received January 23,1991. Address all correspondence and requests for reprints to: Prof. T. J. Martin, Department of Medicine, St. Vincent's Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia. * This work was supported by the National Health and Medical Research Council of Australia, the Anti-Cancer Council of Victoria (Australia), and an award from St. Vincent's Hospital Research Grant Committee.
were found in 13 (65%; range, 3.8-61.6 pmol/L). Patients with squamous cell carcinomata and normal serum calcium levels (n = 11) had no detectable PTHrP or levels close to the detection limit of the assay (range,
Vol. 73, No. 6 Printed in U.S.A.
Parathyroid Hormone-Related Protein: Elevated Levels in both Humoral Hypercalcemia of Malignancy and Hypercalcemia Complicating Metastatic Breast Cancer* V. GRILL, P. HO, J. J. BODY, N. JOHANSON, S. C. LEE, S. C. KUKREJA, J. M. MOSELEY, AND T. J. MARTIN Department of Medicine, St. Vincent's Institute of Medical Research, St. Vincent's Hospital, Fitzroy, Australia 3065; the Unit of Endocrinology and Metabolisin, Institute Jules Bordet, Centre des Tumeurs de I'Uniuersite Libre de Bruxelles (J.J.B.), 1000 Brussels, Belgium; Incstar Corp. (S.C.L.), Stillwater, Minnesota 45082; and the Endocrinology Section, Veterans Administration Medical Center (S.C.K.), Chicago, Illinois 60680
ABSTRACT. A RIA for PTH-related protein (PTHrP) is described, using a polyclonal goat antiserum against synthetic PTHrP-(l-40) and recombinant PTHrP-(l-84) as standard. The detection limit is 2 pmol/L, and intra- and interassay coefficients of variation are 4.8% and 13.6%, respectively. This assay does not detect PTH even at concentrations of up to 2000 pmol/L. Cross-reactivity studies using various synthetic PTHrP peptides localize the antibody-binding epitope between residues 20 and 29. Hypercalcemic patients with a range of solid tumors and no evidence of bone metastases on radionuclide scanning (n = 27) all had detectable PTHrP levels (range, 2.8-51.2 pmol/L). Of 17 patients with solid tumors (other than breast) and bone metastases, 11 (64%) also had detectable PTHrP levels (range, 4.947.5 pmol/L). Twenty samples from breast cancer patients with hypercalcemia, 19 with evidence of bone metastases, and 1 with a negative bone scan were assayed, and detectable PTHrP levels
H
YPERCALCEMIA as a complication of malignancy has long been recognized (1). In discussing a patient with renal carcinoma and hypercalcemia, Albright (2) suggested that the tumor might be producing PTH. A novel PTH-related protein has now been isolated, its cDNA cloned, and its gene mapped (3-8). The PTHrP gene gives rise by alternative splicing to multiple mRNA species encoding three mature proteins of 139, 141, and 173 amino acids (5, 8-10). The amino acid sequence of PTHrP bears 60% homology with that of PTH over the first 13 amino acids, and the PTH-like biological activity of PTHrP is contained within the first Received January 23,1991. Address all correspondence and requests for reprints to: Prof. T. J. Martin, Department of Medicine, St. Vincent's Hospital, Victoria Parade, Fitzroy, Victoria 3065, Australia. * This work was supported by the National Health and Medical Research Council of Australia, the Anti-Cancer Council of Victoria (Australia), and an award from St. Vincent's Hospital Research Grant Committee.
were found in 13 (65%; range, 3.8-61.6 pmol/L). Patients with squamous cell carcinomata and normal serum calcium levels (n = 11) had no detectable PTHrP or levels close to the detection limit of the assay (range,
