title: Expression of parathyroid hormone-related protein (PTHrP) in multiple myeloma.
abstract: Multiple myeloma is a plasma cell neoplasia often associated with multiple skeletal lesions and hypercalcemia. Several cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor-beta (TNF-beta), derived from myeloma cells are thought to accelerate osteoclastic bone resorption and cause hypercalcemia through a paracrine mechanism. We report on a case of a 69-year-old man with multiple myeloma associated with hypercalcemia and advanced osteolytic lesions. After bisphosphonate treatment and MP (melphalan and prednisolone) therapy, the patient's serum calcium level was successfully but transiently recovered to the normal range. Biochemical analysis showed a remarkable increase in serum parathyroid hormone-related protein (PTHrP; 3.7 pmol/L) and IL-6 (22.0 pg/mL). On the other hand, parathyroid hormone and 1alpha,25(OH)2 vitamin D3 were suppressed. By immunohistochemistry and in situ hybridization on aspiration-biopsied bone marrow clot sections, PTHrP mRNA and protein were detected in the cytoplasm of myeloma cells. The rate of PTHrP-positive myeloma cells was estimated to be at least one-third. Since PTHrP can, as an endocrine factor, systemically act on bone and kidney, hypercalcemia in this case might have been caused through both local osteolytic hypercalcemia and humoral hypercalcemia of malignancy mechanisms.
authors.affiliation: Division of Molecular Pathology Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kajimoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Tosimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Sakan
authors.initials: S
authors.lastname: Maeda
mesh_terms: D000368:Aged; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins