Parathyroid Hormone-Related Protein and Serum Calcium in Patients with Renal Cell Carcinoma

Abstract

Objective: To evaluate serum parathyroid hormone-related protein (PTHrP) in relation to serum calcium and clinical outcome of patients with renal cell carcinoma.Methods: Sera from 243 patients with renal cell carcinoma were collected prior to therapy. Serum PTHrP was analyzed using an immunoradiometric assay. Tumour stage, nuclear grade, corrected serum calcium, and survival were assessed. Results: Serum PTHrP was detectable in 37/243 sera (15%) and hypercalcaemia (≧2.60 mmol/l) in 32/220 (15%). A positive correlation between serum PTHrP and serum calcium was found (r = 0.326; p < 0.01). Following subdivision of the material, based on storage time, the frequency of detectable serum PTHrP seemed to decrease with time. Serum calcium, but not serum PTHrP, was correlated to tumour stage (p < 0.001). Survival was similar for patients with detectable and undetectable PTHrP, but those with hypercalcaemia had a significantly shorter survival time compared to those with normal serum calcium (p < 0.001). A multivariate analysis showed that tumour stage and serum calcium were independent prognostic factors, but not grade or PTHrP. Conclusions: A positive relation of serum PTHrP to serum calcium was demonstrated in patients with renal cell carcinoma. Hypercalcaemia but not serum PTHrP predicted a worse prognosis.

Putative Biomarker Genes for Grading Clear Cell Renal Cell Carcinoma

“…Similarly PTHLH, synonymously called parathyroid hormone-related protein, whose receptor is responsible for hypercalcemia of malignancy [32][33][34] , was found to be upregulated as well. Hypercalcemia is a part of paraneoplastic syndromes in RCC, underlined by an upregulation of associated gene products, eventually potential markers for advanced stages of RCC.…”

Renal Cell Carcinoma Presenting with Paraneoplastic Hypercalcemic Coma: A Case Report and Review of the Literature

“…15,16 Hypercalcemia is the most common paraneoplastic complication of RCC, and approximately 17% of all patients with RCC develop hypercalcemia during the course of their disease. [17][18][19] Albright 20 first reported hypercalcemia occurring in a patient with RCC in 1941. He postulated that the hypercalcemia was because of a humoral factor secreted by the tumor.…”

“…26 It is reported that PTHrP levels are elevated in up to 47% of patients with malignancy and hypercalcemia. 27 Parathyroid hormone-related peptide is elevated in up to 15% of all patients with RCC, 19 but it is also expressed in normal tissue. 28 This Figure 2.…”

Skeletal metastasis: Established and emerging roles of parathyroid hormone related protein (PTHrP)

“…In contrast, tumors of the clear cell type were found to express PTHrP to a significantly greater extent than tumors of the granular cell type. Papworth et al detected PTHrP in the sera of 15% of 243 renal cell carcinoma patients [64]. A trend of hypercalcemia was found in the patients with PTHrP, but although serum PTHrP positively correlated with serum calcium, it did not correlate with tumor stage.…”

“…Several reports supported that increased PTHrP levels in serum and urine could be useful indicators of hypercalcemia, bone metastasis and prognosis in lung cancer patients [58,94,95]. Increased PTHrP in serum was also identified in sera of patients with prostate carcinoma [96], renal cell carcinoma [64], and melanoma [97]. The prognostic value isn't quite clear in breast cancer, since PTHrP is reported to be either positively or negatively associated with prognosis.…”