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Serum parathyroid hormone‐related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma
Author(s) -
Deans Chris,
Wigmore Stephen,
PatersonBrown Simon,
Black James,
Ross James,
Fearon Kenneth C. H.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20972
Subject(s) - medicine , parathyroid hormone , carcinoma , gastroenterology , malignancy , parathyroid hormone related protein , systemic inflammation , radioimmunoassay , endocrinology , inflammation , parathyroid carcinoma , serum amyloid a , cytokine , serum albumin , adverse effect , calcium
BACKGROUND Parathyroid hormone‐related peptide (PTHrP) is a tumor‐derived circulating factor that has been associated with hypercalcemia of malignancy. The role of PTHrP as a prognostic indicator remains unclear. Studies suggest that it may function as a growth factor; and, recently, the ability of PTHrP to induce cytokine expression has been described. PTHrP also has been proposed as a procachectic factor. In this study, the authors investigated the prognostic value of PTHrP in patients who had gastroesophageal carcinoma without hypercalcemia and determined whether PTHrP was associated with systemic inflammation and adverse nutritional status. METHODS Patients were recruited at the time of diagnosis. Serum was collected for determination of c‐terminal fragment PTHrP (cPTHrP) levels (by radioimmunoassay) and calcium levels as well as levels of serum cytokines and acute‐phase proteins (with an enzyme‐linked immunosorbent assay). Nutritional assessment of patients was undertaken at the same time as serum collection. Patients underwent routine staging, and survival duration was recorded. RESULTS One hundred fifty‐one patients with esophagogastric carcinoma were recruited. Six of 151 patients (4.0%) patients were hypercalcemic, and 26 patients (17.2%) had elevated serum cPTHrP levels. There was no association between the cPTHrP level and either serum calcium concentrations ( P = 0.72) or adverse nutritional status. Elevated cPTHrP, however, was associated with significantly higher serum levels of soluble tumor necrosis factor receptor ( P = 0.008) and with significantly lower levels of transferrin ( P = 0.009) and albumin ( P = 0.02). There was also a weak association with C‐related protein levels ( P = 0.06). Elevated cPTHrP levels also were associated with an adverse prognosis, as determined by reduced survival duration, on univariate analysis ( P = 0.038), but not on multivariate analysis ( P = 0.15). CONCLUSIONS Elevated serum cPTHrP levels were present in approximately 17% of patients with gastroesophageal carcinoma in the absence of hypercalcemia and was associated with markers of systemic inflammation and with an adverse prognosis. Cancer 2005. © 2005 American Cancer Society.