Serum parathyroid hormone-related peptide is associated with systemic inflammation and adverse prognosis in gastroesophageal carcinoma.
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.
Deans
Chris
C
Tissue Injury and Repair Group, Medical Research Council Centre for Inflammation Research, Department of Clinical and Surgical Sciences, Medical School, Edinburgh University, Edinburgh, United Kingdom.
Wigmore
Stephen
S
Paterson-Brown
Simon
S
Black
James
J
Ross
James
J
Fearon
Kenneth C H
KC
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000378:metabolism; D002118:Calcium / Q000097:blood; D018288:Carcinoma, Small Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004938:Esophageal Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D004943:Esophagogastric Junction / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D011379:Prognosis; D011863:Radioimmunoassay; D013274:Stomach Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D014168:Transferrin / Q000378:metabolism
D000418:Albumins; D016207:Cytokines; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D014168:Transferrin; D002118:Calcium