Parathyroid hormone–related protein expression is correlated with clinical course in patients with glial tumors

Abstract

BACKGROUNDParathyroid hormone–related protein (PTHrP) expression modulates cell survival in a number of human solid tumors. Although PTHrP is expressed in normal developing and neoplastic central nervous system tissue, clinical data indicating the importance of this protein with respect to local control and/or survival in patients with glial tumors are scarce.METHODSUsing a standard immunoperoxidase technique, the authors examined PTHrP expression in a population of 51 patients with Daumas–Duport Grade II–IV astrocytomas over a 15‐year period. Both local control and survival were calculated from the date of definitive irradiation to the last time of known follow‐up examination using the actuarial method. PTHrP expression was scored on examination under 40× magnification, with the incidence of cellular staining averaged over 10 high‐power fields. The intensity and extent of staining were characterized semiquantitatively using the standard World Health Organization classification criteria. The median follow‐up duration was approximately 5.5 years. Multivariate analyses were performed to ascertain the statistical significance of several standard clinicohistopatholgic factors (Karnofsky functional status, age, gender, extent of surgical resection, radiotherapy dose, grade, and PTHrP expression) with respect to local control and survival. P < 0.05 was considered indicative of statistical significance.RESULTSPatients with high levels of PTHrP expression had significantly lower glial tumor local control rates and corresponding decreases in progression‐free and overall actuarial survival after definitive irradiation (P < 0.01). In a Cox 3‐variable model, the PTHrP staining score was independent of tumor grade or Karnofsky functional status. It is notable that the strongest predictor of survival was tumor grade (P < 0.001).CONCLUSIONSPTHrP may be an important adjunct to standard immunopathologic criteria in the determination of glial tumor responses. A number of mechanisms were explored to derive a more mechanistic understanding of these translational results. Subsequent prospective studies involving larger patient populations will be necessary before findings can be translated to clinical practice. Cancer 2004. © 2004 American Cancer Society.

A review of clinical and molecular prognostic factors in osteosarcoma

“…So far no study has adequately assessed the prognostic bearing of PTHrP/PTHR1 in osteosarcoma, however mixed results have been seen in more common tumours. Patients with glial tumours were observed to have a signiWcantly reduced overall survival with elevated PTHrP expression (Pardo et al 2004), and in a study of patients with hypercalcaemia of malignancy, PTHrP levels corresponded with a poor prognosis (Truong et al 2003). On the other hand, over expression of PTHrP in a rat osteoblastic, osteosarcoma cell line was found to reduce cell proliferation by 80% (Pasquini et al 2002).…”

Parathyroid hormone‐related protein as a potential tumor marker: A case report of ovarian clear cell carcinoma

“…Several reports indicate that carcinoma which has potential of PTHrP production is predicted as their poor prognosis in breast cancer, 11,12 renal carcinoma, 13 and glial tumors, 14 and as their poor response to antihypercalcemic therapy by bisphosphonate 15 . A prospective study of hypercalcemic cancer patients reported that an elevated PTHrP level was a strong prognostic indicator, independent of elevated serum calcium levels 16 .…”

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“…PTHrP is also present in glia and astrocytes. High PTHrP levels in glial tumors correlate with a poor prognosis [82][83][84][85]. PTHrP expression increases in sites of ischemic brain injury where it may play a protective role by enhancing blood flow [83].…”