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- Title
Parathyroid hormonerelated protein expression is correlated with clinical course in patients with glial tumorsPresented in part at the 45th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Salt Lake City, UT, October 1923, 2003.The opinions expressed herein do not necessarily reflect the views of the National Institutes of Health or the U.S. Government.
- Authors
Francisco S. Pardo; Winston W. Lien; Howard S. Fox; Jimmy T. Efird; Joseph A. Aguilera; Douglas W. Burton; Leonard J. Deftos
- Abstract
Parathyroid hormonerelated 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.Using a standard immunoperoxidase technique, the authors examined PTHrP expression in a population of 51 patients with DaumasDuport Grade IIIV 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.Patients 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).PTHrP 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.
- Subjects
PARATHYROID hormone-related protein; CENTRAL nervous system tumors; CANCER cells; TUMORS; ASTROCYTES; GENE expression
- Publication
Cancer (0008543X), 2004, Vol 101, Issue 11, p2622
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.20689