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

Francisco S. Pardo, Winston W. Lien, Howard S. Fox, Jimmy T. Efird, Joseph A. Aguilera, Douglas W. Burton, Leonard J. Deftos

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND. Parathyroid 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. METHODS. Using 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 40x 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. RESULTS. 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). CONCLUSIONS. 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.

Original languageEnglish (US)
Pages (from-to)2622-2628
Number of pages7
JournalCancer
Volume101
Issue number11
DOIs
StatePublished - Dec 1 2004

Fingerprint

Parathyroid Hormone-Related Protein
Neuroglia
Neoplasms
Survival
Staining and Labeling
Nerve Tissue
Astrocytoma
Glioblastoma
Immunoenzyme Techniques
Population
Cell Survival
Radiotherapy
Multivariate Analysis
Central Nervous System
Prospective Studies
Incidence

Keywords

  • Central nervous system
  • Glial tumors
  • Immunopathologic criteria
  • Parathyroid hormone-related protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pardo, F. S., Lien, W. W., Fox, H. S., Efird, J. T., Aguilera, J. A., Burton, D. W., & Deftos, L. J. (2004). Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors. Cancer, 101(11), 2622-2628. https://doi.org/10.1002/cncr.20689

Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors. / Pardo, Francisco S.; Lien, Winston W.; Fox, Howard S.; Efird, Jimmy T.; Aguilera, Joseph A.; Burton, Douglas W.; Deftos, Leonard J.

In: Cancer, Vol. 101, No. 11, 01.12.2004, p. 2622-2628.

Research output: Contribution to journalArticle

Pardo, FS, Lien, WW, Fox, HS, Efird, JT, Aguilera, JA, Burton, DW & Deftos, LJ 2004, 'Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors', Cancer, vol. 101, no. 11, pp. 2622-2628. https://doi.org/10.1002/cncr.20689
Pardo, Francisco S. ; Lien, Winston W. ; Fox, Howard S. ; Efird, Jimmy T. ; Aguilera, Joseph A. ; Burton, Douglas W. ; Deftos, Leonard J. / Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors. In: Cancer. 2004 ; Vol. 101, No. 11. pp. 2622-2628.
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abstract = "BACKGROUND. Parathyroid 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. METHODS. Using 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 40x 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. RESULTS. 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). CONCLUSIONS. 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.",
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AU - Aguilera, Joseph A.

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AU - Deftos, Leonard J.

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AB - BACKGROUND. Parathyroid 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. METHODS. Using 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 40x 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. RESULTS. 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). CONCLUSIONS. 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.

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