Do phosphatase of regenerating liver-3, matrix metalloproteinases-2, matrix metalloproteinases-9, and epidermal growth factor receptor-1 predict response to therapy and survival in glioblastoma multiforme?

Indian J Pathol Microbiol. 2016 Jul-Sep;59(3):287-93. doi: 10.4103/0377-4929.188121.

Abstract

Context: Poor survival of the glioblastoma multiforme (GBM) has been attributed in part to the invasive nature of the lesion making complete surgical removal near impossible. Phosphatase of regenerating liver-3 (PRL-3), matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9), and epidermal growth factor receptor (EGFR-1) play a role in invasive nature of tumor cells.

Aims: This study was conducted to evaluate PRL-3, MMP-2, MMP-9, and EGFR-1 (markers) expression in cases to GBM and to correlate their expression with therapy response and survival.

Settings and design: GBM cases (n = 62) underwent surgery followed by radiation (n = 34) and chemoradiation (n = 28). Using WHO Response Evaluation Criteria in Solid Tumors criteria response to therapy was assessed at 3 months and cases followed up for survival.

Subjects and methods: Expression of markers was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots.

Statistical analysis used: Kaplan-Meier, ANOVA, Chi-square test, univariate, and multivariate Cox-regression analysis was done.

Results: Response to therapy was evident in 54.8% cases of responders with the mean survival of 494.03 ± 201.13 days and 45.2% cases of non responders (278.32 ± 121.66 days) with P = 0.001. Mean survival for the patient's opted chemoradiation was 457.43 ± 222.48 days which was approximately 3 months greater than those who opted radiation alone (P = 0.029). We found PRL-3 overexpression was an independent, significant, poor prognostic factor for survival by multivariate analysis (P = 0.044). Cases negative for MMP's and EGFR showed increased survival, but the difference was insignificant.

Conclusion: PRL-3 expression appears to be related to an adverse disease outcome.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • ErbB Receptors / analysis*
  • Female
  • Follow-Up Studies
  • Glioblastoma / diagnosis*
  • Glioblastoma / mortality
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • Immunohistochemistry
  • Infant
  • Male
  • Matrix Metalloproteinases / analysis*
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Prognosis
  • Protein Tyrosine Phosphatases / analysis*
  • Radiotherapy
  • Surgical Procedures, Operative
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Neoplasm Proteins
  • ErbB Receptors
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases
  • Matrix Metalloproteinases