Prognostic Value of ALDH1, EZH2 and Ki-67 in Astrocytic Gliomas

Turk Patoloji Derg. 2016;32(2):70-81. doi: 10.5146/tjpath.2015.01344.

Abstract

Objective: Tumor stem cells have been found in a variety of neoplasms and stated to have a role in tumor progression. This study aimed to evaluate the prognostic significance of biomarkers which are said to be related to these cells, i.e., EZH2, ALDH1 and Ki-67, and their correlation with each other in astrocytic gliomas.

Material and method: Formalin-fixed, paraffin-embedded tissue specimens of 40 patients with astrocytic glioma who underwent initial surgery during the period from December 2011 to May 2014 at Zagazig University Hospitals were enrolled in the study. Consecutive 4-μm thick sections from formalin-fixed, paraffin-embedded tissue blocks were prepared and stained with hematoxylin and eosin for histopathological evaluation. Immunohistochemical analysis using ALDH1, EZH2 and Ki-67 antibodies were performed to examine the cases.

Results: A total of forty patients; 22 males and 18 females were studied. The lesions were classified as follows: 14 cases of low-grade astrocytoma (WHO grade I or II), 11 cases of anaplastic astrocytoma (WHO grade III), and 15 glioblastomas (WHO grade IV). There was a significant increase in ALDH1 immunoreactivity with increasing the grade of astrocytoma (mean ±SD = 0.2 ±0.4, 0.5 ±0.6, 1.1 ±1.3 and 2.95 ±2.97 in grade I to IV astrocytic gliomas, respectively). This expression was significantly correlated with overall survival (OS) and progression-free survival (PFS) (P=0.004). EZH2 expression was also significantly associated with advanced grades (mean ±SD =1.35 ±0.4, 3.1 ±2.6, 7.2 ±3.5 and 9.9 ±4.1, in grade I to IV astrocytic gliomas, respectively). EZH2 and Ki-67 expressions were found to be correlated with OS and PFS (P < 0.001).

Conclusion: Increased expression of ALDH1, EZH2 and KI67 are found to be associated with unfavourable prognosis in patients with astrocytic gliomas and may predict therapeutic modalities.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aldehyde Dehydrogenase 1 Family
  • Astrocytoma / mortality
  • Astrocytoma / pathology*
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Child
  • Disease-Free Survival
  • Enhancer of Zeste Homolog 2 Protein / analysis
  • Enhancer of Zeste Homolog 2 Protein / biosynthesis
  • Female
  • Humans
  • Immunohistochemistry
  • Isoenzymes / analysis
  • Isoenzymes / biosynthesis
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / biosynthesis
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Retinal Dehydrogenase / analysis
  • Retinal Dehydrogenase / biosynthesis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Ki-67 Antigen
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein