Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas

J Neuropathol Exp Neurol. 2010 Feb;69(2):129-38. doi: 10.1097/NEN.0b013e3181ca4767.

Abstract

PROX1 is a prospero-related transcription factor that plays a critical role in the development of various organs including the mammalian lymphatic and central nervous systems; it controls cell proliferation and differentiation through different transcription pathwaysand has both oncogenic and tumor-suppressive functions. We investigated PROX1 expression patterns in 56 human astrocytic gliomas of different grades using immunohistochemistry. An average of 79% of cells in World Health Organization Grade IV (glioblastoma, n = 15) and 57% of cells in World Health Organization Grade III (anaplastic astrocytoma, n = 13) were strongly PROX1 positive; low-grade diffuse astrocytomas (Grade II, n = 13) had 21% of cells that were strongly positive; Grade I tumors (n = 15) had 1.5%; and non-neoplastic brain tissue (n = 15) had 3.7% of cells that were PROX1 positive. Double immunolabeling showed that PROX1+ cells in glioblastomas frequently coexpressed early neuronal proteins MAP2 and betaIII-tubulin but not the mature neuronal marker protein NeuN. Analyses of coexpression with proliferation markers suggest that PROX1+ cells have a marginally lower rate of proliferation than other tumor cells but are still mitotically active. We conclude that PROX1 may constitute a useful tool for the diagnosis and grading ofastrocytic gliomas and for distinguishing Grade III and Grade IV tumors from Grade I and Grade II tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear / metabolism
  • Astrocytoma / blood supply
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology*
  • Biomarkers / metabolism
  • Brain Diseases / metabolism
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • Cell Proliferation
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Microtubule-Associated Proteins / metabolism
  • Microvessels / metabolism
  • Mitosis
  • Nerve Tissue Proteins / metabolism
  • Tubulin / metabolism
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antigens, Nuclear
  • Biomarkers
  • Homeodomain Proteins
  • MAP2 protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Tubulin
  • Tumor Suppressor Proteins
  • neuronal nuclear antigen NeuN, human
  • prospero-related homeobox 1 protein