Consistent nuclear expression of thyroid transcription factor 1 in subependymal giant cell astrocytomas suggests lineage-restricted histogenesis

Clin Neuropathol. 2015 May-Jun;34(3):128-31. doi: 10.5414/NP300818.

Abstract

Thyroid transcription factor 1 (TTF-1) is encoded by the NKX2-1 homeobox gene. Besides specifying thyroid and pulmonary organogenesis, it is also temporarily expressed during embryonic development of the ventral forebrain. We recently observed widespread immunoreactivity for TTF-1 in a case of subependymal giant cell astrocytoma (SEGA, WHO grade I)--a defining lesion of the tuberous sclerosis complex (TSC). This prompted us to investigate additional SEGAs in this regard. We found tumor cells in all 7 specimens analyzed to be TTF-1 positive. In contrast, we did not find TTF-1 immunoreactivity in a cortical tuber or two renal angiomyolipomas resected from TSC patients. We propose our finding of consistent TTF-1 expression in SEGAs to indicate lineage-committed derivation of these tumors from a regionally specified cell of origin. The medial ganglionic eminence, ventral septal region, and preoptic area of the developing brain may represent candidates for the origin of SEGAs. Such lineage-restricted histogenesis may also explain the stereotypic distribution of SEGAs along the caudate nucleus in the lateral ventricles.

MeSH terms

  • Adolescent
  • Adult
  • Astrocytoma / metabolism
  • Astrocytoma / pathology*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Nucleus / metabolism
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / biosynthesis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Transcription Factors
  • Young Adult

Substances

  • DNA-Binding Proteins
  • TTF1 protein, human
  • Transcription Factors