title: Subependymal giant cell astrocytoma: a clinicopathological study of 23 cases with special emphasis on proliferative markers and expression of p53 and retinoblastoma gene proteins.
abstract: OBJECTIVE
  To gain a better insight into the biological behaviour of subependymal giant cell astrocytoma (SEGA), tumour suppressor gene protein expression and various proliferative indices were studied in these tumours and correlated with histological features and clinical outcome.
  
  
  METHODS
  We studied 23 cases of SEGA, 19 from our own Institute and four from the National Institute of Mental Health and Neurological Sciences (NIMHANS), Bangalore, India. Immunohistochemical staining for various glial and neuronal markers, proliferative markers (MIB-1, Topoisomerase II alpha PCNA) and tumour suppressor gene protein expression of p53 and retinoblastoma (Rb) were performed.
  
  
  RESULTS
  Nineteen cases of SEGA were collected over a period of 23 years (January 1978-December 2001), which accounted for 0.16% of all intracranial tumours and 0.51% of all gliomas reported at this centre. Ages ranged from 4 to 37 years (mean 13.2 years) with a male preponderance. Nine of the 23 cases were associated with tuberous sclerosis (TS), six at the time of diagnosis, while three developed TS during the follow-up period. Treatment consisted of surgical resection (total in nine cases and subtotal in 14 cases) followed by radiotherapy in seven cases. Except for two patients who died in the immediate post-operative period of surgical complications, the remaining patients were all alive in the follow-up period (mean 37.1 months). One patient experienced recurrence 22 years after the first surgery and a second patient after 2 years. Necrosis and/or mitoses were observed in five cases. Immunohistochemically, tumours were positive for both glial and neuronal markers. Interspersed inflammatory cells were a mixture of mast cells and lymphocytes of T immunophenotype. The MIB-1 labelling index (LI) ranged from 0 to 8% (mean 3.0%), topoisomerase II alpha (topo II alpha) LI from 0 to 9.5% (mean 2.9%) and PCNA LI from 10 to 59% (mean 32.5%). The difference in the labelling indices of tumours with and without mitoses and/or necrosis was not statistically significant. None of the tumours revealed loss of Rb gene protein expression. p53 immunopositivity was seen in 14 cases (labelling indices ranged from 1 to 7.3% with a mean of 2.4%). The correlation between the MIB-1 LI and topo II alpha LI, and topo II alpha LI and PCNA LI was significant (P<0.05) but not so with other parameters like p53 protein expression, duration of survival and morphological features such as mitoses and necrosis.
  
  
  CONCLUSIONS
  SEGAs are rare intraventricular tumours associated with TS and express both neuronal and glial markers. They have a low proliferative potential. Mitoses and necrosis are not associated with a worse prognosis. In view of the low proliferative indices and long survival of these patients without recurrence, the role of post-operative radiotherapy is questionable. These patients should be followed up closely as many of them develop stigmata of tuberous sclerosis at a later stage.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Mehar
authors.initials: M
authors.lastname: Sharma
authors.forename: Angela
authors.initials: A
authors.lastname: Ralte
authors.forename: Rina
authors.initials: R
authors.lastname: Arora
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
authors.forename: S K
authors.initials: SK
authors.lastname: Shankar
authors.forename: Chitra
authors.initials: C
authors.lastname: Sarkar
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002551:Cerebral Ventricle Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D014695:Cerebral Ventriculography; D002648:Child; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D018315:Glioma, Subependymal / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008938:Mitosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II