title: Antiapoptotic Bcl-2 family protein expression increases with progression of oligodendroglioma.
abstract: BACKGROUND
  Altered expression of Bcl-2 family proteins has been associated with tumorigenesis and tumor progression as well as resistance to radiotherapy and chemotherapy. In the current study, Bcl-2 family protein expression was examined in oligodendrogliomas and anaplastic oligodendrogliomas, and an attempt was made to determine whether these proteins accumulate during disease progression and to search for protein expression patterns predictive of time to progression and overall survival.
  
  
  METHODS
  A total of 42 oligodendroglioma tissue samples, 26 de novo World Health Organization (WHO) Grade 2 oligodendrogliomas, and 16 de novo WHO Grade 3 anaplastic oligodendrogliomas were studied. Nineteen Grade 2 tumors progressed: 10 again were Grade 2 oligodendrogliomas and 8 had progressed to higher grade lesions. Eight anaplastic oligodendrogliomas progressed: five again were WHO Grade 3 tumors and three were glioblastoma multiforme. Expression of Bcl-2, Bax, Bcl-X, and Mcl-1 proteins and of the proliferation marker Ki-67 was evaluated by immunohistochemistry. Apoptotic cells were quantified by in situ nick translation (ISNT).
  
  
  RESULTS
  De novo WHO Grade 2 oligodendrogliomas had higher Bcl-2 scores (P = 0.037), lower MIB-1 scores (P = 0.0012), and lower ISNT scores (P = 0.049) compared with de novo WHO Grade 3 anaplastic oligodendrogliomas. In de novo oligodendrogliomas, low numbers of Bax positive cells were associated with a short time to disease progression (P = 0.043). In de novo anaplastic oligodendrogliomas, low numbers of Bcl-2 positive cells correlated with short survival (P = 0.029). In tumors that had progressed from WHO Grade 3 anaplastic oligodendrogliomas, the authors found significantly more Bcl-X positive (P = 0.005), Mcl-1 positive (P = 0.002), and Bax positive (P = 0.03) cells.
  
  
  CONCLUSIONS
  The results of the current study show that progression of oligodendrogliomas and anaplastic oligodendrogliomas is associated with an enhanced expression of antiapoptotic Bcl-2 family proteins.
authors.affiliation: Institute of Brain Research, University of Tübingen Medical School, Tübingen, Germany.
authors.forename: M H
authors.initials: MH
authors.lastname: Deininger
authors.forename: M
authors.initials: M
authors.lastname: Weller
authors.forename: J
authors.initials: J
authors.lastname: Streffer
authors.forename: R
authors.initials: R
authors.lastname: Meyermann
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009837:Oligodendroglioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D019394:Ki-67 Antigen; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein