Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin's lymphomas

Hum Pathol. 2007 Jan;38(1):103-13. doi: 10.1016/j.humpath.2006.06.017. Epub 2006 Sep 1.

Abstract

The expression of various bcl2 family proteins has been reported in Hodgkin and Reed-Sternberg cells, but the proteins bad, bid, and bim have not been analyzed in classical Hodgkin's lymphomas (HLs). This study aimed to investigate the expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, bim, and active caspase 3, and the TUNEL (terminal deoxynucleotidyl transferase-mediated in situ labeling) index to gain further insight into the apoptosis profile of classical HLs. A high expression of the proteins bcl2, bcl-xl, mcl1, bax, bak, bad, bid, and bim in HRS cells was found in 27 of 101 (27%), 95 of 101 (94%), 27 of 97 (29%), 73 of 95 (77%), 37 of 102 (36%), 85 of 94 (90%), 19 of 109 (17%), and 43 of 91 (47%) cases, respectively. The high expression of bcl-xl, bax, and bad in HRS cells in most classical HLs indicates that these proteins may play predominant roles in the regulation of apoptosis in classical HLs. Active caspase 3-positive and TUNEL-positive Reed-Sternberg cells were detected in 47 of 70 (67%; range, 0%-12%) and 60 of 71 (85%; range, 0%-19%) cases, respectively. Significant positive correlations were found between bax/bcl2 (P = .002), bad/bcl2 (P = .020), bad/bcl-xl (P = .003), and bim/mcl1 (P = .036). Based on these findings, it could be hypothesized that the antiapoptotic proteins bcl2, bcl-xl, and mcl1 may counteract the expression of the proapoptotic proteins bax, bad, and bim, thereby contributing to the survival of Reed-Sternberg cells.

MeSH terms

  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / analysis
  • BH3 Interacting Domain Death Agonist Protein / analysis
  • Bcl-2-Like Protein 11
  • Caspase 3 / biosynthesis*
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology*
  • Hodgkin Disease / physiopathology
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Membrane Proteins / analysis
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins / analysis
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Reed-Sternberg Cells / chemistry
  • Reed-Sternberg Cells / pathology
  • bcl-2 Homologous Antagonist-Killer Protein / analysis
  • bcl-2-Associated X Protein / analysis
  • bcl-Associated Death Protein / analysis
  • bcl-X Protein / analysis

Substances

  • Apoptosis Regulatory Proteins
  • BAD protein, human
  • BAK1 protein, human
  • BAX protein, human
  • BCL2L11 protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Bcl-2-Like Protein 11
  • Membrane Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Caspase 3