title: Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases.
abstract: OBJECTIVE
  Dysregulation of genes that control apoptosis can contribute to tumor progression and increased drug resistance. The BCL2 gene and its family member BCL-x as well as the TP53 genes regulate apoptosis and have been shown to have a direct effect on the sensitivity of cancer cells to radiation and chemotherapeutic agents.
  
  
  METHODS
  The expression of BCL-x, a BCL2-related protein that is a potent inhibitor of apoptosis, was investigated by immunohistochemical and immunoblot methods in 43 primary untreated breast carcinomas, in conjunction with BCL2 and TP53.
  
  
  RESULTS
  BCL-x protein was overexpressed in 18 of 42 (43%) invasive breast cancers when compared with adjacent normal breast epithelium. Western blot analysis of eight primary breast cancers and five breast cancer cell lines indicated that BCL-xL was the predominant BCL-x protein expressed. Overexpression of BCL-x protein in these tumors was associated with higher tumor grade and increased number of positive nodes. In contrast, BCL2 protein was overexpressed in 19 of 42 tumors (45%) and was strongly correlated with estrogen receptor positivity, lower tumor grade, smaller tumor size, and lower stage. TP53 protein immunostaining was detected in 12 of 40 tumors (29%) and was inversely correlated with BCL2 expression and ER positivity. There was no correlation between the level of BCL-x protein expression and age, tumor size, ER status, and TP53 status. At a median follow-up time of 216 weeks, there was a trend toward decreased overall survival in patients with tumors overexpressing BCL-x.
  
  
  CONCLUSIONS
  These findings suggest that expression of BCL-x protein is increased in a significant fraction of invasive breast cancers. In contrast to BCL2 expression, up-regulation of BCL-x protein may be a marker of tumor progression. Additional data including larger numbers of patients, more uniform treatments, and longer follow-up are needed to define the prognostic significance of overexpression of BCL-x during breast cancer progression.
authors.affiliation: Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago 60637-1470, USA.
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: M O
authors.initials: MO
authors.lastname: Adeyanju
authors.forename: A R
authors.initials: AR
authors.lastname: Safa
authors.forename: F
authors.initials: F
authors.lastname: Hagos
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: W M
authors.initials: WM
authors.lastname: Recant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D005260:Female; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein