title: Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer.
abstract: OBJECTIVE
  The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-X(L), and Mcl-1 in advanced ovarian cancer.
  
  
  METHODS
  Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-X(L) and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis.
  
  
  RESULTS
  Sixty-six percent of cancer cases expressed Bax, 62% Bcl-X(L), and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P: =.016) and less residual disease after surgery (P <.0001). In univariate analysis, Bax expression was associated with improved (P =.0004) prognosis and Mcl-1 expression with poorer (P =.011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P =.0115), together with residual disease status (P =.0016), differentiation grade (P =.0014), and the presence of ascites (P =.0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients' expression data for p53, Bax, and Bcl-2 with their residual disease status (P <.00001). None of the factors studied was able to predict response to chemotherapy.
  
  
  CONCLUSIONS
  The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.
authors.affiliation: Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo, Norway.
authors.forename: M
authors.initials: M
authors.lastname: Baekelandt
authors.forename: R
authors.initials: R
authors.lastname: Holm
authors.forename: J M
authors.initials: JM
authors.lastname: Nesland
authors.forename: C G
authors.initials: CG
authors.lastname: Tropé
authors.forename: G B
authors.initials: GB
authors.lastname: Kristensen
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D016019:Survival Analysis; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; 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