Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer.
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.
Baekelandt
M
M
Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo, Norway.
Holm
R
R
Nesland
J M
JM
Tropé
C G
CG
Kristensen
G B
GB
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
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