Clinical significance of apoptosis-related factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer.
OBJECTIVE
To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer.


METHODS
Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined.


RESULTS
Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival.


CONCLUSIONS
p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.
Baekelandt
M
M
Departments of Gynecologic Oncology and Pathology, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
Kristensen
G B
GB
Nesland
J M
JM
Tropé
C G
CG
Holm
R
R
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2