Expression of Apoptosis-Related Proteins Is an Independent Determinant of Patient Prognosis in Advanced Ovarian Cancer

Baekelandt, M.; Holm, Ruth; Nesland, Jahn M.; Tropé, Claes G.; Kristensen, Gunnar B.

doi:10.1200/jco.2000.18.22.3775

Cited by 65 publications

(58 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In subgroups related to the TP53 status, BCL-2 and BAX demonstrated an influence on CR or DFS, which was not seen in all tumours. Among other studies evaluating predictive significance of BCL-2 (Herod et al, 1996;Mano et al, 1999;Schuyer et al, 2001), including two published by Baekelandt et al (1999Baekelandt et al ( , 2000 on a comparable number of ovarian carcinomas, only Mano et al (1999) noticed higher frequency of CR in patients with BCL-2 negative tumours.…”

Section: Discussionmentioning

confidence: 90%

“…In regard to BAX expression, a few studies have addressed the issue of its clinical significance in advanced stage ovarian carcinomas; however, associations with CR or DFS have not been observed (Marx et al, 1997;Baekelandt et al, 2000;Sengupta et al, 2000;Schuyer et al, 2001). Recently, Schuyer et al (2001) found an association of BAX expression with progression-free survival.…”

Section: Discussionmentioning

confidence: 99%

“…The strong impact of clinical parameters on clinical end points in our analysis is in agreement with other studies (Makar et al, 1995;Partridge et al, 1996;Eisenhauer et al, 1999). Usually, immunohistochemical markers present lower associations with clinical end points than clinical parameters (Diebold et al, 1996;Herod et al, 1996;Baekelandt et al, 1999Baekelandt et al, , 2000Mano et al, 1999;Geisler et al, 2000;Reles et al, 2001;Schuyer et al, 2001). In our analysis, the only exception was the positive influence of high BAX expression on DFS in patients with TP53-positive ovarian carcinomas -it was stronger than that of the FIGO stage.…”

Section: Discussionmentioning

confidence: 99%

“…Analyses of TP53 and/or apoptosis proteins in large groups of ovarian carcinomas are rare (Hartmann et al, 1994;Eltabbakh et al, 1997;Marx et al, 1997;Baekelandt et al, 1999Baekelandt et al, , 2000Ferrandina et al, 1999). To our knowledge, MEK1 expression and its clinical significance have not been evaluated yet in ovarian carcinomas.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

et al. 2003

View full text Add to dashboard Cite

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatinbased chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB -IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P ¼ 0.005) or the only (in FIGO IIIC, P ¼ 0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(À) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P ¼ 0.047) and by BCL2 expression in the TP53(À) group (P ¼ 0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P ¼ 0.049); its loss was found with advancing FIGO stage (P ¼ 0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Patients with both BAX and BCL-2 positive tumours showed an even better survival compared to patients with BAX positive/BCL-2 negative tumours. A recent study, on 185 stage III ovarian cancer patients by Baekelandt et al (2000), also showed that in advanced ovarian cancer the combined apoptosis related protein BAX and BCL-2 expression data was of independent prognostic significance. One explanation for this unexpected observation could be that overexpression of BCL-2 was shown to increase the half-life of BAX, suggesting a feedback mechanism that may help to maintain the ration of BCL-2 to BAX protein in physiologically appropriate ranges .…”

Section: Discussionmentioning

confidence: 95%

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

Schuyer¹,

Burg²,

Henzen‐Logmans

et al. 2001

Br J Cancer

View full text Add to dashboard Cite

Summary Traditional clinicopathological features do not predict which patients will develop chemotherapy resistance. The TP53 gene is frequently altered in ovarian cancer but its prognostic implications are controversial. Little is known on the impact of TP53-downstream genes on prognosis. Using molecular and immunohistochemical analyses we examined TP53 and its downstream genes p21, BAX and BCL-2 in ovarian tumour tissues and have evaluated the results in relation to clinico-pathological parameters, clinical outcome and response to platinum-based chemotherapy. Associations of tested factors and patient and tumour characteristics were studied by Spearman rank correlation and Pearsons χ 2 test. The Cox proportional hazard model was used for univariate and multivariate analysis. The associations of tested factors with response was tested using logistic regression analysis. TP53 mutation, p21 and BCL-2 expression were not associated with increased rates of progression and death. Expression of TP53 was associated with a shorter overall survival only (relative hazard rate [RHR] 2.01, P = 0.03). Interestingly, when combining TP53 mutation and expression data, this resulted in an increased association with overall survival (P = 0.008). BAX expression was found to be associated with both progression-free (RHR 0.44, P = 0.05) and overall survival (RHR 0.42, P = 0.03). Those patients who simultaneously expressed BAX and BCL-2 had a longer progression-free and overall survival compared to patients whose tumours did not express BCL-2 (P = 0.05 and 0.015 respectively). No relations were observed between tested factors and response to platinum-based chemotherapy. We conclude that BAX expression may represent a prognostic indicator for patients with ovarian cancer and that the combined evaluation of BAX and BCL-2 may provide additional prognostic significance.

show abstract

A Phase II Study of the MDR Inhibitor Biricodar (INCEL, VX-710) and Paclitaxel in Women with Advanced Ovarian Cancer Refractory to Paclitaxel Therapy

Seiden

Swenerton

Matulonis

et al. 2002

Gynecologic Oncology

View full text Add to dashboard Cite

Expression of Apoptosis-Related Proteins Is an Independent Determinant of Patient Prognosis in Advanced Ovarian Cancer

Abstract: 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.

Cited by 65 publications

References 25 publications

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen

Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2

A Phase II Study of the MDR Inhibitor Biricodar (INCEL, VX-710) and Paclitaxel in Women with Advanced Ovarian Cancer Refractory to Paclitaxel Therapy

Contact Info

Product

Resources

About