p53 and bcl-2 in Epithelial Ovarian Carcinoma: Their Value as Prognostic Indicators at a Median Follow-up of 60 Months

Geisler, John P.; Geisler, Hans; Miller, Greg A.; Wiemann, Michael C.; Zhou, Zijie; Crabtree, William N.

doi:10.1006/gyno.2000.5780

Cited by 48 publications

(47 citation statements)

References 20 publications

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“…Conversely, Bcl-2 expression was correlated with poor prognosis in the study performed by Mano et al [22]. In this study, no significant correlation between Bcl-2 expression and OS was found, similar to previous studies [20,24]. This may be due to the number of patients with high expression level (17/83) was significantly lower than the number of the patients with low expression level (66/83).…”

Section: Discussionsupporting

confidence: 87%

“…Additional conflicting results from several clinical studies have been reported. While Tai et al reported higher rates of complete remission in patients with (H) Bax expression, Geisler et al observed the negative effect of Bcl-2 protein expression on prognosis [24,31]. However, it was reported that high Bax expression had a negative effect on complete remission rates in a recent clinical study [32].…”

Section: Discussionmentioning

confidence: 99%

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The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma

Yiğit¹,

Demir²,

Mo³

et al. 2012

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The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and antiBax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted.Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003).Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome. Key words: Bax, Bcl-2, ovarian cancer, platinum sensitivity, lymphocyte infiltrateEpithelial ovarian cancer is the most common cause of death among women with gynecologic cancer and the fifth leading cause of cancer deaths in all women [1]. In ovarian cancer, the prognostic factors can be divided into three groups: patient factors, tumor factors and treatment factors. Age and performance status are important patient factors that significantly influence the survival rate. Tumor factors such as the stage, histopathological findings, histologic grade and expression of cancer-related genes, also significantly affect survival. The residual tumor size, post-operative CA 125 level and the chemotherapeutic regimen, are important treatment factors for prognosis [2].The Bcl-2 family is a growing family of genes, which plays a major role in the regulation of cell suicide, acting either as inhibitors (e.g., Bcl-2, bcl-x1, mcl-1) or promoters (e.g., Bclxs, Bax, bak, bad) of apoptosis [3]. Expression of Bcl-2, the major inhibitor of apoptosis, is connected with parameters of favorable prognosis and prolonged survival in breast cancer; however in ovarian cancer the results are conflicting [4,5]. The Bcl-2 interacting protein, Bax, is a proapoptotic member of Bcl-2 family and is the main antagonist of Bcl-2. Bax expression, in contrast to Bcl-2 expression, was associated with an unfavorable outcome as well as with negative histopathological features [6]. Tumor-infiltrating lymphocytes (TILs) occur as a host response to several types of human carcinomas [7]. Several studies have evaluated the impact of T-lymphocyte infiltration on prognosis in ovarian cancer [8][9][10][11][12][13]. The presence of TILs (especially ...

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma

Yiğit¹,

Demir²,

Mo³

et al. 2012

neo

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“…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%

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

et al. 2003

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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.

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“…We observed increased expression of the prosurvival protein BAG-3 in platinumresistant ovarian cancer cells. 6 We therefore sought to determine the expression pattern of the BAG family of proteins and associated partners to discern relationships of these proteins with clinical features of aggressiveness in ovarian cancer.…”

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confidence: 99%

“…The Bcl-2 family and associated proteins have been implicated in the pathogenesis of ovarian cancer (3 -5). Bcl-xL and Bcl-2 may have prognostic importance in ovarian cancer (6,7). The BAG proteins act as cochaperones for Bcl-2 and Hsp70 (8,9).…”

mentioning

confidence: 99%

BAG-4/SODD and Associated Antiapoptotic Proteins Are Linked to Aggressiveness of Epithelial Ovarian Cancer

Annunziata¹,

Kleinberg

Davidson

et al. 2007

Clinical Cancer Research

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Purpose: We hypothesized that elevated expression in ovarian cancer of the BAG family of prosurvival proteins and associated partners would be associated with clinical features of aggressiveness in ovarian cancer. Experimental Design: Expression patterns of BAG-1, BAG-3, BAG-4, and Bcl-xL were determined by immunohistochemical analysis of tissue samples obtained at diagnosis from 28 women with stage III or stage IV ovarian cancer treated with cisplatin, paclitaxel, and cyclophosphamide after initial cytoreduction. Association of these proteins, BAG-6, heat shock protein 70 (Hsp70), Hsp27, and Bcl-2, with clinical variables was tested in ovarian cancer tissue arrays from Gynecologic Oncology Group tissue bank. Results: A statistically significant relationship was found between elevated cytoplasmic expression of BAG-4 and improved overall (P = 0.0002) and progression-free survival (P = 0.003) in the prospectively collected samples. Bcl-2 staining was significantly more frequent on the tissue array in lower stage (P = 0.005) and grade (P = 0.0009) tumors, whereas Hsp70 was prominent in higher grade cases (P = 0.002). Furthermore, Bcl-xL was more closely associated with serous compared with endometrioid ovarian cancers (P = 0.004). Conclusion: Unexpectedly, cytoplasmic expression of BAG-4 and Bcl-2 marked less aggressive ovarian cancer, whereas nuclear Hsp70 suggested more aggressive behavior. Bcl-xL may play a more prominent function in the pathology of serous histology ovarian cancers compared with the endometrioid subtype. The findings presented here support involvement of these proteins in the propagation of ovarian cancer and provide a basis for the development of molecular therapeutics modulating these survival pathways.

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p53 and bcl-2 in Epithelial Ovarian Carcinoma: Their Value as Prognostic Indicators at a Median Follow-up of 60 Months

Cited by 48 publications

References 20 publications

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma

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

BAG-4/SODD and Associated Antiapoptotic Proteins Are Linked to Aggressiveness of Epithelial Ovarian Cancer

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