TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens

Ziółkowska-Seta, Izabela; Mądry, Radosław; Kraszewska, Ewa; Szymanska, T.; Timorek, Agnieszka; Rembiszewska, Alina; Kupryjańczyk, Jolanta

doi:10.1016/j.ygyno.2008.09.008

Cited by 22 publications

(19 citation statements)

References 36 publications

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“…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]. In our study, no relationship between platinum sensitivity and antiapoptotic Bcl-2 protein expression was demonstrated.…”

Section: Discussioncontrasting

confidence: 70%

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: Discussioncontrasting

confidence: 70%

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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“…Surrogate markers, such as serum levels of CA125,7 8 or molecules generally involved in cell proliferation9 and apoptotic10 pathways have been implicated as predictive markers for therapeutic response. However, the cellular mechanisms and molecules involved in taxane- or platinum-based action in proliferating cells, for example, microtubule proteins such as β-tubulin11 12 and/or DNA repair associated proteins such as BRCA113 or ERCC1,14 15 have only been addressed in few studies 16…”

Section: Introductionmentioning

confidence: 99%

Aurora-B protein expression is linked to initial response to taxane-based first-line chemotherapy in stage III ovarian carcinoma

Beussel

Hasenburg²,

Bogatyreva³

et al. 2011

J Clin Pathol

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“…As mutation in TP53 may cause its up-regulation, protein over-expression of p53 is frequently assessed [18-21]. This study performed immunohistochemistry to determine p53 up-regulation and defined p53 overexpression for strongly positive (IRS > 8) cases.…”

Section: Discussionmentioning

confidence: 99%

“…Up to now the mechanism leading to p53 up-regulation remains to be controversial [17]. Today, assessing p53 by immunohistochemistry instead of TP53 mutation analysis is a well-established method [18-21] and has been intensively studied [22,23]. However, it needs to be mentioned that so far p53 immunohistochemistry may not fully resemble TP53 mutation testing.…”

Section: Introductionmentioning

confidence: 99%

KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants

et al. 2013

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BackgroundPatients diagnosed for a serous ovarian borderline tumor (s-BOT) typically present with an excellent clinical outcome. However there have been controversies concerning the prognostic impact of so-called implants, an extra ovarian spread occurring alongside the s-BOT in certain cases. It remains obscure whether these implants actually resemble metastasis owning the same genetic pattern as the ovarian primary or whether they develop independently.MethodsThe current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16INK4a immunophenotype of s-BOTs and corresponding implants (n = 49) of 15 patients by pyro-sequencing and immunostaining, respectively.ResultsA significant proportion of both s-BOTs and implants showed KRAS or BRAF mutation and though p16INK4a was found to be abundantly expressed, p53 immunoreactivity was rather low. When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared no patient presented with a fully matching mutation profile of s-BOTs and all corresponding implants.ConclusionsThe current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. Hence, our findings may assist to explain the different clinical presentation of s-BOTs and implants and might encourage to applying more individualized follow up protocols.

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TP53, BCL-2 and BAX analysis in 199 ovarian cancer patients treated with taxane-platinum regimens

Cited by 22 publications

References 36 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

Aurora-B protein expression is linked to initial response to taxane-based first-line chemotherapy in stage III ovarian carcinoma

KRAS, BRAF genotyping reveals genetic heterogeneity of ovarian borderline tumors and associated implants

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