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ORIGINAL ARTICLE
Year : 2010  |  Volume : 47  |  Issue : 4  |  Page : 412-417
 

Detection of B cell lymphoma 2, tumor protein 53, and FAS gene transcripts in blood cells of patients with breast cancer


1 Cancer Gene Therapy Laboratory, Shiraz Institute for Cancer Research, Shiraz, Iran
2 Immunotherapy Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
3 Cancer Gene Therapy Laboratory, Shiraz Institute for Cancer Research; Department of Surgery, Shiraz University of Medical Sciences, Shiraz, Iran
4 Cancer Gene Therapy Laboratory, Shiraz Institute for Cancer Research; Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

Date of Web Publication4-Dec-2010

Correspondence Address:
M Habibagahi
Immunotherapy Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz
Iran
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Source of Support: Iranian Cancer Network, Shiraz Institute and Shiraz University of Medical Sciences, Conflict of Interest: None


DOI: 10.4103/0019-509X.73576

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  Abstract 

Background: Proteins encoded by FAS, BCL-2 and TP53 genes are major regulators of cellular survival and apoptosis. Results of recent investigations show remarkable biological features of these factors, which propose their role in the course of cancer. Therefore, it is plausible to test whether transcripts of these genes could be detected in the peripheral blood cells of patients with breast cancer. Materials and Methods: Real-time polymerase chain reaction assay was performed to detect FAS, BCL-2, and TP53 gene transcripts in the peripheral blood samples of 50 women with histologically confirmed infiltrative ductal carcinoma of the breast. Gene expression of patients was compared with 40 healthy women without history of malignancies or autoimmune disorders. Results: The relative overexpression of BCL-2 in the blood cells from patients of early stages (I and II), nonmetastatic and low-grade tumors compared with healthy individuals, was shown by measuring the gene transcript. Similarly, 3-4-fold higher expression of FAS was found in those patients. The measurement of TP53 transcripts also showed higher levels of gene expression in patients compared with healthy controls. BCL-2 gene expression showed a significant correlation with FAS, while such a correlation was not observed between BCL-2 and TP53 . Conclusion: It seems tumor cells overexpress BCL-2 to inhibit apoptosis and guarantee their cell survival. As a physiologic response, FAS and TP53 could be upregulated to suppress tumors. However, these pathways at early stages of disease may be inadequate and cause progressive malignancy.


Keywords: BCL-2 , breast cancer, FAS, TP53


How to cite this article:
Jaberipour M, Habibagahi M, Hosseini A, Abbasi M, Sobhani-lari A, Talei A, Ghaderi A. Detection of B cell lymphoma 2, tumor protein 53, and FAS gene transcripts in blood cells of patients with breast cancer. Indian J Cancer 2010;47:412-7

How to cite this URL:
Jaberipour M, Habibagahi M, Hosseini A, Abbasi M, Sobhani-lari A, Talei A, Ghaderi A. Detection of B cell lymphoma 2, tumor protein 53, and FAS gene transcripts in blood cells of patients with breast cancer. Indian J Cancer [serial online] 2010 [cited 2019 Aug 26];47:412-7. Available from: http://www.indianjcancer.com/text.asp?2010/47/4/412/73576



  Introduction Top


Several mechanisms and multiple genes share to control cellular proliferation, growth, and apoptosis. The literature shows the importance of some pathways where expression of BCL-2, FAS, and p53 have major roles in their action.

FAS gene encodes the FAS protein, which is a member of the tumor necrosis factor superfamily and mediates apoptosis when cross-linked with FAS ligand (FASL) or agonistic anti-FAS antibody. [1] FAS-mediated apoptosis has been shown in several inflammatory diseases, autoimmune diseases, and cancers. [2],[3] Concentration of serum soluble form of FAS was shown to be associated with tumor progression and metastasis in patients. In this regard, the concentration of soluble FAS in serum has been suggested as a valuable prognostic factor in patients with breast cancer (BC). [4],[5]

BCL2 gene encodes the Bcl-2 protein, which blocks apoptosis mediated by physiologic stimuli or by multiple stress conditions. [6] Several studies have evaluated the overexpression of BCL-2 in BC patients, and have considered that as an independent prognostic marker. [7],[8],[9] Recently, it was shown that BCL-2 expression is highly associated with an increased risk of local recurrence in patients with early stage of BC and it might be useful to select optimal treatment options for these patients. [10]

TP53 encodes a phosphoprotein, which is a multifunctional transcription factor involved in the control of cell cycle, DNA repair after damage, and in apoptosis. [11] TP53 overexpression has been identified in 50-75% of BC cases, a frequency which highlights this gene as a useful tumor marker. [12] A large number of studies have shown the correlation of TP53 overexpression with high histologic grade of tumor, negative hormonal status, and higher death rate. [13],[14],[15], [16] Also, it was suggested that the detection of TP53 mutations in plasma DNA can be a useful prognostic factor and an early marker of recurrence or distant metastasis in BC. [17]

Due to biological impact of BCL-2, TP53 , and FAS, this study aimed to compare the expression levels of these genes in blood samples of patients with BC and healthy women.


  Materials and Methods Top


The participants in this study were 50 women with histopathologically confirmed infiltrative ductal carcinoma of the breast. The patients were referred to our laboratory from breast clinics during July to December 2008. All the patients provided their informed consent to take part in the study and the study was approved by the ethical committee of the university. Peripheral venous blood samples (2 mL) were collected before any therapeutic intervention on the day of surgery by venipuncture, using ethylenediaminetetraacetic acid as anticoagulant. None of the patients had received chemotherapy, radiotherapy, or immunotherapy at the time of sampling. Blood samples from 40 healthy women without history of malignancies or autoimmune disorders were also obtained as controls. Mean ages of the patients and healthy controls were 50 years (range, 22-81) and 55 years (range, 24- 70), respectively.

Total RNA was prepared from blood cells after lysis with ammonium chloride and TRizol reagent (Invitrogen, Paisley, UK) treatment according to the manufacturer's instructions. The quantity and quality of the extracted RNA samples were estimated by spectrophotometry at 260 and 280 nm. RNA was treated with DNase I (Invitrogen- Gibco, Paisley, UK) before cDNA synthesis to avoid DNA contamination. Complementary DNA was synthesized from 5μg of total RNA using the RevertAid First Strand cDNA Synthesis Kit (Fermentase, Vilnius, Lithuania).

The abundance of FAS, BCL-2, and TP53 gene transcripts were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) using Bio-Rad Chromo 4 Real-time PCR Detector system (Bio-Rad, CA, USA) with Syber Green PCR Master Mix (Applied Biosystems, CA, USA) in triplicates. Expression of a β-actin housekeeping gene was used as a reference for the level of target gene expression. [Table 1] shows sequences of primer pairs for each gene.
Table 1: Forward and reverse primer sequences for PCR amplification

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PCR reactions were performed in a final volume of 25 μL and contained 0.5 μg of the cDNA product, 4.0 pmol of each primer, and 1Χ reaction mix consisting of FastStart DNA polymerase reaction buffer, dNTPs, and SYBR green I (Applied Biosystems, CA, USA).

Thermal cycling for all genes was initiated with a denaturation step at 95C for 10 min, followed by 30 cycles (denaturation at 95C for15 s, annealing at 60C for 30 s, and elongation at 60C for 34 s, when fluorescence appeared). The qRT-PCR amplification products were assessed by melting curve analysis and by electrophoresis on 1% agarose gel (data not shown).

For each target gene, the efficiency of the real-time PCR reaction was calculated from the slope of the standard curve. Standard curves were plotted by Ct values of serial dilutions of plasmids containing the genes of interest against the logarithm concentration of input template DNA. Accordingly, the efficiency of the FAS, BCL-2, and TP53 PCR reactions were calculated as 94%, 95.7%, and 97%, respectively. The relative amounts of FAS, BCL-2, and TP53 transcripts were determined from the ΔCt and 2 (−∆ct) formulas. Target-to-reference gene ratios were calculated with the Pfaffl method. [18]

The numbers of FAS, BCL-2, and TP53 transcripts in the peripheral blood were compared with the corresponding values from control samples with the nonparametric Mann-Whitney U test using SPSS software v. 11.5 (IL, USA). Graphs were plotted and analyzed using Prism 4 software (CA, USA).


  Results Top


The following parameters were obtained from the hospital records of the 50 patients: age, tumor size, tumor histology, lymph node metastases, clinical stage, histological grade, and presence of metastases. Tumor stage was determined with the tumor-node-metastasis classification. [Figure 1] summarizes the frequency of women with different clinical classifications.
Figure 1: The distribution of patients with breast cancer indifferent clinical criteria. The majority of studied patients showed nonmetastatic and low-grade tumor.

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Quantitative real-time PCR assay was used to detect and compare the expression of these genes in the peripheral blood cells of 50 patients and 40 healthy control women.

[Figure 1] shows significantly higher expression of FAS in patients compared with healthy control women (P = 0.0178). Among patients in the early stages of the disease (stage I-II), the relative expression level of FAS was about 3-fold as high as in the control group (P = 0.0043). Similarly, FAS expression in patients with the diagnosis of nonmetastatic and low-grade tumors showed up to 4- and 3-fold increases, respectively [P =0.019, [Figure 2]]. Due to limited numbers of patients with high-grade tumor, comparison of FAS gene expression between groups of patients was not possible although less FAS gene expression was detected in patients with higher grade of tumor.
Figure 2: Median expression levels of FAS transcript in the peripheral blood cells of breast cancer (BC) patients and healthy controls. Data were calculated with the 2(−Δct) formula and analyzed with the nonparametric two-tailed Mann-Whitney U test. Significant differences were found in the levels of FAS expression between total, nonmetastatic, early-stage (I, II), and low-grade BC patients and normal controls (P = 0.0178, P = 0.0047, P = 0.0043, and P = 0.019, respectively).

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Real-time PCR results showed significantly higher expression of BCL-2 in patients compared with healthy women (P = 0.0045). The greatest difference appeared in patients of stages I and II, in whom relative expression (target-to-reference gene ratio) was 2.89 vs 0.19 in the control group (P = 0.0025). Women with nonmetastatic and low-grade BC also had higher BCL-2 expression than healthy women [P = 0.0157 and P = 0.0248, respectively; [Figure 3]]. Significant overexpression of BCL-2 was also found in metastatic patients compared with the nonmetastatic group (P = 0.0381). However, no significant difference was found between the expression of BCL-2 in patients with low-grade and high-grade tumors.
Figure 3: Median expression levels of BCL-2 transcript in the peripheral blood cells of breast cancer (BC) patients and healthy controls. Calculations were performed as explained in Figure 1. Significant differences were found in the levels of BCL-2 expression between total, nonmetastatic, early-stage (I, II), and low-grade BC patients and normal controls (P = 0.0045, P = 0.0157, P = 0.0025, and P = 0.0248, respectively)

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Comparison of TP53 gene expression in the patients and healthy controls showed up to 10-fold increase of gene expression in patients (P = 0.0068). The patients in early stages of the disease showed a significant increase in the mean relative TP53 gene expression (P = 0.0018). Increased expression of TP53 was also found in nonmetastatic patients (P = 0.009) and those with a low-grade tumor burden (P = 0.0012) [Figure 4]. Interestingly, when TP53 expression was compared between low-grade and high-grade patients, significantly more TP53 gene transcripts were detected in blood cells of patients with low-grade BC (P = 0.0004). In addition, the patients of stages I and II of the disease showed significantly higher expression of TP53 transcripts than late-stage patients (P = 0.018).
Figure 4: Median expression levels of TP53 transcript in the peripheral blood cells of breast cancer (BC) patients and healthy controls. Calculations were performed as explained in Figure 1. Significant differences were found in levels of TP53 expression between total, nonmetastatic, early-stage (I, II), and low-grade BC patients and normal controls (P = 0.0068, P = 0.009, P = 0.0018, and P = 0.0012, respectively)

Click here to view


Comparing expression levels of the genes showed a significant correlation between BCL-2 and FAS (r = 0.518, P = 0.001) and between TP53 and FAS (r = 0.318, P = 0.023). However, there was not such association between BCL-2 level and TP53 expression (r = 0.153, P = 0.281) (data not shown).


  Discussion Top


There has been great advancement in the early detection of circulating tumor cells with new sensitive techniques. These methods use different markers to identify rare tumor cells in the blood circulation. [19],[20],[21] However, we sought to analyze other endogenous markers in blood circulation rather than those from tumor cells in patients with early stages of BC. In this regard, we found the overexpression of BCL-2, TP53, and FAS in the peripheral blood cells from women in early stages of BC in comparison with healthy subjects. Interestingly, the relative expression of these genes in patients with nonmetastatic and low-grade tumor was significantly higher than healthy controls.

FAS is an apoptotic factor that activates a cascade reaction of caspases and thus perpetuates the process of apoptosis. [22] Several studies on BC patients have indicated that FAS can be regarded as an informative prognostic marker, [23] although their conclusions are still debatable. A significant association of FAS and FASL expression with tumor stage of patients has been shown previously. [5] Moreover, data show that FAS expression could contribute to the generation and progression of BC, and the levels of expression of FAS were in correlation with metastasis of tumor into the axillary lymph nodes. [24] The results of another study of 108 patients with BC of stages I or II showed a significant association between the expression of FAS and the number of tumor recurrences and also lymph node metastasis. [25] Our data also showed that BC patients in early stages of the disease (I and II) had significantly higher levels of FAS transcripts than healthy women. However, in a study by Sjostrom-Mattson et al, on 59 patients with BC, the similarity between primary breast tumors and matching metastasis lymph nodes was examined and showed dissimilar expression of p53, bax, bcl-2 , FAS, and FASL in those lymph nodes. [26] On the other hand, studies by Puiu et al, elegantly showed the similarity between the ratio of the corresponding mRNA species of transmembrane vs soluble FAS isoforms in patients with breast cancer. [27] Accordingly, the prevention of FAS-mediated apoptosis in cancer cells, such as breast tumors, cannot entirely be explained by the possible changes in FAS expression, and hence other mechanisms should be investigated. Future studies should resolve the variations among results that exist about the expression of this proapoptotic marker.

Cell survival and apoptosis is a tightly regulated mechanism, which is controlled by multiple genes and BCL-2 is a major component of that. The overexpression of BCL-2 has been found in a variety of human tumors and lymphomas, where it acts as an oncogene protein. [28],[29] Several cross-sectional and meta-analysis studies verify BCL-2 as a favorable independent prognostic biomarker in BC. [30] A recent study by Yang et al showed that BCL-2 expression is highly associated with increased risk of local recurrence in patients with early stage of BC. [31] However, some other data indicate that a high Bcl-2 expression by tumor cells had no predictive value in BC patients. [32] More variations have been shown in serum content of bcl-2. In this regard, Andalib et al suggested the use of mRNA level rather than soluble form. [33] In this study, we measured the BCL-2 mRNA content in the peripheral blood of patients and found higher levels of the transcripts from patients with early stages of BC than in healthy women. The ease of such measurement may provide the opportunity to test more patients of different stages for a conclusive result.

TP53 has often been found disabled in cancer cells because of point mutation or gene deletion. [34] Different studies on patients with BC have shown the overexpression of TP53 by cancer cells and have regarded that as a significant prognostic marker. [35],[36] In a study by Gerson et al on patients of early stages of BC, Her-2 , estrogen receptor , and progesterone receptor - (triple-negative tumor cells) showed high frequency of TP53 expression. [37] Despite all these evidence, the contribution of this tumor suppressor in BC has been difficult to evaluate. [38] Our data indicating overexpression of TP53 in peripheral blood cells of patients of early-stage, low-grade, and nonmetastatic BC may provide more support regarding the possible role of this marker in BC detection.

Putting all these data together, it could be suggested that tumor cells at the early stages of BC overexpress BCL-2 to secure their outgrowth and survival. However, this coincides with the activation of a collection of physiologic regulatory mechanisms, such as increased expression of TP53 and FAS, which try to stop tumor cells by inducing apoptosis. Outcompeting or inadequate actions of these mechanisms result in tumor progression and malignancy. However, more data of other immunologic conditions are necessary to examine this suggestion and to test the specificity of these changes for BC.


  Acknowledgments Top


This work was funded by a grant from, Iranian Cancer Network, Shiraz Institute for Cancer Research (ICR-87-505) and Shiraz University of Medical Sciences (Grant No.87-4331). We also are grateful to the patients and healthy women who participated in this project.

 
  References Top

1.Bebenek M, Dus D, Kozlak J. FAS/FAS-ligand expressions in primary breast cancer are significant predictors of its skeletal spread. Anticancer Res 2007;27:215-8.  Back to cited text no. 1
    
2.Kawakami A, Eguchi K. Involvement of apoptotic cell death in autoimmune diseases. Med Electron Microsc 2002;35:1-8.  Back to cited text no. 2
    
3.Mitsiades CS, Poulaki V, Fanourakis G, Sozopoulos E, McMillin D, Wen Z, et al. FAS signaling in thyroid carcinomas is diverted from apoptosis to proliferation. Clin Cancer Res 2006;12:3705-12.  Back to cited text no. 3
    
4.Bewick M, Conlon M, Parissenti AM, Lee H, Zhang L, Gluck S, et al. Soluble FAS (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. J Hematother Stem Cell Res 2001;10:759-68.  Back to cited text no. 4
    
5.Zhang B, Sun T, Xue L, Han X, Zhang B, Lu N, et al. Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer. Carcinogenesis 2007;28:1067-73.  Back to cited text no. 5
    
6.Coultas L, Strasser A. The role of the Bcl-2 protein family in cancer. Semin Cancer Biol 2003;13:115-23.  Back to cited text no. 6
    
7.Thomadaki H, Scorilas A. Molecular profile of the BCL-2 family of the apoptosis related genes in breast cancer cells after treatment with cytotoxic/cytostatic drugs. Connect Tissue Res 2008;49:261-4.  Back to cited text no. 7
    
8.Kyndi M, Sorensen FB, Knudsen H, Alsner J, Overgaard M, Nielsen HM, et al. Impact of BCL-2 and p53 on postmastectomy radiotherapy response in high-risk breast cancer: A subgroup analysis of DBCG82 b&c. Acta Oncol 2008;47:608-17.  Back to cited text no. 8
    
9.Callagy GM, Webber MJ, Pharoah PD, Caldas C. Meta-analysis confirms BCL-2 is an independent prognostic marker in breast cancer. BMC Cancer 2008;8:153.  Back to cited text no. 9
    
10.Yang Q, Moran MS, Haffty BG. Bcl-2 expression predicts local relapse for early-stage breast cancer receiving conserving surgery and radiotherapy. Breast Cancer Res Treat 2009;115:343-8.  Back to cited text no. 10
    
11.Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991;351:453-6.  Back to cited text no. 11
    
12.Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53.  Back to cited text no. 12
    
13.Elledge RM, Allred DC. Prognostic and predictive value of p53 and p21 in breast cancer. Breast Cancer Res Treat 1998;52:79-98.  Back to cited text no. 13
    
14.Beenken SW, Grizzle WE, Crowe DR, Conner MG, Weiss HL, Sellers MT, et al. Molecular biomarkers for breast cancer prognosis: Coexpression of c-erbB-2 and p53. Ann Surg 2001;233:630-8.  Back to cited text no. 14
    
15.Jansen RL, Joosten-Achjanie SR, Volovics A, Arends JW, Hupperets PS, Hillen HF, et al. Relevance of the expression of bcl-2 in combination with p53 as a prognostic factor in breast cancer. Anticancer Res 1998;18:4455-62.  Back to cited text no. 15
    
16.Chae BJ, Bae JS, Lee A, Park WC, Seo YJ, Song BJ, et al. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn J Clin Oncol 2009;39:217-24.  Back to cited text no. 16
    
17.Di GH, Liu G, Wu J, Shen ZZ, Shao ZM. [Peripheral blood mutated p53 DNA and its clinical value in human breast cancer]. Zhonghua Zhong Liu Za Zhi 2003;25:137-40.  Back to cited text no. 17
    
18.Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001;29:e45.  Back to cited text no. 18
    
19.Beiske K, Burchill SA, Cheung IY, Hiyama E, Seeger RC, Cohn SL, et al. Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: Recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer 2009;100:1627-37.  Back to cited text no. 19
    
20.Martin M, Garcia-Saenz JA, Maestro De las Casas ML, Vidaurreta M, Puente J, Veganzones S, et al. Circulating tumor cells in metastatic breast cancer: Timing of blood extraction for analysis. Anticancer Res 2009;29:4185-7.  Back to cited text no. 20
    
21.Schmitt M, Foekens JA. Circulating tumor cells in blood of primary breast cancer patients assessed by a novel RT-PCR test kit and comparison with status of bone marrow-disseminated tumor cells. Breast Cancer Res 2009;11:109.  Back to cited text no. 21
    
22.Nagata S. Apoptosis by death factor. Cell 1997;88:355-65.  Back to cited text no. 22
    
23.Yakirevich E, Maroun L, Cohen O, Izhak OB, Rennert G, Resnick MB. Apoptosis, proliferation, and FAS (APO-1, CD95)/FAS ligand expression in medullary carcinoma of the breast. J Pathol 2000;192:166-73.  Back to cited text no. 23
    
24.Bi Y, Wei L, Mao HT, Zhang L, Zuo WS. [Expressions of FAS, CTLA-4 and RhoBTB2 genes in breast carcinoma and their relationship with clinicopathological factors]. Zhonghua Zhong Liu Za Zhi 2008;30:749-53.  Back to cited text no. 24
    
25.Bebenek M, Dus D, Kozlak J. FAS and FAS ligand as prognostic factors in human breast carcinoma. Med Sci Monit 2006;12:CR457-61.  Back to cited text no. 25
    
26.Sjostrom-Mattson J, von Boguslawski K, Bengtsson NO, Mjaaland I, Salmenkivi K, Blomqvist C. The expression of p53, bcl-2, bax, FAS and FASL in the primary tumour and lymph node metastases of breast cancer. Acta Oncol 2009;1-7. In press  Back to cited text no. 26
    
27.Puiu L, Petrakou E, Apostolidou A, Athanassiadou A, Psiouri L, Papachatzopoulou A, et al. Lack of FAS (APO-1/CD95) gene structural alterations or transcript variant ratio changes in breast cancer. Cancer Lett 2003;194:91-7.  Back to cited text no. 27
    
28.McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992;52:6940-4.  Back to cited text no. 28
    
29.Pietenpol JA, Papadopoulos N, Markowitz S, Willson JK, Kinzler KW, Vogelstein B. Paradoxical inhibition of solid tumor cell growth by BCL-2. Cancer Res 1994;54:3714-7.  Back to cited text no. 29
    
30.Callagy GM, Pharoah PD, Pinder SE, Hsu FD, Nielsen TO, Ragaz J, et al. Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index. Clin Cancer Res 2006;12:2468-75.  Back to cited text no. 30
    
31.Yang Q, Moran MS, Haffty BG. Bcl-2 expression predicts local relapse for early-stage breast cancer receiving conserving surgery and radiotherapy. Breast Cancer Res Treat 2009;115:343-8.  Back to cited text no. 31
    
32.Vargas-Roig LM, Cuello-Carrion FD, Fernandez-Escobar N, Daguerre P, Leuzzi M, Ibarra J, et al. Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant anthracycline based chemotherapy. Mol Oncol 2008;2:102-11.  Back to cited text no. 32
    
33.Alireza A, Raheleh S, Abbass R, Mojgan M, Mohamadreza M, Gholamreza M, et al. An immunohistochemistry study of tissue bcl-2 expression and its serum levels in breast cancer patients. Ann N Y Acad Sci 2008;1138:114-20.  Back to cited text no. 33
    
34.Kiaris H, Chatzistamou I, Trimis G, Frangou-Plemmenou M, Pafiti-Kondi A, Kalofoutis A. Evidence for nonautonomous effect of p53 tumor suppressor in carcinogenesis. Cancer Res 2005;65:1627-30.  Back to cited text no. 34
    
35.Pharoah PD, Day NE, Caldas C. Somatic mutations in the p53 gene and prognosis in breast cancer: A meta-analysis. Br J Cancer 1999;80:1968-73.  Back to cited text no. 35
    
36.Yamashita H, Nishio M, Toyama T, Sugiura H, Zhang Z, Kobayashi S, et al. Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. Breast Cancer Res 2004;6:R24-30.  Back to cited text no. 36
    
37.Gerson R, Alban F, Villalobos A, Serrano A. [Recurrence and survival rates among early breast cancer cases with triple negative immunophenotype]. Gac Med Mex 2008;144:27-34.  Back to cited text no. 37
    
38.Lacroix M, Toillon RA, Leclercq G. p53 and breast cancer, an update. Endocr Relat Cancer 2006;13:293-325.  Back to cited text no. 38
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]

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