Overexpression of UQCRC2 is correlated with tumor progression and poor prognosis in colorectal cancer

Ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) is an important subunit of mitochondrial respiratory complex III. However, its role in tumorigenesis and tumor progression remains unknown, especially with regards to colorectal cancer (CRC). In this research, we measured the expression of UQCRC2 protein by immunohistochemistry assay in 89 paired paraffin-embedded tumor tissues and corresponding adjacent normal tissues from patients with colorectal adenocarcinoma and investigated possible correlations of UQCRC2 expression with clinicopathological parameters and prognosis. We found that UQCRC2 was significantly upregulated in CRC tissues compared with adjacent normal tissues, and immunohistochemical UQCRC2 status was correlated to the depth of invasion (T), lymph node metastasis (N), advanced TNM stage. Multivariate analysis indicated that UQCRC2 remained an independent prognostic factor for poorer overall survival. Furthermore, we determined the role of UQCRC2-knockdown in CRC cells (RKO and HCT116) using lentivirus-mediated small hairpin RNAs (shRNAs). The effects of UQCRC2 knockdown on CRC cells (RKO and HCT116) proliferation were analyzed by cell proliferation and colony formation assay, and cell cycle and apoptosis were assessed by flow cytometry. We found that silencing UQCRC2 suppressed cell proliferation and colony formation in RKO and HCT116 cells, led to a cell cycle arrest and induced cell apoptosis in vitro. These results provided novel insights into the potential role of UQCRC2 in the tumorigenesis and progression of CRC, and revealed that UQCRC2 may serve as a new prognostic and therapeutic target in CRC.     

30岁以下女性乳腺癌临床病理特点及预后分析

目的:探讨青年乳腺癌的临床和病理特点,并对影响其预后的相关因素进行分析.方法:回顾性分析我院1989年12月～2000年12月收治的99例30岁及以下组乳腺癌患者的临床病理资料,观察患者长期生存率,分析临床病理特点及影响预后的因素. 结果:本组99例病理类型中以浸润性癌占多数,高达98.99%;3年生存率为88.78%、5年生存率为68.37%,并随临床分期的增高而降低(P＜0.05﹚.肿瘤直径≤3 cm和＞3 cm的患者其5年生存率分别为75.56%、62.96% (P＜0.05﹚.腋窝淋巴结转移阴性患者与阳性患者5年生存率分别为75.61%、 57.14%(P＜0.05﹚.结论:对于青年乳腺癌患者,肿瘤的临床分期和大小、腋窝淋巴结转移和综合治疗与否是影响预后的独立因素.因此,应尽可能做到早期诊断,早期进行正规的综合治疗,以提高患者的生存率.     

Anti-neutrophil antibodies (anti-MPO-ANCAs) are associated with poor prognosis in breast cancer patients

Anti-neutrophil antibodies are capable of activating neutrophils in sterile environments, releasing extracellular traps containing myeloperoxidase (MPO) and anti-MPO antibodies (MPO-ANCAs or anti-MPO-ANCAs), which have been implicated in the pathogenesis of several diseases. The present study evaluated systemic and tumor tissue levels of anti-MPO-ANCAs breast cancer patients, and its relation to clinicopathological characteristics. Anti-MPO-ANCAs were measured in serum and tissue samples of 150 patients by enzyme-linked immunoassay. Samples were pooled according to clinicopathological characteristics of patients. Higher anti-MPO-ANCAs levels were detected in groups presenting negative clinicopathological characteristics, such as high histological grade tumors and risk factors such as body mass index, menopausal status and early onset at diagnosis. The present data highlights anti-MPO-ANCAs as associated to poor prognosis in breast cancer, a role beyond its actually discussed role in autoimmunity and vasculitis.     

Overexpression of kin of IRRE-Like protein 1 (KIRREL) as a prognostic biomarker for breast cancer

ObjectivesThe purpose of this study was to investigate the expression of Kin of IRRE-Like Protein 1 (KIRREL) and its clinicopathologic significance in breast cancer.Materials and methodsThe mRNA and protein expressions of KIRREL in fresh breast cancer tissue specimens and the corresponding noncancerous tissue specimens were examined by western blot analysis (n = 24) and RT-qPCR (n = 48). KIRREL was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs) in 302 patients. The prognostic roles and clinicopathologic significances in breast cancer were statistically analyzed.ResultsCompared with para-carcinoma tissues, KIRREL mRNA and protein were overexpressed in breast cancer tissues. Immunohistochemical results showed that the high expression rate of KIRREL staining in breast cancer was 43.7% (132/302). Moreover, Expression of KIRREL was significantly correlated with Her2 status and survival outcomes of patients. Patients with both positive expression of KIRREL showed shorter overall survival (OS) and progression free survival (PFS). Additionally, Cox multivariate survival analysis revealed that KIRREL level, age, primary tumor size, tumor stage and distant metastasis were the independent parameter predicting the prognosis of breast cancer patients.ConclusionsKIRREL was overexpressed in breast cancer and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in breast cancer patients.     

USP37 downregulation elevates the Chemical Sensitivity of Human Breast Cancer Cells to Adriamycin

Background: The evolution of adriamycin (ADR) resistance in the treatment of breast cancer often leads to a poor prognosis in patients. Ubiquitin-specific peptidase 37 (USP37) has been recently identified as a modulator in regulating the stemness of breast cancer cells, but its underlying mechanism remains unclear. In this study, we investigated whether USP37 knockdown could hamper the chemical resistance of MCF-7 and MCF-7/ADR cells to adriamycin and elucidated the potential mechanism.Methods: Immunohistochemistry, western blotting, and RT-qPCR assays were performed to detect the USP37 expression in MCF-7 and MCF-7/ADR cells. The efficiency of USP37 knockdown in breast cancer cells was confirmed by western blotting and RT-qPCR assays. We also performed CCK-8 assay, flow cytometry, western blotting, and TUNEL assays to evaluate cell viability and apoptosis in breast cancer cells. In vivo study was performed to detect the tumorigenicity of MCF-7/ADR cells transfected with shScramble or shUSP37#1 under adriamycin treatment.Results: Bioinformatic analysis indicated that USP37 overexpression was positively correlated with adriamycin resistance. The expression levels of USP37 in both MCF-7 and MCF-7/ADR cells increased significantly with the exposure to adriamycin in a dose-dependent manner. It was verified by the observation that USP37 downregulation elevated the inhibitory effects of adriamycin on breast cancer cells, suppressed cell proliferation caused by cell cycle arrest in G1/S transition, as well as induced apoptosis. Furthermore, in vivo study showed that knockdown of USP37 expression also decreased tumorigenicity of MCF-7/ADR cells in mice. TUNEL assay and observation of cell morphology magnified USP37 knockdown synergized with Adriamycin could elevate the apoptosis of MCF-7 and MCF-7/ADR cells. Western blotting assay illustrated that the combination of USP37 knockdown with adriamycin treatment significantly upregulated the expression levels of cleaved caspase 3 and Bax, whereas the expression level of Bcl-2 was inhibited.Conclusion: Knockdown of USP37 gene expression can reverse the resistance of breast cancer cells to adriamycin, and down-regulating USP37 might be a valuable strategy against ADR resistance in breast cancer therapy.     

Up-regulated expression of SNHG6 predicts poor prognosis in colorectal cancer

Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumor formation and development. Small nucleolar RNA host gene 6 (SNHG6) is a recently identified cancer-related lncRNA, and its role in colorectal cancer (CRC) remains to be explored. The aim of this study was to evaluate the expression and function of SNHG6 in CRC. The expression of SNHG6 was detected by real time quantitative RT-PCR (qRT-PCR) in 74 CRC tissues and matched noncancerous tissues (NCTs). Relationships between the expression levels of SNHG6 and various clinicopathological features were analyzed by Chi-square test. The Kaplan-Meier method and log-rank test were applied to compare the survival distribution between different groups. CCK8 assay and colony formation assay were used to measure the effect of SNGH6 on cell proliferation. Flow cytometric analysis was performed to measure the effect of SNHG6 on cell cycle and apoptosis. Our results showed that SNHG6 was up-regulated more than 1.5-fold in 50.0% (37/74) of CRC tissues compared with paired NCTs (P?<?0.0001). High level of SNHG6 expression was strongly associated with advanced tumor stage (P?=?0.026) and predicted poor prognosis of CRC (P?=?0.0215). The Cox proportional hazards model demonstrated that SNHG6 expression was an independent prognostic factor for CRC (HR, 2.568; 95% CI, 1.055–6.252; P?=?0.038). Furthermore, SNHG6 knockdown by siRNA could inhibit cell proliferation, cell cycle progression, and induce apoptosis. Taken together, SNHG6 functions as an oncogene in CRC and appears as a novel prognositic factor for CRC patients.     

RGD Binding to Integrin Alphavbeta3 Affects Cell Motility and Adhesion in Primary Human Breast Cancer Cultures

Integrins mediate cell adhesion to the extracellular matrix. Integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site and has been associated with high malignant potential in breast cancer cells, signaling the onset of widespread metastasis. In recent years, several antagonists of integrin alphavbeta3, including RGD peptides, have been used as potential anti-cancer agents. In the present work, the effect of the linear RGD hexapeptide GRGDSP was studied, for the first time, on breast tumor explants, as well as on well-spread human breast cancer cells from primary cultures, using the explant technique, to clarify the role of this peptide in the suppression of breast cancer cell migration. The results showed that incubation of breast tumor explants with RGD peptide at the beginning of culture development inhibited completely the migration of cancer cells out of the tissue fragment as revealed by electron microscopy. RGD incubation of well-spread breast cancer cells from primary culture resulted in rounding and shrinkage of the cells accompanied by altered distribution of integrin alphavbeta3 and concomitant F-actin cytoskeletal disorganization, as revealed by immunofluorescence. Electron immunocytochemistry showed aggregation of integrin alphavbeta3 at the cell periphery and its detection in noncoated vesicles. However, Western immunoblotting showed no change in beta3 subunit expression, despite the altered distribution of the integrin alphavbeta3. In light of the above, it appears that the RGD peptide plays an important role in the modulation of cell motility and in the perturbation of cell attachment affecting the malignant potential of breast cancer cells in primary cultures.     

Prognostic value of nuclear hepatoma-derived growth factor (HDGF) localization in patients with breast cancer

Hepatoma-derived growth factor (HDGF) plays an important role in tumor progression. Highly expressed HDGF has been found to indicate poor prognosis in many cancers. However, no information is available regarding the prognostic value of nuclear or cytoplasmic HDGF staining level in breast cancer. In the present study, the nuclear or cytoplasmic HDGF staining level was investigated in 86 patients with primary breast cancer by immunohistochemistry; the relationship between nuclear or cytoplasmic HDGF staining level and clinicopathological parameters was examined by Two-tailed Mann-Whitney U-test or Krustal-Wallis. The prognostic value of nuclear or cytoplasmic HDGF staining level in disease-free survival and overall survival was analyzed by Kaplan-Meier methods and log-rank test. We found that the percentage of cases with strong nuclear HDGF staining level was significantly higher in the cases with high tumor grade, high stage, high proliferation index (Ki-67 index>20%), as well as in those with lymph node invasion and recurrence (p<0.05) compared to those without. No significant correlation was found between cytoplasmic HDGF expression and any clinicopathological variables. In addition, disease-free survival and overall survival were significantly lower in patients with high nuclear HDGF expression (level 2) than in those with low nuclear HDGF expression (level 0 and level 1). Further Cox multivariate analysis showed that high nuclear HDGF expression is an independent factor for indicating poor prognosis in breast cancer patients. No significant difference in disease-free survival rate and overall survival was found between different cytoplasmic HDGF staining levels. All these findings suggest that increased nuclear HDGF expression is involved in tumor progression and might be used as a new prognosticator for breast cancer.     

Overexpression of metabolic markers HK1 and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer

Hexokinase 1 (HK1) and pyruvate kinase M2 (PKM2) are two key regulators in glycosis and oncogenic markers in cancers. In the present study, we investigated the expression profile by Western blotting and immunohistochemistry and determined their prognostic values in the gastric cancer. Expression of HK1 and PKM2 was remarkably increased in gastric cancer tissues and was significantly associated lymphatic metastasis and advanced TNM staging. In the COX regression model, HK1 and TNM stage were analyzed as adverse prognostic indicators in gastric cancer. Furthermore, patients with HK1 expression showed remarkable shorter survival duration in both lymphatic metastasis cohort and advanced staging cohort. Our results suggest that overexpression of PKM2 and HK1, especially the latter, significantly associates with lymphatic metastasis, advanced clinical staging and unfavorable prognosis in gastric cancer.     

乳腺癌肿瘤出芽与肿瘤浸润淋巴细胞及患者预后的关系研究

目的:研究肿瘤出芽与乳腺癌临床病理特征、肿瘤浸润淋巴细胞(TILs)以及患者预后的关系。方法:收集2012年1月～2016年12月于暨南大学附属第一医院行手术治疗的178例乳腺癌患者资料及肿瘤组织切片,显微镜下观察乳腺癌组织病理切片中肿瘤出芽和肿瘤浸润淋巴细胞水平,X~2检验分析肿瘤出芽水平与乳腺癌患者临床病理特征和TILs的关系,Log-rank检验分析肿瘤出芽水平与乳腺癌患者无病生存期和总生存期的关系。结果:高肿瘤出芽组患者淋巴结阳性数目多、组织性分级高、脉管癌栓更多;肿瘤出芽数较多的患者TILs的水平较低,而肿瘤出芽数较少的患者TILs水平较高;高肿瘤出芽患者比低肿瘤出芽患者预后较差。结论:乳腺癌肿瘤出芽水平与恶性程度高的临床病理指标密切相关,肿瘤出芽水平与TILs水平呈负相关,是影响乳腺癌预后的重要因素。     

DNA甲基转移酶1在乳腺癌患者中的表达及意义

目的:分析乳腺癌患者外周血中DNA甲基转移酶1(DNA Methyltransferase 1,DNMT1)的表达及其临床意义。方法:本院2018-04-01—2018-11-30期间收治的60例乳腺癌患者(实验组)及同期50例体检健康女性(对照组),采用实时定量PCR(RT-PCR)检测外周血中DNMT1 mRNA的表达情况,Western blot检测两组间DNMT1蛋白表达,比较两组间各指标的差异并分析其与患者临床特征的关系。结果:实验组DNMT1 mRNA在外周血中的表达较对照组显著升高(10.31±3.39 vs 4.74±3.10,P<0.01),DNMT1蛋白表达较对照组亦显著升高(38.48±3.80 vs 23.78±2.95,P<0.01);不同临床特征乳腺癌患者外周血中DNMT1 mRNA和蛋白表达差异无统计学意义(P>0.05)。结论:DNMT1在乳腺癌患者外周血中高表达,与乳腺癌发生密切相关,但与其发展转移无关。     

Modulation of Cathepsin D Routing by IGF-II Involves IGF-II Binding to IGF-II/M6P Receptor in MCF-7 Breast Cancer Cells

The IGF-II/M6P receptor targets cathepsin D to the lysosomes and it also binds IGF-II. Although the binding sites for IGF-II and cathepsin D are distinct, reciprocal interactions between the ligands have been observed. We have demonstrated that proIGF-II expression modulates routing of cathepsin D. To test the hypothesis that IGF-II modulation of cathepsin D routing in MCF-7 cells involves IGF-II binding to the IGF-II/M6P receptor, we expressed a mutant form of IGF-II (Arg⁵⁴ Arg⁵⁵) that does not bind the IGF-II/M6P receptor and evaluated its effects on cathepsin D secretion. Northern blotting, Western and radioimmunoassay analyses confirmed that these cells express high levels of (Arg⁵⁴ Arg⁵⁵) IGF-II mRNA and secretes high levels of IGF-II without modulating the secretion of cathepsin D. These data provide direct evidence that the IGF-II modulation of cathepsin D routing is IGF-II/M6P receptor mediated.     

埃兹蛋白在乳腺癌中的表达及其临床意义

目的 通过检测埃兹蛋白在浸润性乳腺癌、乳腺导管内癌及正常乳腺组织中的表达,探究埃兹蛋白在乳腺癌组织中的表达的临床意义。方法 随机选取南昌大学第一附属医院40例浸润性乳腺癌患者及32例乳腺导管内癌患者,另外选择同期来我院健康体检者22例。通过免疫组化链霉亲和素-过氧化物酶法（S-P）法分别检测埃兹蛋白在22例正常乳腺组织、32例乳腺导管内癌组织和40例浸润性乳腺癌组织中的表达,参照病理结果进行分析。结果 埃兹蛋白在40例浸润性乳腺癌的阳性表达率为72.50%、在32例乳腺导管内癌的阳性表达率为40.63%、在正常乳腺组织中的阳性表达率13.64%,浸润性乳腺癌中埃兹蛋白的表达高于其他两种组织,差异具有统计学意义（P＜0.05）;埃兹蛋白在G3期乳腺癌组织中的表达高于在G1~G2期乳腺癌组织中的表达,差异具有统计学意义（P＜0.05）;埃兹蛋白在淋巴结转移患者中的阳性表达率高于在无淋巴结转移的患者中的阳性表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在＜40岁的患者中的阳性表达率低于在年龄≥40岁的患者中的表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在PR阳性患者中的阳性表达率低于在PR阴性患者中的表达率,差异具有统计学意义（P＜0.05）;乳腺癌患者中埃兹蛋白的表达与组织学分级、腋窝淋巴结转移及年龄呈正相关（P＜0.05）,与PR呈负相关（P＜0.05）;埃兹蛋白在浸润性润腺癌中的表达与乳腺癌临床分期、脉管侵犯、肿瘤大小、患者月经状态以及Her-2、ER、Ki-67的表达无相关性（P＞0.05）。结论 埃兹蛋白在乳腺癌和正常乳腺组织中的表达不同,对判断乳腺肿瘤性质具有重要参考意义;此外,埃兹蛋白能够帮助判断乳腺癌的转移潜能和预后,可能启发乳腺癌新的靶向治疗。     

Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study

PurposeWomen with a remaining lifetime risk of breast cancer of ≥25%, estimated using the International Breast Cancer Intervention Study (IBIS) model, were eligible for the High Risk Ontario Breast Screening Program. This study examined the performance of IBIS 10-year risk estimates in the program.MethodsThis retrospective study included 7487 women aged 30 to 69 years referred to the High Risk Ontario Breast Screening Program between July 1, 2011, and December 31, 2016, with follow-up until December 31, 2018. Model calibration and discrimination were assessed. Analyses were conducted overall and stratified by age (< or ≥50 years). Different 10-year risk thresholds were compared with the current eligibility criteria.ResultsOverall, IBIS overestimated the risk of breast cancer with an expected vs observed case ratio of 1.17 (95% CI = 1.04-1.35). Overestimation was highest in women aged 50 to 69 years (expected vs observed case ratio = 1.29, 95% CI = 1.03-1.69) and for those in the top quartile of risk. Overall discrimination was fair with a concordance statistic of 0.66 (95% CI = 0.63-0.70). Furthermore, when using different 10-year risk eligibility thresholds, most cases would have been missed in the 30 to 49 age group using the 8% 10-year risk threshold, whereas relatively few women aged 50 to 69 would have been ineligible at any of the thresholds examined.ConclusionWe found that IBIS overestimated the risk of breast cancer in this screening cohort but had adequate discrimination. Age-specific risk thresholds should be considered to optimize the program eligibility criteria.     

血清肿瘤标志物和乳腺钼靶在乳腺癌诊断中的应用价值

目的 探讨乳腺钼靶和血清肿瘤标志物在乳腺癌诊断中的应用价值.方法 回顾性分析2013年1月至2014年10月在我院明确诊断的104例乳腺癌患者的临床资料,按照乳腺肿块大小分别统计乳腺钼靶和血清肿瘤标志物CEA、CA153和CA125检测结果,对两种检查方法阳性符合率进行比较,探讨其在乳腺癌诊断中的意义.结果 乳腺肿瘤直径＜2cm组、2～ 5cm组、＞5cm组,钼靶结果阳性率分别为76.7％,87.5％,94.4％;肿瘤标志物联合诊断阳性率分别为33.3％,62.2％,100％.结论 在乳腺癌诊断中,钼靶诊断是乳腺癌诊断的重要方法,其诊断阳性率明显高于血清肿瘤标志物诊断;血清肿瘤标志物在晚期肿瘤中阳性率明显高于早期肿瘤,其在癌症复发监测、肿瘤疗效评价中的有较高价值.     

Both high expression of pyruvate kinase M2 and vascular endothelial growth factor-C predicts poorer prognosis in human breast cancer

Pyruvate kinase M2 (PKM2) and vascular endothelial growth factor-C (VEGF-C) have been known to play an important role in tumorigenesis and tumor progression in breast cancer. However, the association between PKM2 and VEGF-C in breast cancer remains unclear. In the present study, a total of 218 specimens from breast cancer patients and 26 paired breast tumors with adjacent normal tissues as well as two breast cancer cell lines were enrolled to investigate the correlation between PKM2 and VEGF-C. We found that PKM2 and VEGF-C mRNA levels were both significantly increasing in breast tumors compared with adjacent normal tissues. Knockdown of PKM2 mRNA expression resulted in VEGF-C mRNA and protein down-regulated as well as cell proliferation inhibited. A positive correlation between PKM2 and VEGF-C expression was identified by immunohistochemical analyses of 218 specimens of patients with breast cancer (P=0.023). PKM2 high expression was significantly correlated with histological grade (P=0.030), lymph node stage (P=0.001), besides VEGF-C high expression was significantly associated with lymphovascular invasion (P=0.012). While combined high expression of PKM2 and VEGF-C was found to be associated with worse histological grade, more lymph node metastasis, more lymphovascular invasion, shorter progression free survival (PFS), and poorer overall survival (OS) in human breast cancer. The results of the present study suggested that PKM2 expression was correlated with VEGF-C expression, and combination of PKM2 and VEGF-C levels had the better prognostic significance in predicting the poor outcome of patients with breast cancer.     

Syk与VEGF-C在乳腺癌中的表达及临床意义

目的:检测Syk与VEGF-C在乳腺癌组织中的表达情况,探讨它们与乳腺癌病理、临床特征间的关系.方法:应用免疫组化Elvsion法检测64例乳腺癌患者手术切除的癌组织和癌周正常组织中Syk和VEGF-C的表达情况.结果:Syk在正常组织中表达的阳性率为90%,在乳腺癌组织中阳性表达率为59.37%;VEGF-C在正常组织中阳性表达率为0.0%,在乳腺癌组织中的阳性表达率为76.56%;二者比较差异均有统计学意义(P＜0.05).Syk与VEGF-C表达水平均与乳腺癌病理分级、临床分期、淋巴结转移有关(P＜0.05).结论:联合检测乳腺癌中Syk和VEGF-C表达水平,对乳腺癌的早期发现及预后判断有一定参考价值.     

肿瘤转移抑制基因nm23—H1 mRNA在乳腺癌中的转录表达

目的：探讨nm23—H1基因mRNA在乳腺患组织中的表达及其与临床的关系．方法:采用半定量RT—PCR方法，检测30例乳腺患组织nm23—H1的表达．结果:①淋巴结阳性的原发灶组织nm23—H1 mRNAA表达明显低于淋巴结阴性的原发灶组织，Ⅲ期乳腺患组织nm23—H1 mRNA水平较Ⅰ、Ⅱ期的明显低．②多因素分析发现淋巴结转移与nm23—H1 mRNA的表达有显著性相关．结论nm23—H1基因mRNA表达强度与淋巴结转移呈负相关．在乳胰患转移过程中，nm23—H1 mRNA起重要的作用。     

Bcl-2 and Fas Expressions Correlate with Proliferative Specificity of Adipose-derived Stem Cells (ASCs) in Breast Cancer

The tumor microenvironment consists of a dynamic interaction with several cell types including infiltrating cells from the immune system, fibroblasts, adipose derived stem cells (ASCs), and an appropriate milieu for tumor cell growth, expansion and spreading. The aim of this study was to focus on ASCs function by isolating and characterizing them from both breast cancer and normal breast adipose tissues. Therefore, the expressions of Bcl-2 and Fas mRNAs in these cells were determined using real-time quantitative PCR (Q-PCR). Also the proliferative properties of ASCs were compared among different pathological states and normal ASCs utilizing the MTT assay. It was observed that, Bcl-2 mRNA had 5-fold more expression in ASCs of patients than in controls. In contrast, Fas had a lower expression of mRNA in ASCs of patients compared to the controls. ASCs isolated from patients with stage 3 breast cancer had a statistically significant higher rate of proliferation compared to stage 2 and normal ASCs (P-value < 0.001). Based on these results, ASCs of the tumor microenvironment may contribute to tumor growth and progression and consequently protect tumor cells from the host immune response. Therefore these cells may be considered as therapeutic targets of cancer immunotherapy.