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1.
The invasion and metastasis of tumor cells is a major cause of mortality in cancer patients. In the current study, we investigated the expression of fascin, an actin-bundling motility-associated protein, in 210 invasive breast carcinomas with corresponding 5-year clinical follow-up. Fascin expression was compared with hormone receptor (ER/PR) status, HER2 status, cancer grade, cancer stage, metastasis pattern, disease-free survival, and overall survival. Fascin expression was seen in 16% (33/210) of the cases and correlated with ER negativity (22/33, P < 0.001), PR negativity (21/33, P < 0.001), Bloom-Richardson grade 3 (19/29, P < 0.001), and advanced stage (stage 3 or 4, P = 0.04).There was no correlation between fascin expression and HER2 status or pattern of metastases. Patients whose tumors were positive for fascin showed both a decreased mean disease-free survival (74.44 versus 100.52 months, P = 0.002) and mean overall survival (77.58 versus 98.98 months, P = 0.002), independent of tumor stage and HER2 status, but not independent of ER/PR status or cancer grade. Given fascin's role in altering cell motility, overexpression may contribute to a more aggressive clinical course in ER/PR-negative breast cancers. If so, then fascin may represent a new molecular target for therapeutic intervention in patients with ER-negative breast cancer.  相似文献   

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PURPOSE: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. EXPERIMENTAL DESIGN: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. RESULTS: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disease-free survival independent of age, pT stage, histologic grade, estrogen receptor (ER), progesterone receptor (PR), as well as HER2 status (P = 0.028; hazard ratio, 1.60; 95% confidence interval, 1.05-2.44). Recently, so-called triple-negative (HER-2, ER, and PR) breast cancer has received increased attention. We noticed a similar association of Ep-CAM with disease-free survival in the triple-negative group as for the entire cohort. CONCLUSION: In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer. This suggests that Ep-CAM may be a well-suited target for specific therapies particularly in HER-2-, ER-, and PR-negative tumors.  相似文献   

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Objective: The aim of the study was to investigate the expression and clinical significance of aldehyde dehydrogenase 1 (ALDH1) in breast cancer patients. Methods: The expression of ALDH1 protein was examined by immunohistochemical staining in 96 breast cancer tissues. The disease-free survival analysis of patients was evaluated based on the clinical follow-up data. Results: Expression of ALDH1 protein had significant correlations with ER, PR, and HER2 proteins (P < 0.05), but had no significant correlation...  相似文献   

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Objective: To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods: A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were available for these patients. Results: Luminal A (ER+ and/or PR+, HER2-) had a favorable disease-free survival (DFS) and overall survival (OS) c...  相似文献   

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ABSTRACT: INTRODUCTION: We investigated the status of estrogen receptor alpha (ERalpha), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. METHODS: The study group included 120 breast cancer patients. ERalpha, PR and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. RESULTS: Using the Allred score of >3 as a threshold, conversion of ERalpha and PR in brain metastases occurred in 29% cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERalpha (P=0.021) and PR (P=0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. CONCLUSIONS: Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly impact survival.  相似文献   

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It has been suggested that type 2 diabetes mellitus may affect breast cancer prognosis, possibly due to increased diabetes-related comorbidity, or direct effects of insulin resistance and/or hyperinsulinemia. The aim of this study was to determine the impact of diabetes on disease-free survival (DFS) following mastectomy for breast cancer patients. The cases included in this retrospective study were selected from breast cancer women who had undergone mastectomy and completed adjuvant chemotherapy from 1998 to 2010. Patients were classified into two groups: diabetic and non-diabetic. Patients' age, sex, menopausal status, body mass index (BMI), histopathological features, tumor size, lymph node involvement, hormone receptor and HER2-neu status, and treatment types were recorded. There were 483 breast cancer patients included in the study. Postmenopausal patients' rate (53.7% vs. 36.8%, P = 0.016) and mean BMI levels were statistically higher (32.2 vs. 27.9, P = 0.007) in diabetic patients. There was no statistical difference for histological subgroup, grade, ER and PR positivity, HER2-neu overexpression rate, and tumor size between the diabetic and non-diabetic group. Lymph node involvements were statistically higher in diabetic patients compared with non-diabetic patients (P = 0.013). Median disease-free survival is 81 months (95% CI, 61.6-100.4) in non-diabetic patients and 36 months (95% CI, 13.6-58.4) in diabetic patients (P < 0.001). The odds ratio of recurrence was significantly increased in those with HER2-neu overexpression and lymph node involvement and decreased with PR-positive tumors. Our results suggest that diabetes is an independent prognostic factor for breast cancer.  相似文献   

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《Annals of oncology》2009,20(12):1953-1958
BackgroundWe evaluated discordance in expression measurements for estrogen receptor (ER), progesterone receptor (PR), and HER2 between primary and recurrent tumors in patients with recurrent breast cancer and its effect on prognosis.MethodsA total of 789 patients with recurrent breast cancer were studied. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%, respectively. Primary and recurrent tumors were classified as triple receptor-negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e. expressing at least one receptor). Discordance was correlated with clinical/pathological parameters.ResultsDiscordance for ER, PR, and HER2 was 18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had significantly better post-recurrence survival (PRS) than discordant cases; patients with discordant receptor status had similarly unfavorable survival as patients with concordant TNBC. IHC scores for ER and PR showed weak concordance between primary and recurrent tumors. Concordance of HER2–FISH scores was higher.ConclusionsConcordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.  相似文献   

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目的:检测乳腺癌组织中激素受体(hormonereceptor,HR)、人表皮生长因子受体2(humanepidermalgrowthfactOrreceptor2,HER-2)和特异性核基质结合蛋白(specialATrichsequencebindingprotein1,SATB1)的表达,探讨HR与HER-2、SATB1及临床病理参数的关系。方法:应用免疫组织化学方法检测乳腺癌患者雌激素受体(estrogenre-ceptor,ER)、孕激素受体(progesteronereceptor,PR)、HER-2及SATB1蛋白的表达,荧光原位杂交方法检测HER-2基因扩增状态,统计学方法分析HR(包括ER及PR)的表达与HER-2、SATB1及临床病理参数之间的相关性。结果:乳腺癌组织ER及PR的表达均与患者年龄正相关(r=0.286,P=0.010;r=0.249,P=0.026),ER的表达与肿瘤分级负相关(r=-0.306,P=0.006);ER及PR的表达与肿瘤大小、组织学类型、淋巴转移情况及TNM分期均无明显相关性,P值均〉0.05。HR的表达与SATB1、HER-2及SATB1/HER2双阳性表达均呈负相关关系(r=-0.248,P=0.027;r=-0.392,P〈0.001;r=-0.150,P〈0.001)。结论:HR阳性患者治疗及预后相对较好;乳腺癌组织HR的表达与HER-2和SATB1呈负相关关系,三者之间可能存在相互联系的信号通路。  相似文献   

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BACKGROUND AND OBJECTIVES: We analyzed the clinicopathologic characteristics and tumor biology of metachronous bilateral breast carcinoma with regard to p53, HER2 and hormone receptor status. METHODS: A consecutive series of 54 female metachronous bilateral breast carcinoma patients treated at the National Cancer Center Hospital between 1980 and 1997 were the primary source of these retrospective data. Clinicopathologic background factors were analyzed, and immunohistochemical staining for p53, HER2, and hormone receptor status was carried out on paraffin-embedded specimens. RESULTS: There were no significant differences in clinical stage, p53 and HER2 expression levels between the first and second primary tumors. The positive rates for ER and PR were 48% (25 of 52) and 46% (25 of 54) for the first tumors, but only 19% (10 of 52) and 32% (17 of 54) for the second tumors (P = 0.004 for ER, P = 0.16 for PR), showing a significant loss of ER. CONCLUSIONS: Our findings indicate that p53 and HER2 expression levels in the second tumors might be the same as those of the first tumors in metachronous bilateral breast carcinoma; however, loss of ER was more frequently observed in the second primary tumors than in the first tumors.  相似文献   

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BackgroundThe prognostic value of syndecan-1 (SDC1, also called CD138) in breast cancer remains controversial. Therefore, we performed a meta-analysis to assess the clinical significance of SDC1 expression in breast cancer.Materials and methodsVarious databases were searched to evaluate possible correlations between SDC1 protein or mRNA expression and prognostic significance in breast cancer. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were applied to perform a quantitative meta-analysis.ResultsA total of 1305 breast cancer patients from 9 eligible studies were included in this meta-analysis. Significant associations between elevated SDC1 protein expression and poor disease-free survival (DFS) (HR = 1.55, 95% CI: 1.12–2.14; P = 0.007) and overall survival (OS) (HR = 2.08, 95% CI: 1.61–2.69; P < 0.001) were observed. In addition, enhanced SDC1 protein expression correlated with negative estrogen receptor (ER) expression (OR, 2.38; 95% CI, 1.64–3.44; P < 0.001) and positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.77; 95% CI, 1.14–2.76; P = 0.01). However, increased SDC1 protein expression did not correlate with relapse-free survival (RFS) (HR = 0.33, 95% CI: 0.03–3.13; P = 0.33). There were no additional significant correlations observed between SDC1 protein expression and other clinical factors, including tumor size, lymph node involvement, nuclear grade, and progesterone receptor (PR) expression.ConclusionThe results of this meta-analysis demonstrate that increased SDC1 protein expression in breast cancer is significantly associated with worse prognosis in terms of DFS and OS, and an aggressive phenotype is associated with negative ER expression and positive HER2 expression.  相似文献   

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The role of beta-catenin in breast cancer and its prognostic value is controversial. The prognostic value had been assessed previously in a series of nonquantitative immunohistochemical studies with conflicting results. In efforts to clarify the relationship between beta-catenin protein expression and breast cancer prognosis, we have assessed a retrospective 600 case cohort of breast cancer tumors from the Yale Pathology archives on tissue microarrays. They were assessed using automated quantitative analysis (AQUA) with a series of array-embedded cell lines for which the beta-catenin concentration was standardized by an ELISA assay. The expression levels of the standard clinical markers HER2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67 were also assessed on the same cohort. X-tile software was used to select optimal protein concentration cutpoints and to evaluate the outcome using a training set and a validation set. We found that low-level expression of membranous beta-catenin is associated with significantly worse outcome (38% versus 76%, 10-year survival, validation set log-rank P = 0.0016). Multivariate analysis of this marker, assessed in a proportional hazards model with tumor size, age, node status, nuclear grade, ER, PR, HER2, and Ki-67, is still highly significant with a hazard ratio of 6.8 (P < 0.0001, 95% confidence interval, 3.1-15.1). These results suggest that loss of beta-catenin expression at the membrane, as assessed by objective quantitative analysis methods, may be useful as a prognostic marker or may be part of a useful algorithm for prognosis in breast cancer.  相似文献   

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目的探讨雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体2(HER-2)表达状态在双侧原发性乳腺癌(bilateral primary breast cancer,BPBC)患者第一癌与第二癌间的异同及其与预后的关系。方法回顾1961年1月至2007年12月间本院收治并确诊的565例BPBC患者临床资料,BPBC患者占同期全部乳腺癌患者的2.09%,其中同时性双侧乳腺癌(以6个月为界)198例占35.04%。采用免疫组织化学SP法进行ER、PR、HER-2检测。采用SPSS14.0中X^2检验比较ER、PR、HER-2在同时性和异时性BPBC表达的一致率及BPBC第一癌与第二癌ER、PR、HER-2的阳性率;采用Kaplan—Meier生存分析法研究BPBCER、PR和HER-2与患者预后的关系。结果同时性双侧原发性乳腺癌激素受体表达一致率要高于异时性双侧原发性乳腺癌(ER:X^2=5.30,P=0.02;PR:X^2=15.88,P=0,00)。双侧原发性乳腺癌两侧癌灶ER、PR和HER-2的表达没有区别(ER:X^2=2.02,P=0.16;PR:X^2=0.86,P=0.35:HER-2:X^2=0.70,P=0.79)。BPBC两侧ER和HER-2表达状况与其预后相关(ER:P=0.03,HER-2 P=0.03)。结论BPBC两侧癌灶激素受体及HER-2表达状态相仿。同时性BPBCER、PR表达的一致性高于异时性BPBC。两侧乳腺癌均检测激素受体和HER-2的表达对预后判断有一定的指导意义。  相似文献   

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The purpose of this study was to analyze whether inter-site variation types on estrogen receptor (ER) and HER2 expression may be a predictive factor for evaluating the effectiveness of endocrine therapy in patients with ER-positive and HER2-positive breast cancer. A total of 366 consecutive women with invasive breast cancer who had undergone curative surgical treatment between 1996 and 2001 were included in this study. ER status was evaluated using the Allred score and HER-2 status was evaluated according to the HercepTest. In ER-positive and HER2-positive tumors, the expression of ER and HER2 was described as the co-expressed type or the differently expressed type using double staining with ER and HER2. Of the 366 patients, 249 (68.1%) were positive for ER and 74 (20.2%) were positive for HER2. ER-positive and HER2-negative tumors were found in 221 patients (60.4%), ER-negative and HER2-negative in 71 (19.4%), ER-negative and HER-2-positive in 46 (12.6%), and ER-positive and HER2-positive in 28 (7.7%). HER2 status was inversely correlated (p<0.01) with ER status. In ER-positive tumors, an inverse correlation between ER and HER2 was also observed. The co-expressed type was found in 10 patients, and the differently expressed type was found in 18. There was no difference in tumor size and nodal involvement between the two types. There was no significant difference in disease-free survival between patients with the co-expressed type tumor and the differently expressed type tumor. In patients with the differently expressed type tumor, those who received antiestrogen therapy showed a significantly better disease-free survival rate than those who did not receive antiestrogen therapy. As for patients with the co-expressed type of tumor, no significant difference in disease-free survival was observed between patients with and without antiestrogen treatment. The present study suggests that the co-expressed type of tumour might be a resistant factor to antiestrogen therapy in ER-positive and HER2-positive breast cancer.  相似文献   

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PURPOSE: Death-associated protein (DAP)-kinase is a new Ser/Thr kinase involved in cell apoptosis and tumor suppression, the expression of which has been correlated to invasive potential and metastasis in several human neoplastic tissues. We analyzed the level of DAP-kinase expression in breast cancer specimens and its correlation with survival. EXPERIMENTAL DESIGN: One hundred twenty-eight breast cancer specimens were analyzed by immunohistochemistry. Patient records were studied retrospectively for demographic characteristics, clinical data, hormonal treatment, outcome, and survival. DAP-kinase protein expression was also studied in normal breast cells primary cultures under estrogen and antiestrogen treatment. RESULTS: Among the 128 patients, 30 showed a DAP-kinase staining < or = 20%, whereas 98 had a staining over 20%. Mean follow-up time was 62 months. The association between tumor Scarff-Bloom and Richardson grade (P = 0.009), estrogen receptor and progesterone receptor expression (P = 0.002 and 0.001, respectively), tumor size (P = 0.05), Bcl-2 expression (P = 0.004), and DAP-kinase immunostaining in the ductal carcinoma group was highly significant. Overall (64 months) and disease-free (63 months) survival in the high DAP-kinase expression group were significantly longer compared with the women whose tumors showed a loss of DAP-kinase expression (51 and 43 months, respectively). DAP-kinase protein was strongly expressed in normal breast tissue and in human breast epithelial cells primary cultures. Estradiol decreased DAP-kinase expression in these cells, arguing for hormonal regulation of the protein. CONCLUSIONS: Loss of DAP-kinase expression negatively correlates to survival and positively correlates to the probability of recurrence in a very significant manner. DAP-kinase thus constitutes a novel and independent prognosis marker for breast cancer.  相似文献   

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目的:观察radixin蛋白表达与乳腺癌临床病理参数的相关性及临床意义。方法:收集散发性乳腺癌标本278例,乳腺纤维腺瘤组织46例,应用SP免疫组化法检测radixin蛋白的表达情况,并分析与乳腺癌患者临床病理参数的相关性。结果:乳腺癌中radixin蛋白表达阳性率为73.7%(205/278),乳腺纤维腺瘤中radixin蛋白表达阳性率为32.6%(15/46),与乳腺纤维腺瘤组织比较,radixin蛋白阳性表达率显著高于乳腺纤维腺瘤组织(P<0.000 1)。在乳腺癌组织中,radixin蛋白表达与患者TNM分期、HER-2表达正相关,在临床分期高、HER-2表达阳性的组织中,radixin蛋白表达阳性率明显增加(P=0.023,P=0.007)。radixin蛋白表达与患者年龄、绝经状态、淋巴结转移、肿瘤大小、p53蛋白表达均未见相关性。生存分析发现,radixin蛋白表达与乳腺癌患者总体生存期无关,radixin阳性表达的乳腺癌患者,RFS时间明显缩短(P<0.05)。结论:乳腺癌组织中radixin蛋白高表达与患者临床分期、HER-2表达和临床预后相关。  相似文献   

18.
The clinical behavior of human epidermal growth factor 2 (HER2)-positive breast cancer, including pathologic complete response rate and pattern of relapse and metastasis, differs substantially according to hormone receptor (HR) status. We investigated various histopathologic features of HER2-positive breast cancer and their correlation with HR status. We retrospectively analyzed tumors of 450 HER2-positive breast cancer patients treated with chemotherapy and 1 year of trastuzumab. HR?/HER2+ tumors showed higher nuclear grade, less tubule formation, higher histologic grade, frequent apocrine features, diffuse and abundant lymphocytic infiltration, strong HER2 immunohistochemical staining (3+), higher average HER2 copy number and HER2/CEP17 ratio, the absence of HER2 genetic heterogeneity, and greater p53 expression than HR+/HER2+ tumors. An inverse correlation was observed between estrogen receptor or progesterone receptor Allred score and average HER2 copy number or HER2/CEP17 ratio. The percentage of ductal carcinoma in situ (DCIS) within the tumor was negatively correlated with ER Allred score, but positively correlated with average HER2 copy number and HER2/CEP17 ratio. Pathologic tumor size and DCIS percentage also showed a significant inverse correlation. Ratio of metastatic to total examined lymph node number was significantly correlated with average HER2 copy number and HER2/CEP17 ratio. High pT stage (hazard ratio, 2.370; p = 0.027), the presence of lymphovascular invasion (hazard ratio, 2.806; p = 0.005), and HR negativity (hazard ratio, 2.202; 1.074–4.513; p = 0.031) were found to be independent prognostic indicators of poor disease-free survival. In conclusion, HR+/HER2+ and HR?/HER2+ breast cancer showed distinct histopathologic features that may be relevant to their distinct clinical behavior.  相似文献   

19.
目的:探讨不同的ER、PR表达对原发性侵袭性乳腺癌患者预后的影响,重点研究ER+/PR- 和ER-/PR+ 单阳性表型肿瘤的临床病理特征和预后差异。方法:回顾性分析1998年10月至2004年5 月间天津医科大学附属肿瘤医院收治的1 054 例原发性侵袭性乳腺癌患者的病例资料及随访结果,比较不同的ER、PR表达乳腺癌患者的临床病理特征和预后,明确ER+/PR- 和ER-/PR+ 单阳性表型肿瘤之间存在的差异。计算生存率采用Kaplan-Meier 方法,生存率比较应用Log-rank 检验。经COX多因素分析得出独立的预后影响因素。结果:ER+/PR- 表型肿瘤易出现于年长、绝经后的女性,肿瘤直径较小,组织分化程度较高。生存分析显示:ER+/PR+ 组预后优于ER-/PR- 组(OS:P=0.000,DFS :P=0.000),ER或PR单阳组预后介于ER+/PR+ 组和ER-/PR- 组之间。相对于ER-/PR- 表型肿瘤,ER+/PR- 的生存优势强于ER-/PR+ ,ER+/PR- 的无瘤生存优于ER-/PR+(P=0.035),而两者之间总体生存无明显差异(P=0.890)。 不同的ER、PR阳性表达是影响乳腺癌患者内分泌治疗的无瘤生存的独立因素(P=0.023)。 结论:ER+/PR- 和ER-/PR+ 是两种临床病理特征和预后完全不同的乳腺癌,ER-/PR+ 肿瘤表现的侵袭性行为更强,应该采取更为积极的治疗措施。ER-/PR+ 表型乳腺癌可能具有独特的生物学特征。   相似文献   

20.
Caveolin-1 and -2 (CAV1, CAV2) are closely linked genes localised to the fragile region of 7q31 (FRA7G), and loss of heterozygosity involving this region has been reported in breast cancer. Several studies have suggested that CAV1 is a negative regulator of HER2/neu signal transduction in vitro. However, the clinical significance of CAV1 in breast cancer has not yet been clarified. We examined quantitatively the mRNA levels of CAV1, CAV2 and HER2/neu in 162 cases of breast cancer using real-time PCR. Caveolin-1 and -2 protein expression was also examined by Western blotting and immunohistochemistry. We then evaluated for correlations between CAV1, CAV2 and HER2/neu gene expression and clinicopathologic factors in the 162 breast cancer cases. Results showed higher HER2/neu mRMA levels and lower CAV1 and CAV2 mRMA levels in breast cancer tissues than in corresponding normal tissues (P<0.001). Caveolin-1 and -2 protein expression levels were also suppressed in cancer tissues compared to normal tissues by Western blotting. Immunohistochemistry revealed that CAV1 and CAV2 proteins were abundantly expressed in mammary gland myoepithelial cells, but only weakly in ductalepithelial cells. Reduced CAV1 mRNA level was significantly associated with increasing tumour size (P=0.041), and negative oestrogen receptor status (P=0.021). There was also a significant association between low CAV2 mRNA level and negative progesterone receptor status (P=0.013), and between high HER2/neu mRNA level and negative hormonal receptor status (ER, P=0.029, PgR, P=0.019). While there was no relationship between HER2/neu and CAV1 mRNA levels, a significant association between CAV1 and CAV2 mRNA levels was observed (P<0.001). Our results indicated that CAV1 suppression correlated closely with that of CAV2 in breast cancer, that CAV1 level was inversely correlated with tumour size, and that CAV1 and CAV2 levels were correlated with hormonal receptor status. Therefore, CAV1 and CAV2 play an important role in tumour progression in breast cancer patients.  相似文献   

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