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1.
Jang KS  Han HX  Paik SS  Brown PH  Kong G 《Cancer letters》2006,244(2):203-210
The aim of this study is to investigate the possible role of inhibitor of DNA binding (Id-1) overexpression in human breast cancer. We examined Id-1 expression by immunohistochemistry in 263 human breast cancers, 15 in situ lesions and 248 invasive cancers to investigate the relationship between its expression and various clinicopathological factors. Id-1 expression was significantly higher in invasive ductal carcinoma than in in situ ductal carcinoma or other invasive cancer subtypes (P=0.029 and 0.006, respectively). We also examined the association between Id-1 expression and tumor angiogenesis by measuring microvessel densities (MVD). Regarding the endothelial cells of microvessels showed negative or very weak Id-1 expression, Id-1 overexpression was found to be significantly related to MVD (P=0.014). Furthermore, Id-1 overexpression was found to be significantly associated with higher MVD in the ER-negative and node-involved subgroups of breast cancer (P=0.040 and 0.046, respectively). These data indicate that Id-1 overexpression is significantly associated with tumor angiogenesis, especially in the ER-negative and node-positive subtypes of invasive breast cancer. Thus, Id-1 presents a possible therapeutic antitumor target molecule in ER-negative and node-positive breast cancer.  相似文献   

2.
The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.  相似文献   

3.
The phenomenon of tumor angiogenesis is an important aspect of understanding tumor biology. Studies in breast carcinoma have shown microvessel density (MVD) assessed by immunohistochemistry to be of prognostic importance in primary breast cancer. On the other hand, recently developed highly sensitive color-coded Doppler techniques offer a noninvasive method to examine neovascularisation in breast tumors. The purpose of this study was to determine the relationship between Doppler flow parameters and microvessel count assessed by immunohistochemistry. Fifty-three patients with primary breast cancer were examined preoperatively with color-coded Doppler ultrasound. The obtained Doppler frequency spectra were analyzed for peak systolic flow velocity (Vmax). Following surgery, paraffin-embedded microsections were immunohistochemically stained for factor VIII-related antigen. Tumor angiogenesis was assessed by microvessel count under light microscopy. Undifferentiated tumors correlated with high MVD (p=0.009) whereas other clinicopathological parameters were not associated with MVD. Color Doppler signals were detected in 50 out of 53 breast tumors. Evaluation of tumor flow velocity with various clinicopathological parameters showed a significant correlation with tumor size (p=0.0001) and lymph node metastasis (p=0.02). However, there was no significant correlation between MVD and intratumoral blood flow velocity assessed by color-coded Doppler. Our findings showed that Doppler flow measurement did not correlate with the extent of tumor angiogenesis of breast cancer. The present data give circumstantial evidence that microvessel count assessed by immunohistochemistry reflects the microvascular network, whereas tumor vasculature documented by Doppler ultrasound supplies information on the macrovasculature.  相似文献   

4.
Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.  相似文献   

5.
The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Therefore, additional and more precise information is desirable. Although angiogenesis has been suggested as being of prognostic importance in many human cancers, and MUC1, also known as episialin, was thought to be responsible for the development of metastasis, the role of these parameters in prostate cancer remains unclear. The aim of this study was to investigate whether angiogenesis, assessed as microvessel density (MVD), was correlated with the expression of prostate tumor MUC1 and prostate-specific antigen (PSA) or with histopathological grade at diagnosis, and to determine whether any of these factors might provide additional information with regard to prostate tumor biology. Paraffin-embedded material from 60 patients with prostate carcinoma was examined immunohistochemically, using the monoclonal antibody CD31 to determine MVD, and the monoclonal antibodies CCE831 and ER-PR8 to assess MUC1 and PSA expression, respectively. The tumors were categorized according to the Gleason grading system. MUC1 overexpression was significantly related to a high intratumoral angiogenesis (P = 0.02). By contrast, a high PSA expression by prostate cancer cells was associated with low MVD (P = 0.03). No correlation was found between MUC1 and PSA expression. Usually, high-grade tumors were not PSA-expressive and tended to display increased angiogenesis. These differences, however, were not of statistical significance. Similarly, there was no statistically significant association between histological grade and MUC1 expression or angiogenesis. It is suggested that PSA may have a direct suppressive effect on new blood vessel formation in prostate cancer, whereas the expression of MUC1 in this tumor may be connected with an angiogenic phenotype. Additional studies are obviously needed to clarify the precise role of these proteins in prostate cancer.  相似文献   

6.
Liu ZZ  Zhang HW  Wei B  Cui SD 《癌症》2004,23(11):1342-1345
背景与目的:乙酰肝素酶是一类裂解硫酸乙酰肝素的糖苷内切酶,通过降解肿瘤细胞胞外基质及基底膜和促进新生血管形成加速肿瘤扩散和转移。本研究探讨乳腺癌组织中乙酰肝素酶表达与血管生成及预后的关系。方法:采用免疫组化方法,分别应用乙酰肝素酶抗体及CD34单克隆抗体检测120例浸润性乳腺癌组织中乙酰肝素酶的表达和微血管密度(microvesseldensity,MVD),并与患者年龄、肿瘤大小、组织学分级、腋淋巴结转移、临床分期及5年生存率进行相关分析。统计学分析采用χ2检验和t检验、Kaplan-Meier及log-rank检验。结果:①乳腺癌组织中乙酰肝素酶的阳性率为65%,与正常乳腺组织中的阳性率有显著性差异(P<0.05);乳腺癌组织中MVD值为53.84±13.45,显著高于正常对照组(33.32±8.55)(P<0.01)。②乙酰肝素酶的表达与乳腺癌肿瘤大小、组织学分级及腋淋巴结转移率、临床分期、5年生存率密切相关(P<0.05)。③乙酰肝素酶的表达与乳腺癌血管生成有关,乙酰肝素酶高表达组MVD值大于低表达组(P<0.05),两者呈显著正相关(r=0.358,P<0.05)。结论:乙酰肝素酶与乳腺癌血管形成及预后关系密切。  相似文献   

7.
目的 检测畸胎癌生长因子-1(CR-1)蛋白和CD34蛋白在基底细胞样乳腺癌(BLBC)中的表达情况,探讨CR-1在BLBC血管生成和侵袭转移中的作用.方法 采用免疫组织化学法检测60例BLBC、40例非BLBC和20例正常乳腺组织中CR-1蛋白和CD34蛋白的表达,并分析其与BLBC患者CD34标记的微血管密度(MVD)值、年龄、病理组织学分期、淋巴结转移等的关系.结果 CR-1蛋白在BLBC中表达率为70.00%(42/60),明显高于非BLBC的47.50%(19/40)和正常乳腺组织的20.00%(4/20)(均P<0.05),其表达与BLBC患者的临床分期、淋巴结转移、MVD值及肿瘤大小呈正相关(均P<0.05);而与患者年龄无明显相关性(P>0.05).结论 CR-1的表达上调可能与BLBC的血管生成及发生、发展过程有关.CR-1蛋白促进血管生成的作用可能是其促进肿瘤的局部侵袭和远处转移的因素.  相似文献   

8.
目的探讨p33ING1基因、MVD在乳腺癌中表达的意义及其相互关系。方法应用Envision免疫组化法对115例乳腺癌标本进行p33ING1基因和MVD表达检测。结果p33ING1在乳腺癌的阳性表达率为61.7%,与肿瘤浸润分化程度、淋巴结转移及激素受体呈明显负相关。MVD与肿瘤组织学分级及腋下淋巴结转移呈明显正相关,与肿瘤的大小、年龄及激素受体状况无相关性。结论p33ING1阴性者MVD表达明显高于p33ING1阳性者,呈负相关,p33ING1的过度表达及MVD的减少共同参与了抑制细胞生长、促进细胞凋亡的过程。  相似文献   

9.
目的:研究腋淋巴结阴性(ph node negative,LN N)乳腺癌中PTEN蛋白的表达,探讨与微血管密度lym(VD)及患者预后的关系。方法:应用免疫组化S-P法检测81例LN N乳腺癌及20例癌旁乳腺组织中PTEN和MCD34蛋白的表达,分析与各临床病理因素和预后的关系。结果:32.6%的患者PTEN蛋白表达减低或完全阴性表达,PTEN与乳腺癌病理分级,ER状态和复发转移显著相关;PTEN阳性表达组的5年生存率(83.7%)明显高于阴性表达组(66.7%)(P<0.05);PTEN的表达与M VD呈显著的负相关关系(r=-0.552,P<0.01)。结论:PTEN缺失是乳腺癌发生过程中的多发事件,并有抑制血管生成的作用,PTEN缺失和高M V D的LNN乳腺癌患者5年生存率低,两者的检测有助于提高评估LN N乳腺癌患者术后生存的准确性。  相似文献   

10.
It has been suggested that Id-1 has a critical role in the tumour progression and aggressiveness of several human cancers. However, the clinicopathological and biological significance of Id-1 overexpression remains unclear in human primary cancer. To investigate the association between Id-1 expression and cell proliferation or tumour angiogenesis, we examined the cell cycle kinetic indices (the proliferation and apoptotic indices, PI and AI) and intratumoral microvessel density (MVD) in 65 human pancreatic cancers. We also investigated the relationship between its expression and various clinicopathological factors to determine the clinical significance of Id-1 overexpression. Out of a total 65 cases, 32 (49.3%) showed overexpression of Id-1 vs normal tissues. Id-1 expression was found to be significantly associated with MVD (P=0.002). In further analysis of subgroups with higher and lower Id-1 expression, tumours with higher Id-1 expression (scores 4 and 5) showed significantly higher MVD than tumours with lower expression of Id-1 (scores 2 and 3) (111.18+/-57.14 vs 64.13+/-28.19, P<0.001). However, no significant association was found between Id-1 overexpression and patient survival rate. No significant association was also found between Id-1 expression and cell cycle kinetic indices (PI or AI) in pancreatic cancer. Moreover, the overexpression of Id-1 protein was not correlated with any significant clinicopathologic factors. These findings indicate that Id-1 overexpression is closely related with tumour angiogenesis and a higher density of intratumoral vessel, but that it is not associated with a poorer prognosis of survival or a higher cell proliferative potential in human pancreatic cancer.  相似文献   

11.
目的:检测转录因子 Sp1和 VEGF 在乳腺癌中的表达,探讨两者表达的相关性及临床意义。方法:采用免疫组织化学方法检测68例乳腺癌患者肿瘤组织及18例癌旁组织中 Sp1和 VEGF 的表达。结果:Sp1和 VEGF 在68例乳腺癌中表达的阳性率分别为72.05%(49/68)和64.71%(44/68),与在18例正常乳腺组织中表达阳性率(分别为33.3%和16.67%)的差异有统计学意义(P 均<0.01)。Sp1的过表达与乳腺癌的TNM分期、脉管浸润及淋巴结转移相关(P <0.05),而与患者的年龄、肿瘤大小、组织学分级无明显相关性;在乳腺癌组织中 Sp1和 VEGF 的表达之间呈明显正相关(P <0.01)。结论:Sp1和 VEGF 的表达与乳腺癌的生物学行为密切相关,且 Sp1高表达与乳腺癌的血管生成及患者的预后相关。  相似文献   

12.
目的:探讨肿瘤相关巨噬细胞( Tumor-associated macrophages , TAMs )在三阴性乳腺癌( Triple-negative breast cancer ,TNBC)中的表达及其与临床病理因素和预后的关系。方法应用免疫组化染色法检测108例TNBC组织中 TAMs的表达情况,同时检测癌组织中微血管密度( Microvessel density , MVD ),分析TAMs表达与 TNBC临床病理参数、MVD及预后的关系。结果 TAMs表达与患者年龄无关,与肿瘤大小、淋巴结转移、组织学分级、TNM 分期及MVD密切相关。生存分析显示TAMs与TNBC术后5年无病生存时间(Disease-free survival, DFS)及总生存时间(Overall survival,OS)相关;MVD与5年DFS相关,而与OS未见相关性。 Cox回归分析示TAMs是TNBC预后不良的独立危险因素。结论 TAMs高表达提示TNBC预后不良,TAMs可成为判断预后的免疫指标之一。 TAMs与MVD密切相关,可能通过促进瘤内血管增生,从而促进TNBC的生长、侵袭和转移,进一步影响TNBC患者的预后。  相似文献   

13.
目的:研究非小细胞肺癌中MTA1蛋白表达及临床意义。方法:采用免疫组织化学法检测96例非小细胞肺癌组织MTA1蛋白表达情况,并探讨其与非小细胞肺癌临床病理因素的关系。结果:MTA1蛋白在非小细胞肺癌组织中的表达明显高于癌旁正常肺组织(P〈0.05),其表达与患者年龄、性别、病理组织学分型及肿瘤大小无明显相关性(P〉0.05)。MTA1的表达水平与淋巴结转移及TNM分期相关,在有淋巴结转移的病例中的表达(阳性率为75.6%)显著高于无淋巴结转移的病例(阳性率为54.5%),在Ⅲ和Ⅳ期病例中的表达(阳性率为76.3%)显著高于Ⅰ和Ⅱ期(阳性率为55.2%)(P〈0.05)。结论:MTA1表达水平与患者的TNM分期密切相关,在非小细胞肺癌进展包括淋巴结转移的过程中起到重要作用,可能成为潜在的治疗靶点。  相似文献   

14.
李斌  陈武科  陈鹏  廖和和 《陕西肿瘤医学》2009,17(10):1867-1871
目的:探讨MTA1、MMP-9mRNA表达量与乳腺癌淋巴转移的关系及临床意义,初步探讨MTA1、MMP-9mRNA之间的关系。方法:采用免疫组化法对45例侵润性乳腺导管癌中MTA1表达进行检测,原位杂交法对MMP-9mRNA表达进行检测。结果:乳腺癌中MTAI、MMP-9mRNA(肿瘤细胞)、MMP-9mRNA(间质细胞)阳性表达率为71%、49%、58%。MTA1与淋巴结转移相关,与年龄、肿瘤大小、ER、PR、c—erbB-2无相关性;MTA1蛋白定位变化与乳腺癌淋巴结转移相关(P〈0.05);MMP-9mRNA(肿瘤细胞)与临床病理特征均无相关性;MMP-9mRNA(间质细胞)与淋巴结转移正相关(P〈0.05),与PR呈负相关(P〈0.05);MTA1阴性时肿瘤细胞内MMP-9mRNA表达率为38%,MTA1阳性时MMP-9mRNA表达率为50%,无显著性差异。结论:MTA1高表达促进乳腺癌细胞的淋巴结转移,MTA1蛋白定位变化与乳腺癌淋巴结转移相关;MTA1的过度表达可能是导致肿瘤细胞内MMP-9mRNA表达下降的因素。  相似文献   

15.
BACKGROUND AND OBJECTIVES: Growth and metastasis of malignant tumors depend on the angiogenesis. The aim of this study was to elucidate the prognostic significance of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) expression in advanced colorectal carcinoma. METHODS: Totally, 101 patients with surgically resected advanced colorectal carcinomas were enrolled. The tumor expressions of Ang-1 and Ang-2 were evaluated immunohistochemically, and their relationships with clinicopathological factors and prognosis were investigated. Tumor microvessel density (MVD) was also calculated and correlated with angiopoietin expression. RESULTS: Ang-1 and Ang-2 were detected in 26 (25.7%) and 45 (44.6%), respectively, of 101 cancerous lesions. Overexpression of Ang-1 was correlated with high MVD. Overexpression of Ang-2 was correlated with lymph node metastasis, venous invasion, preoperative carcinoembryonic antigen levels, and high MVD (P < or = 0.05). MVD was not significantly upregulated by Ang-1 expression, but was significantly upregulated by Ang-2 expression (P < or = 0.01). However, only patients with Ang-2 overexpression showed a significantly worse prognosis than those without Ang-2 overexpression. Multivariate analysis with logistic regression for 5-year survival revealed that cancerous stage and Ang-2 overexpression were independent prognostic indicators. CONCLUSIONS: The Ang-1 expression correlated with MVD. However, Ang-2 expression was a useful prognostic marker in the management of patients with advanced colorectal carcinoma.  相似文献   

16.
Wang J  Ou ZL  Hou YF  Luo JM  Shen ZZ  Ding J  Shao ZM 《Oncogene》2006,25(54):7201-7211
In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.  相似文献   

17.
赵征  赵新汉  袁勇 《现代肿瘤医学》2006,14(10):1231-1232
目的:研究乳腺癌中C-erbB-2的过表达与临床病理因素间的相关性。方法:采用免疫组化法检测120例乳腺癌组织中C-erbB-2的表达,采用Pearsonχ2统计学方法分析与临床病理指标的关系。结果:120例乳腺癌组织中C-erbB-2过表达阳性率为36.7%(44/120)。C-erbB-2的表达与肿瘤直径、淋巴结转移数、临床分期均呈正相关。结论:C-erbB-2的过表达与乳腺癌侵袭和转移密切相关,是乳腺癌预后指标。  相似文献   

18.
目的:分析Bcl-3与VASP在乳腺癌中的表达及与临床病理特征的关系。方法:利用BCIP数据库分析Bcl-3与VASP在乳腺癌中的表达情况及相关性;选取85对女性乳腺癌组织及癌旁组织,利用免疫组化技术检测Bcl-3与VASP表达情况,并分析两者表达相关性以及与乳腺癌临床病理学参数的关系。结果:BCIP数据库与免疫组化结果发现,Bcl-3与VASP在乳腺癌中表达异常升高,且呈正相关;Bcl-3表达水平与肿瘤大小(P=0.011)、淋巴结转移(P<0.001)及TNM分期(P<0.001)呈正相关,VASP表达与组织学分级和TNM分期呈正相关(P<0.001);另外,Bcl-3与VASP共阳性的发生与高级别(P=0.036)、有淋巴结转移(P<0.001)的TNM分期偏晚(P=0.003)的乳腺癌密切相关。结论:Bcl-3与VASP均在乳腺癌中异常高表达,且两者之间存在正相关;两者均可作为乳腺癌临床病理学诊断的潜在参考指标。  相似文献   

19.
目的:检测乳腺癌中MTA1、CD44V9mRNA的表达,并结合临床、病理资料,分析其对乳腺癌侵袭和转移的影响及作用。方法:应用原位杂交和免疫组织化学方法,对45例乳腺癌患者的癌组织进行CD44V9mRNA及MTAl表达的检测,对实验结果进行半定量分析,应用等级相关分析对实验数据进行统计学处理。结果:MTA1及CD44V9mRNA在乳腺癌中的表达率分别为71%和76%,在淋巴结转移组两者的阳性表达率明显高于无淋巴结转移组(P〈0.05);两者表达间无明显相关性(P=0.136)。结论:MTA1及CD44V9mRNA高表达与乳腺癌的转移密切相关,可以作为判定乳腺癌转移及预后的重要指标。  相似文献   

20.
目的 探讨磷脂酰肌醇-3-激酶相关激酶(PIKK)家族成员生殖器形成抑制基因1(SMG 1)、哺乳动物雷帕霉素靶蛋白(mTOR)及mTOR调节相关蛋白(Raptor)在乳腺癌组织中的表达及临床意义。方法 收集2014年1月至2015年7月乳腺癌组织68例及配对癌旁组织40例和乳腺纤维腺瘤组织40例,采用免疫组化SP法检测以上组织中SMG 1的表达情况,实时定量PCR(QPCR)检测mTOR和Raptor的表达水平,分析3者表达与乳腺癌临床病理特征的关系,并采用Spearman法分析3者表达的相关性。结果 乳腺癌组织中SMG 1的阳性表达率为27.9%(19/68),低于癌旁组织的77.5%(31/40)和乳腺纤维腺瘤组织的82.5%(33/40),差异有统计学意义(P<0.05);乳腺癌组织中mTOR和Raptor的相对表达量分别为2.754±0.213和4.137±0.626,均高于癌旁组织和乳腺纤维腺瘤组织(P<0.05)。SMG 1表达与乳腺癌的肿瘤大小、淋巴结转移及组织学分级均有关(P<0.05),mTOR表达与乳腺癌的肿瘤大小、TNM分期及组织学分级均有关(P<0.05),Raptor表达与乳腺癌的肿瘤大小、淋巴结转移及组织学分级均有关(P<0.05);SMG 1表达与mTOR和Raptor表达呈负相关(r=-0.547、r=-0.415, P<0.05),mTOR和Raptor表达呈正相关(r=0.664, P<0.05)。结论 乳腺癌组织中mTOR、Raptor呈高表达而SMG 1呈低表达,3者表达均与乳腺癌的肿瘤大小、组织学分级有关,提示PIKK家族成员SMG 1、mTOR和Raptor可能在乳腺癌发生、发展中具有重要意义。  相似文献   

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