miR-145在乳腺癌中表达及意义

目的 研究一种微小RNA(miR-145)在人乳腺癌及乳腺良性病变组织中的表达,分析miR-145的表达与乳腺癌临床病理特征的关系及其对乳腺癌发生发展的意义.方法 采用组织芯片平台,应用原位杂交方法 检测91例乳腺癌和38例乳腺良性病变组织(包括21例纤维腺瘤,17例乳腺腺病)miR-145表达.结果 乳腺癌miR-145高表达率较乳腺良性病变降低(31.9%和60.5%,P<0.01);乳腺癌miR-145高表达率与肿瘤腋淋巴结转移(P<0.01),TNM高分期(P<0.05),c-erbB-2过表达(P<0.01)状况均相关;乳腺癌miR-145表达与患者年龄、肿瘤大小、组织学分级、ER、PR均无相关性(均P>0.05).结论 miR-145表达异常可能参与了乳腺癌的发生、发展过程,是一个潜在的乳腺癌分子标记物.     

乳腺癌中CD47的表达及其临床意义

目的探讨CD47在乳腺癌中的表达及其临床意义。方法采用免疫组化SP法检测217例乳腺癌组织芯片和40例乳腺良性病变组织中CD47蛋白的表达,分析其表达与乳腺癌临床病理特征、肿瘤复发及生存率的关系。结果乳腺癌组织中CD47蛋白表达水平显著高于乳腺良性病变组织(P0.01),且其表达与乳腺癌TNM分期、组织学分级、ER、PR表达明显相关(P均0.05);与患者年龄、绝经状态、HER-2表达情况无显著相关(P均0.05)。CD47蛋白在复发组中的阳性率明显高于未复发组(P0.05),是乳腺癌复发的特征之一。此外,CD47蛋白阳性的乳腺癌患者5年无瘤生存率低于其阴性的乳腺癌患者,但差异无显著性(P0.05)。结论 CD47在乳腺癌组织中高表达,与患者的TNM分期、组织学分级、ER、PR表达及其肿瘤复发均相关,检测其表达具有一定临床意义。     

乳腺浸润性导管癌中CD44、TRIM24、TAGLN-2、ER、PR的表达及其临床意义

目的探讨PI3K-AKT信号通路分子CD44、TRIM24、TAGLN-2、ER、PR在乳腺浸润性导管癌中的表达及其临床意义。方法应用免疫组化EnVision两步法检测73例乳腺浸润性导管癌组织中CD44、TRIM24、TAGLN-2、ER、PR的表达,分析其与临床病理特征的关系及表达的相关性。结果 CD44、TRIM24、TAGLN-2、ER、PR的表达与患者年龄、肿瘤大小、组织学分级及淋巴结转移无明显相关性。CD44与TAGLN-2表达呈正相关(r=0.311,P=0.007);TRIM24与TAGLN-2表达呈正相关(r=0.421,P=0.000);CD44与ER表达呈负相关(r=-0.285,P=0.015);ER与PR表达呈正相关(r=0.598,P=0.000)。CD44阳性组患者术后5年累积生存率低于CD44阴性组(P=0.002);ER阳性组患者术后5年累积生存率高于ER阴性组(P=0.026)。结论在乳腺癌中CD44、TRIM24可能通过激活PI3K-AKT信号通路上调TAGLN-2表达,CD44可能通过激活PI3KAKT信号通路下调ER表达。CD44、ER有望成为预测乳腺浸润性导管癌患者预后的辅助因子,联合检测CD44、ER、PR的表达有助于乳腺浸润性导管癌治疗策略的选择及优化。     

PTP1B在ER阳性乳腺癌中的表达及临床预后意义

目的探讨PTP1B在ER阳性乳腺癌中的表达及其临床与预后的意义。方法应用免疫组化SP两步法检测179例乳腺癌标本中PTP1B蛋白的表达,分析PTP1B表达与乳腺癌临床病理特征及预后的关系。结果在ER阳性乳腺癌中,PTP1B表达水平与T分期(P=0.038)、淋巴结转移(P=0.021)、肿瘤分期相关(P=0.008)。Kaplan-Meier检测结果显示,与PTP1B低表达组相比,PTP1B高表达组患者的总生存率更低(P=0.006)。多因素分析显示T分期、腋窝淋巴结转移和PTP1B表达是影响患者总生存的独立预后因素。结论 ER阳性乳腺癌中PTP1B的表达与肿瘤进展和患者不良预后密切相关,PTP1B可能是ER阳性乳腺癌预后不良评估的指标之一。     

乳腺肿瘤组织生长抑素受体检测及其临床意义

探讨乳腺良、恶性肿瘤SSR表达的差异对乳腺肿瘤良、恶性的鉴别诊断的价值, 观察SSR表达与ER、PR表达的相关性, 预测乳腺肿瘤生长抑素受体显像的临床价值. 将手术切下的标本分成4组: 乳腺肿瘤恶性组(恶性组)及其对照组(癌旁组), 乳腺肿瘤良性组(良性组)及其对照组(瘤旁组).采用RBA法测定各组织的SSR表达, 采用免疫LsAB法测定ER、PR表达.结果:(1)恶性组、癌旁组、良性组、瘤旁组SSR表达分别为108.6±67.3fmol/mg pr、37.2±9.6fmol/mg pr、43.4±12.6fmol/mg pr、33.9±10.2fmol/mg pr, 恶性组比其对照组及良性组都高, 差异有显著性(P值分别为＜0.001、＜0.01),而良性组与其对照组则无显著性差异(P＞0.05);(2)SSR与ER、PR表达的相关系数分别为0.859、0.750.因此, 大多数乳腺癌组织表达高密度的SSR,可用SSR显像来做良、恶性肿瘤的初步鉴别, SSR表达与ER、PR表达有良好的相关性, 可预测肿瘤恶性程度及其患者预后.     

乳腺癌中雄激素受体的表达及与雌激素、孕激素受体表达的关系

目的 研究乳腺癌组织中雄激素受体(AR)表达的意义及其与雌激素受体(ER)、孕激素受体(PR)表达的关系.方法 应用免疫组化染色检测200例乳腺癌中AR及ER、PR的表达,并结合相关临床病理指标进行比较分析.结果 乳腺癌组织中有113例表达AR,121例表达ER,109例表达PR.在肿瘤＜2cm者中AR阳性率为66.67％(42/63),肿瘤2～5cm者中AR表达率为55.17％ (64/116),肿瘤＞5cm者AR表达率为33.33％(7/21).组织学分级Ⅰ级者肿瘤AR阳性表达率为67.8％(36/53),组织学分级Ⅱ级及Ⅲ级者肿瘤AR的阳性表达率分别为56.5％(61/108)及36.11％(13/36),Ⅰ级及Ⅲ级间比较差异有统计学意义(P =0.0031);AR表达差异与淋巴转移无相关性.AR在乳腺癌中的表达与ER的表达相关(P＜0.001),而与PR的表达无关(P=0.3280).结论 AR高表达的乳腺癌可能具有较好的预后.     

hRad17在浸润性乳腺癌中表达及其与细胞增殖、凋亡的关系

目的 探讨乳腺癌组织中hRad17表达及其与细胞增殖、凋亡之间的关系.方法 采用免疫组化SP法检测90例乳腺浸润性癌、8例乳腺原位癌及20例乳腺良性病变组织中hRad17表达.测定90例乳腺浸润性癌组织中Ki-67、微小染色体维持蛋白7(minichromosome maintenance proteins,MCM7)、Bcl-2、p53、ER、PR、c-erbB-2的表达.结果 hRad17蛋白在乳腺浸润性癌、乳腺原位癌和乳腺良性病变三组病例中表达差异有统计学意义(P<0.05).90例乳腺浸润性癌中,hRad17阳性表达56例(62.2%).乳腺浸润性癌的hRad17的阳性表达与乳腺癌的临床分期、组织学分级、淋巴结转移及Ki-67、MCM7、Bcl-2表达密切相关,与患者生存期呈负相关(P<0.05).hRad17的表达与患者年龄、肿块大小、组织学类型和p53、ER、PR、c-erbB-2表达均无关(P>0.05).结论 hRad17在乳腺癌中表达上调,提示在乳腺癌发生、发展中起重要作用.hRad17可成为判断乳腺癌预后新的分子标记物.     

乳腺癌组织中ERα mRNA和PR mRNA检测方法的建立和应用

建立测定雌激素受体α(ERα)mRNA和孕激素受体(PR)mRNA的实时荧光定量RT-PCR,探讨两者在乳腺癌组织及良性乳腺肿瘤组织中的表达水平。分别以pMD18 ERα和pMD18-PR质粒为定量模板,用循环阈值(Ct)定量起始模板,在荧光TaqMan方法的基础上建立了测定ERαmRNA和PR mRNA的实时荧光定量RT-PCR,并分别测定48例乳腺癌组织及28例良性乳腺肿瘤组织中ERαmRNA和PR mRNA的表达水平。ERαmRNA和PR mRNA测定的线性范围为10~3～10~8copy/μg RNA;ERαmRNA和PR mRNA高值和低值的批内和批间变异系数(CV)在5.07%～11.28%之间。ER mRNA在乳腺癌组织中的表达量为6.76×10~5copy/μg RNA(4.17×10~5,9.34×10~5),良性乳腺肿瘤组织中的含量为1.54×10~5 copy/μg RNA(1.02×10~5,2.06×10~5),乳腺癌组织的表达量高于良性组织(P<0.05);PR mRNA在乳腺癌组织中的表达量为1.02×10~6copy/μg RNA(6.81×10~5,1.36×10~6),良性乳腺肿瘤组织中的含量为4.93×10~5 copy/μg RNA(3.21×10~5,6.65×10~5),两者表达无明显差异(P>0.05)。ERαmRNA和PR mRNA在乳腺癌和良性乳腺肿瘤组织中的表达存在相关性。我们建立的测定ERαmRNA和PR mRNA的实时荧光定量RT PCR灵敏、稳定、重复性好,可供临床检测和研究。ERαmRNA和PR mRNA基因表达水平可作为预测治疗效果及判断预后的重要指标。     

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。     

乳腺癌中CD105表达及相关因素分析

目的 多项免疫组化（multiple immunohistoehemistry,MIHC）检测内皮因子CD105作为判断患者乳腺癌生物学行为及预后指标的可能性。方法 选取2003年11月-2004年1月经河北医科大学病理科确诊为原发性乳腺癌患者石蜡包埋组织标本87例,癌旁组织标本20例,同期乳腺良性病变标本24例。以CD105单克隆抗体为标记物进行免疫组化染色,根据CD105的表达水平计测微血管密度（mierovessel density,MVD）。结果CD105所标记的MVD在乳腺癌组织和乳腺良性病变以及乳腺良性病变与癌旁组织之间的表达差异均有显著性（P＜0．05）,癌旁组织中CD105几乎表达缺失;淋巴结转移阳性、组织分化差（Ⅲ级）、临床TNM分期晚以及VEGF表达阳性、ER、PR表达阴性的患者中,CD105的表达明显升高,差异均有显著性（P＜0．05）。结论 CD105主要在处于增殖状态的血管内皮细胞上表达,在标记肿瘤组织活性微血管方面特异性极高,是检测乳腺癌患者预后的重要指标。     

The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients

The secreted metastasis-inducing protein, human anterior gradient 2 (AGR2), has been independently reported to be associated with either a reduced or an increased survival of different groups of patients with breast cancer. We now aim to analyze the expression of AGR2 in a third completely independent group of patients using a specific AGR2 monoclonal antibody (mAb). Primary tumors from a group of 315 patients suffering from operable (stage I and II) breast cancer with 20-years follow-up were immunocytochemically stained with a specific mAb to AGR2 and associations with prognostic factors and patient survival were analyzed. The mAb specifically recognized AGR2 in Western blots, and positive staining for AGR2 was significantly associated with involved lymph nodes and staining for estrogen receptor α, progesterone receptor, and the metastasis-inducing proteins osteopontin, S100P, and S100A4. After 20 years of follow-up, only 26% of patients with AGR2-positive carcinomas survived compared with 96% of those with AGR2 negative carcinomas, with the highly significant difference in median survival times of 68 and >216 months, respectively (P < 0.0001). Cox’s multivariate regression analysis showed that staining for AGR2 was one of the most significant independent prognostic indicators, with a corrected relative risk of 9.4. The presence of AGR2 in the primary tumor is therefore a possible prognostic indicator of poor patient outcome in breast cancer.Anterior gradient 2 (AGR2) protein is a secreted protein first described in Xenopus laevis embryos, where it induces the formation of the forebrain and the mucus-secreting cement gland.¹ Human AGR2 is also found co-expressed with estrogen receptor α (ERα) in breast cancer cell lines² and its presence significantly correlates with ERα in breast carcinoma specimens.³ Subsequent studies have found elevated expression of AGR2 in adenocarcinomas of the esophagus, pancreas, prostate, and non-small cell lung cancer, showing that it is a widely overexpressed protein in human carcinomas.^{4,5,6,7,8,9,10} We have shown that human AGR2 is expressed at higher levels in malignant, rather than in benign breast tumors,¹¹ and that, when introduced in an expression vector into the benign, nonmetastatic rat mammary cell line, Rama 37,¹² it causes metastasis in syngeneic rats.¹¹ These results suggest that AGR2’s metastasis-inducing properties may contribute toward the malignant progression of some breast cancers. Certain molecules shown to induce metastasis in experimental breast cancer in rodents, for example, S100A4, S100P, and osteopontin (OPN),^13,14,15,16 provide a potential source for markers that may be useful as prognostic factors in predicting patient outcome in human breast cancer.Using a polyclonal antibody (PAb) to AGR2, a strong positive association was shown between AGR2 and ERα and between AGR2 and low histological grade in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy.¹⁷ In these patients, levels of AGR2 were also associated with a relatively poor outcome in patients with ERα-positive breast cancers after treatment with antiestrogen therapy.¹⁷ In contrast to these results, it has been reported that in another panel of 155 breast carcinoma patients treated with various adjuvant therapies, immunocytochemically detected AGR2 in the cancer cells was associated with significantly longer patient survival times, although there was still a significant correlation with the presence of ERα and lower tumor grade.¹⁸ To resolve these apparent conflicting associations of AGR2 protein with patient survival, the expression of immunocytochemically detectable AGR2 protein has now been determined in the primary tumors of an independent group of 315 patients suffering from operable breast cancer and treated by surgery alone with no accompanying adjuvant therapy. A new specific monoclonal antibody (mAb) to AGR2, which does not cross-react with the closely-related AGR3 protein,³ has been used to improve the accuracy of detection of AGR2. The results show that, in this large group of breast cancer patients, the presence of immunocytochemically detectable AGR2 protein in the primary tumor is strongly associated with a reduced survival of the corresponding patients.     

EGR-1、c-erbB-2、ER、PR在乳腺癌中的表达及其相互关系

目的：探讨早期生长反应基因（ＥＧＲ－１）在乳腺癌的表达及其与癌基因ｃ－ｅｒｂＢ－２和ＥＲ、ＰＲ的关系。方法：应用免疫组织化学ＳＡＢＣ法,以ＥＧＲ－１、ｃ－ｅｒｂＢ－２、ＥＲ、ＰＲ抗体标记７５例不同病变的乳腺组织。结果：乳奶性病变可见相对高水平的ＥＧＲ－１表达而乳腺癌ＥＧＲ－１阳性仅１９例（４２．２％）,ＥＧＲ－１表达与乳腺癌淋巴结转移和ＥＲ、ＰＲ表达有关（Ｐ〈０．０５,Ｐ〈０．０１）,与ｃ－ｅｒｂ     

乳腺癌bcl-2甲基化的检测及与表达、预后的关系

目的：建立bcl-2基因甲基化特异的PCR（MSP）检测方法，并探讨乳腺癌bcl-2甲基化与蛋白表达、预后因素（肿瘤大小，淋巴结转移，增殖细胞核抗原PCNA，雌、孕激素受体ER、PR情况）的关系。 方法： 设计bcl-2基因MSP引物，采用MSP方法检测54例乳腺癌bcl-2基因5’端启动子CpG岛甲基化状态。采用免疫组化S-P法检测54例乳腺癌bcl-2、PCNA、ER、PR的表达。 结果： 乳腺癌bcl-2甲基化率为29.6%。Bcl-2甲基化与其蛋白表达之间呈显著负相关（P＜0.01）。Bcl-2甲基化率高与不良的预后因素（PCNA标记指数LI高、ER-和PR-）显著相关（P＜0.01）。 结论： 该研究建立bcl-2基因MSP检测方法，MSP扩增和测序结果证实，bcl-2基因MSP引物设计是合理的。bcl-2甲基化有可能成为乳腺癌预后不良的分子检测指标。     

昼夜节律蛋白Cry2作为结直肠癌预后和化疗敏感性预测因子的研究

目的:检测Cry2在结直肠癌组织中的表达,探讨Cry2在结直肠癌预后和辅助化疗敏感性预测中的作用。方法:收集16名规律接受包含5-氟尿嘧啶的新辅助化疗的结直肠癌切除术患者,使用实体肿瘤疗效评估标准评估化疗疗效,并根据疗效分为完全反应(CR)/部分反应(PR)和病灶稳定(SD)/病灶进展(PD)组,免疫组化检测Cry2表达,评分后进行双侧x²检验。收集307名在2001年至2005年间接受结直肠癌切除术患者的肿瘤组织,制作组织芯片,免疫组化检测Cry2表达,用log-rank法进行单因素分析,用Cox回归模型进行多因素分析,用Kaplan-Meier法绘制生存曲线。结果:CR/PR组Cry2表达较低,SD/PD组Cry2表达较高,差异显著(P<0.05)。307例中Cry2高表达者84人,平均生存83.46月,Cry2低表达者223人,平均生存100.10月,两组间差异显著(P<0.05)。Cry2低表达者预后较好。307例结直肠癌切除术患者Cry2表达高低风险比为1.70,其95%置信区间为1.09~2.66,差异显著(P<0.05),Cry2的表达是影响预后的独立因素。16例接受化疗的结直肠癌切除术患者Cry2表达高低风险比为2.88,其95%置信区间为1.03~8.06,差异显著(P<0.05),Cry2的表达是影响化疗预后的独立因素。结论:根据Cry2表达高低可预测结直肠癌新辅助化疗的疗效,也可预测结直肠癌患者的预后。     

Angiopoietins 1 and 2 and Tie-2 receptor expression in human ductal breast disease

Staton C A, Hoh L, Baldwin A, Shaw L, Globe J, Cross S S, Reed M W & Brown N J
(2011) Histopathology 59 , 256–263 Angiopoietins 1 and 2 and Tie‐2 receptor expression in human ductal breast disease Aims: This study aimed to identify the involvement of the angiopoietin/Tie‐2 receptor system in breast cancer development, progression, metastasis and angiogenesis. Methods and results: We quantified and correlated angiopoietin‐1 (Ang‐1), Ang‐2 and Tie‐2 expression in sections of normal human breast, benign and premalignant hyperplastic tissue, pre‐invasive and invasive cancer, and compared these findings with our previously published data on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the same samples. A breast cancer tissue microarray was used to evaluate the prognostic value of these factors. Histological analysis revealed a significant decrease in Ang‐1 expression (P = 0.001) and an inverse correlation with MVD (r = ?0.442, P = 0.008) and VEGF (r = ?0.510, P = 0.002) in the non‐invasive lesions. In contrast Ang‐2 expression increased significantly (P = 0.0004) with increasing severity of lesion and correlated with MVD (r = 0.570; P = 0.0002), while Tie‐2 expression remained relatively unchanged. Expression of all three factors was reduced in invasive breast cancer and did not correlate with oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), lymph node status or tumour grade. Conclusions: These data suggest that a change in the angiopoietin balance in favour of Ang‐2 is associated with the angiogenic switch at the onset of hyperplasia in the breast. However, angiopoietins and the Tie‐2 receptor are not related to known prognostic indicators in invasive breast cancer.     

Immunophenotyping of male breast cancer

Kornegoor R, Verschuur‐Maes A H J, Buerger H, Hogenes M C, de Bruin P C, Oudejans J J, Hinrichs B & van Diest P J
(2012) Histopathology
Immunophenotyping of male breast cancer Aims: Male breast cancer is a rare disease, and knowledge of carcinogenesis is limited. Conflicting results, based on small series, have been reported for clinically relevant biomarkers. Methods and results: One hundred and thirty‐four cases of male breast cancer were immunohistochemically stained on tissue microarrays for oestrogen receptor (ER), progesterone receptor (PR), androgen receptor, human epidermal growth factor receptor 2 (HER2), BRST2, cyclin D1, bcl‐2, p53, p16, p21, Ki67, cytokeratin (CK) 5/6, CK14, and epidermal growth factor receptor. Data were correlated with clinicopathological features and patient outcome. High mitotic count and high grade were correlated with high Ki67, HER2 amplification/overexpression, p53 accumulation, high p21 expression, low PR expression, and low bcl‐2 expression. PR negativity (P = 0.009) and p53 accumulation (P = 0.042) were correlated with decreased 5‐year survival and were independent markers for patient outcome in Cox regression. In unsupervised hierarchical clustering, four groups were identified that were correlated with distinctive clinicopathological features. The hormone negative/ER‐positive/high‐grade cluster was significantly associated with decreased survival (P = 0.011) and was an independent prognostic factor in Cox regression. Conclusions: Several tissue biomarkers are associated with an aggressive phenotype in male breast cancer. PR and p53 are the most promising individual prognostic markers. On the basis of immunophenotype, four distinctive and prognostically relevant male breast cancer groups were identified, indicating that protein expression profiling may be clinically useful in male breast cancer.     

多项生物指标在乳腺癌中的表达及其关系与预后

目的 探讨多项生物学指标c-erbB-2,PCNA,P53,EGFR,nm23,ER,PR在乳腺癌中的表达与临床乳腺癌预后的关系及这些指标间的相互关系。方法 应用免疫组织化学方法对87例乳腺癌组织切片c-erbB-2,PCNA,P53,EGFR,nm23,ER,PR的表达进行检测。结果 乳腺癌远处转移率与腋淋巴结转移数目有关，c-erbB-2阳性率与肿瘤大小，临床分期正相关，PCNA阳性率与肿瘤大小，腋淋巴结转移数目正相关，P53与肿瘤大小正相关，c-erbB-2与PCNA，P53，EGFR，PR相关，P53与PR相关，ER与PR相关。结论 肿瘤大小，腋淋巴结转移数目，临床分期，c-erbB-2,PCNA,P53,PR等多指标联合应用有助于提高对乳腺癌预后评价的正确性。     

Cyclooxygenase 2 (COX2) expression is associated with poor outcome in ER-negative, but not ER-positive, breast cancer

AIMS: Inflammation and hormonal signalling induce cyclooxygenase 2 (COX2) expression in solid tumours. COX2 expression is linked to neovascularization and tumour growth. HER2 modulates colorectal cancer COX2 expression. We investigated interactions between COX2 and HER1-4 in breast cancer. METHODS AND RESULTS: COX2 expression was localized to epithelial cells with 21.2% of cases expressing higher levels than normal epithelium. Elevated COX2 expression was not associated with size, grade, high Nottingham prognostic index (NPI) or oestrogen receptor (ER) negativity. No association was observed between COX2 and HER1-4 expression. High COX2 expression was associated with reduced disease-free survival (P = 0.03) and disease-related survival in ER-negative (P = 0.046) but not ER-positive disease (P = 0.835). CONCLUSION: HER1, 2, 3 and 4 are not associated with high breast tumour COX2 expression. COX2 is frequently expressed in breast carcinoma cells and adjacent epithelium. COX2 may be an important factor in promoting tumour progression in ER-negative tumours and a potential drug target in breast tumours.     

Analysis of differentially expressed proteins between HER2 positive and triple negative breast cancer and their prognostic significance

Both triple negative breast cancer (TNBA) and HER2-positive breast cancer lack expression of estrogen receptor alpha (ER) and progesterone receptor (PR), while human epidermal growth factor receptor 2 (HER2) in TNBC is also negative. This study aimed to identify the differentially expressed proteins (DEPs) between TNBC and HER2-positive breast cancer and to improve understanding of their role in the prognosis of breast cancer. By analyzing the breast cancer data set in The Cancer Proteome Atlas (TCPA) database, 15 DEPs between TNBC and HER2-positive breast cancer were identified. GO and pathway enrichment analysis were performed on DEPs, and the protein–protein interaction (PPI) network was constructed. The overall survival (OS) analysis of the breast cancer protein dataset in the Kaplan-Meier plotter showed that low expression of ACC1 suggested a higher OS of HER2-positive breast cancer (HR = 5.34, P < 0.05) and TNBC (HR = 2.88, P < 0.05). And TNBC patients with high TBA1B (HR = 0.16, P < 0.01) or low INPP4B (HR = 3.47, P < 0.05) expression have a better prognosis. Our research provides new insights into the prognostic indicators of TNBC and HER2-positive breast cancer, which could be further studied.     

Diagnostic and prognostic potential of serum angiopoietin-2 expression in human breast cancer

Background: Accumulating evidence demonstrated a link of increased expression of Angiopoietin-2 (Ang-2) with invasive and metastatic phenotypes of various types of human cancers. However, until now, the serum level and its diagnostic and prognostic potential in breast cancer have not been investigated. Methods: Enzyme-linked immunosorbent assays were used to measure the levels of Ang-2. Sensitivity, specificity and area under curve (AUC) for serum Ang-2 levels were determined using receiver operator characteristic (ROC) analysis. Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. Prognostic relevance of each variable to overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox regression model. Results: Serum expression of Ang-2 in patients with breast cancer was significantly higher than healthy control group (3171 ± 1024 vs. 1800 ± 874 pg/ml, P < 0.0001). ROC curve analysis showed that at the optimal cut-off (2558.5 pg/ml), serum level of Ang-2 had a sensitivity of 78.3% and a specificity of 77.0% for distinguishing breast cancer patients from healthy controls with an area under the curve (AUC) of 0.836 (P < 0.001, 95% confidence interval: 0.787-0.885). The 5-year OS of high Ang-2 expression group was significantly shorter than that of low Ang-2 expression group (55.9% vs. 80.3%; P = 0.018). Moreover, the 5-year DFS of high Ang-2 expression group was also significantly shorter than that of low Ang-2 expression group (46.0% vs. 68.7%; P = 0.029). Conclusions: Our data indicate that serum Ang-2 level has potential value for early detection of breast cancer. Furthermore, Ang-2 has prognostic value in patients with breast cancer.