乳腺浸润性导管癌bcl-2、bax基因蛋白表达与预后的关系

目的：研究ｂｃｌ－２、ｂａｘ基因蛋白在乳腺浸润性导管癌中表达的相关性及和预后的关系。方法：应用免疫化学ＡＢＣ法检测乳腺浸润性导管癌组织ｂｃｌ－２、ｂａｘ基因蛋白的表达。结果：存活组ｂｃｌ－２基因蛋白阳性表达率（４６／６５）明显高于死亡组的ｂｃｌ－２阳性表达率（１２／３５），且ｂｃｌ－２基因蛋白表达与淋巴结转移和临床分期呈负相关关系；而ｂａｘ在死亡组的阳性率（３１／２６）较ｂｃｌ－２（－）ｂａｘ（＋     

乳腺浸润性导管癌及小叶癌与乳腺原位癌之间的定量比较

尽管乳腺肿瘤的组织学分级及鉴别诊断可以在常规的HE切片中进行,然而,这不可避免地会带有主观偏面性,故提出具有可重复性的肿瘤定量组织学评估具有重要意义[1,2].本研究拟在乳腺原位癌及浸润性癌中,进行定量形态学比较,并在伴有或缺乏侵袭性成分的原位癌癌变细胞间特征的比较,观察小叶癌和导管癌之间的差异.     

p16基因在乳腺浸润性导管癌中甲基化的研究

目的探讨p16基因启动子的甲基化与乳腺浸润性导管癌发生的关系。方法采用甲基化特异性聚合酶链反应法（MSP）,对42份乳腺浸润性导管癌组织和24份乳腺非癌组织进行p16基因甲基化检测。结果 42例乳腺癌中,18例检测到p16基因甲基化,甲基化率为42.9%;24例乳腺非癌组织中检测到2例（均为乳腺纤维腺瘤）甲基化,甲基化率为8.3%。p16基因启动子的甲基化率乳腺癌组与非癌组比较有显著性差异（χ2=8.619,P〈0.05）。结论 p16基因甲基化对乳腺浸润性导管癌的临床诊断具有一定指导意义。     

乳腺浸润性导管/小叶混合癌的临床病理特征和预后分析

目的:探讨乳腺浸润性导管/小叶混合癌（IDC-L）与浸润性小叶癌（ILC）及浸润性导管癌（IDC）临床病理特征以及预后的差异。方法:回顾性分析2009年1月至2015年12月上海交通大学乳腺癌数据库中有完整临床病理资料与随访资料的IDC-L、ILC与IDC患者的临床病理特征以及预后的差异。结果:共2 957例乳腺癌患者入组,其中IDC-L、ILC与IDC分别有109、177和2 671例。多因素分析显示,与IDC-L相比,IDC患者多中心病灶和脉管浸润较少,而HER2阳性和Ki-67高表达较多（P<0.05）;ILC患者发病年龄较大、脉管浸润较少（P<0.05）。IDC-L患者的5年无乳腺癌生存率（BCFI）（82.1% vs 90.7%,P=0.040）和总生存率（OS）（91.0% vs 94.4%,P=0.029）比IDC患者差;但与ILC患者（BCFI:84.1%,P=0.803,OS:92.6%,P=0.803）无明显差异。多因素生存分析显示,病理类型、肿瘤大小、淋巴结状态以及分子分型是影响患者BCFI和OS的独立因素（P<0.05）,IDC-L较IDC患者有较差的BCFI（HR=1.67,95%CI:1.02~2.70,P=0.042）及OS（HR=1.89,95%CI:1.04~3.45,P=0.037）。结论:IDC-L临床病理特征与ILC相似,但与IDC有较多不同;IDC-L预后劣于IDC,与ILC无明显差异,有待进一步研究证实。     

乳腺浸润性小叶癌

乳腺浸润性小叶癌(ILC)检出率偏低,通过本组20例分析发现ILC有其一定临床病理特征:(1)部分病人年龄较轻,40岁以下占35％,20％为双侧性;(2)肿瘤较大,平均4.8cm,切面边界不清,无坏死;(3)癌细胞大小较一致,核异型不明显,分裂像少见;(4)组织形态结构可分为单行线状型,小梁索状或融合实性巢状型,腺管型和混合型。以上各型中均可见其围绕正常或扩张导管呈靶环状排列;(5)40％肿瘤中尚能见原位小叶癌,45％的原发癌和35％转移灶内见少数癌细胞浆内有粘液分泌;(6)82.4%ILC有腋窝淋巴结转移,其中2例转移癌形态酷似恶性淋巴瘤。综合分析上述特点,可提高ILC检出水平。     

乳腺导管原位癌与浸润性导管癌染色体微卫星杂合性缺失的比较

目的:研究乳腺导管原位癌与浸润性导管癌染色体3p区域微卫星杂合性缺失(loss of heterozygosity,LOH)的发生情况.方法:选取本院2005年9月至2009年2月手术切除石蜡包埋的乳腺癌组织切块43例,应用激光显微切割技术留取组织中乳腺浸润性导管癌(invasive ductal type carci...     

基于生物信息学筛选胰腺导管腺癌关键基因

目的:利用生物信息学方法分析胰腺导管腺癌（PDAC）基因表达谱芯片并筛选关键基因。方法:从公共数据库基因表达数据库（GEO）中下载PDAC基因表达谱芯片GSE28735、GSE15471、GSE101448,共纳入108例PDAC样本和97例癌旁组织样本。应用R语言limma包和impute包筛选差异表达基因。利用DAVID数据库和在线分析工具Kobas分别对差异基因进行GO功能富集分析和KEGG通路富集分析。利用STRING数据库和Cytoscape软件构建差异蛋白互作网络并进一步筛选关键基因。结果:3个基因表达谱芯片共有161个差异表达基因（|log2 fold-change(FC)|>2,P<0.05）,包括54个上调基因,107个下调基因。GO功能富集分析显示差异基因与extracellular exosome、extracellular space、extracellular matrix organization密切相关。KEGG通路分析显示差异基因主要富集在protein digestion and absorption、ECM-receptor interaction和focal adhesion等通路。蛋白质相互作用网络图中显示节点最多的10个枢纽基因分别是ALB、COL11A1、COL3A1、FN1、EGF、COL1A1、MMP9、COL5A2、ITGA2、COL6A3。结论:筛选所得的10个关键基因可能在PDAC发生发展中发挥重要作用,有望成为PDAC诊断及治疗的生物学靶标,为进一步研究PDAC发生发展的分子机制提供了理论依据。     

乳腺浸润性导管癌的超声特征及其与分子分型的相关性

目的:研究乳腺浸润性导管癌的超声表现特征,分析其与临床病理参数的关系。方法:回顾分析我院2014年1月至2018年12月乳腺外科收治的110例乳腺浸润性导管癌患者临床资料。按照不同分子亚型分为Luminal 型、HER-2 过表达型及TN 型。观察不同亚型乳腺浸润性导管癌患者的超声征象并对比分析。结果:彩色多普勒超声检测显示,乳腺浸润性导管癌病例肿块多呈现为形态不规则、边缘毛刺、垂直生长,以内部回声无变化、无微钙化发生、血流分级2级、淋巴结转移、弹性评分≥3分为主。乳腺浸润性导管癌不同分子分型中超声征象形态、边缘、方位、内部回声、微钙化、血流分级、弹性评分组间差异具有统计学意义（P＜0.05）,淋巴结转移与否差异无统计学意义（P＞0.05）。Luminal 型多见于形态不规则、边缘毛刺、垂直生长;TN型多见于形态规则、边缘光整、平行生长;HER-2过表达型多肿块内部微钙化、弹性评分≥3分。不同分子分型组间两两比较,Luminal型和TN型超声征象边缘、方位组间具有统计学差异（P＜0.012 8）;HER-2型和TN型超声征象边缘组间具有统计学差异（P＜0.012 8）;Luminal型和HER-2型超声征象内部回声、微钙化及弹性评分组间具有统计学差异（P＜0.012 8）。结论:乳腺癌超声特征与其分子分型存在一定关系,超声特征可为其分子分型提供一定参考信息。     

PDGF-BB 在乳腺浸润性导管癌中的表达及其临床意义

目的:探讨PDGF-BB在乳腺浸润性导管癌中的表达及其与临床病理特征之间的关系。方法:收集2015年6月至2017年8月新疆医科大学第一附属医院经病理证实的乳腺浸润性导管癌80例,采用免疫组化方法检测癌组织及癌旁组织PDGF-BB表达状况,并分析其与临床病理特征关系。结果:乳腺浸润性导管癌组织中PDGF-BB表达明显高于癌旁组织（57.50% vs 13.75%,P<0.05）;PDGF-BB表达与淋巴结转移（P<0.05）和较高的pTNM分期有关（P<0.05）;而与年龄、月经状态、肿瘤直径、PR、ER、HER-2、有无术后复发转移等临床病理特征无关（P>0.05）。结论:PDGF-BB在乳腺浸润性导管癌的发生及进展中起重要作用,其预后价值仍需进一步评价。     

乳腺浸润性导管癌分子分型与临床特征的关系

目的探讨乳腺浸润性导管癌不同分子亚型的分布,并分析各分子亚型与临床特征的关系。方法收集2006年1月-2011年6月明确诊断为乳腺浸润性导管癌病例100例,根据雌激素受体（ER）、孕激素受体（PR）、表皮生长因子受体-2（HER-2）的表达情况划分为四型,进一步分析不同分子亚型与浸润性导管癌临床特征的关系。结果100例中Luminal A型所占比例最大为65%,7%为Luminal B型, Triple Negative型占17%,Her-2(+)型占11%。各分子亚型乳腺浸润性导管癌患者发病年龄主要集中在40~59岁之间,占73%,Luminal A型发病年龄主要集中在40~49岁,而其他三型主要分布于50~59岁,四型在不同年龄组的分布上差异有统计学意义（P＜0.05）;Luminal A型淋巴转移发生率仅为30.1%,而Luminal B型与Her-2(+)型淋巴转移发生率较高,分别为71.4%及63.6%,各分子亚型的腋窝淋巴结转移率有显著差异（P＜0.05）;病理组织学分级Ⅰ级中Luminal A型所占比例最高,而Triple Negative型主要以Ⅲ级为主,差异具有统计学意义（P＜0.05）。结论乳腺浸润性导管癌各分子亚型分布差异具有统计学意义,各分子亚型与其临床特征关系密切。     

Histological Factors Associated with Initial Bone Metastasis of Invasive Ductal Carcinoma of the Breast

Bone is one of the most common sites of recurrence of breast cancer. Therefore, it would be clinically very useful if breast cancers with a high probability of bone metastasis (BM) could be identified by histopathological examination of the primary lesions. To elucidate histological characteristics associated with predisposition to initial BM, we examined nine histopathological parameters in the primary lesions of 110 invasive ductal carcinomas (IDCs) of the breast with 0 to 3 regional node metastases. These cases had recurrence between 4 months and 10.1 years after the initial radical surgery. The first metastatic site was bone in 24 cases, whereas other sites were involved in 86 cases. IDCs growing in a strand growth pattern or with fibrotic focus (FF) had a significantly higher frequency of initial BM than those growing in a non-strand growth pattern or without FF, respectively. Strand growth pattern was a significant predictor of the initial BM in multivariate analysis. In all 54 IDCs that developed BM during the follow-up period, osteolytic metastasis was significantly more frequent in the group with FF than in that without FF. This study demonstrated that strand growth pattern and the presence of FF are significant histopathological factors associated with initial BM. The combination of those predictive factors along with prognostic factors may provide a useful approach to identify patients at high risk for initial BM, enabling early treatment for the recurrent cancer.     

Concurrent Invasive Ductal Carcinoma of the Breast and Malignant Follicular Lymphoma,Initially Suspected to Be Metastatic Breast Cancer: A Case Report

This report describes a case of a 40-year-old female patient with concurrent invasive ductal carcinoma of the breast and malignant follicular lymphoma, initially suspected to be metastatic breast cancer. During the initial evaluation of invasive ductal carcinoma of right breast, multiple lymphadenopathies were noted throughout the body on ultrasonography and positron emission tomography/computed tomography images. Clinically, metastatic breast cancer was suggested, and the patient was administered chemotherapy, including hormonal therapy. The breast cancer improved slightly, but the lymphadenopathies progressed and excisional biopsy of a cervical lymph node revealed malignant follicular lymphoma.     

mTOR和4EBPS在乳腺浸润性导管癌中的表达及意义

[目的]探讨mTOR和4EBPS在乳腺浸润性导管癌中的表达及意义。[方法]采用免疫组化SP法检测45例乳腺癌及癌旁正常组织中mTOR和4EBPS的表达。[结果]mTOR在乳腺癌中的阳性率为75.56%（34/45）,在正常乳腺组织中的阳性率为20.00%（9/45）,差异有显著性（P〈0.05）。mTOR表达与乳腺癌淋巴结转移明显相关（P〈0.05）。4EBPS在乳腺癌中的阳性率为31.11%（14/45）,在正常乳腺组织中的阳性率为95.56%（43/45）,差异有显著性（P〈0.05）。4EBPS表达与乳腺癌淋巴结转移无关（P〉0.05）。mTOR与4EBPS表达呈负相关（r=-0.614,P〈0.05）。[结论]mTOR和4EBPS在乳腺癌组织中的异常表达可能与乳腺癌的发生有关,且mTOR的异常表达可能与乳腺癌的转移有关。     

Bioinformatics Analysis Reveals Significant Genes and Pathways to Targetfor Oral Squamous Cell Carcinoma

Purpose: The purpose of our study was to explore the molecular mechanisms in the process of oral squamouscells carcinoma (OSCC) development. Method: We downloaded the affymetrix microarray data GSE31853 andidentified differentially expressed genes (DEGs) between OSCC and normal tissues. Then Gene Ontology (GO)and Protein-Protein interaction (PPI) networks analysis was conducted to investigate the DEGs at the functionlevel. Results: A total 372 DEGs with logFC| >1 and P value < 0.05 were obtained , including NNMT, BAX,MMP9 and VEGF. The enriched GO terms mainly were associated with the nucleoplasm, response to DNAdamage stimuli and DNA repair. PPI network analysis indicated that GMNN and TSPO were significant hubproteins and steroid biosynthesis and synthesis and degradation of ketone bodies were significantly dysregulatedpathways. Conclusion: It is concluded that the genes and pathways identified in our work may play critical rolesin OSCC development. Our data provides a comprehensive perspective to understand mechanisms underlyingOSCC and the significant genes (proteins) and pathways may be targets for therapy in the future.     

Identifying Differentially Expressed Genes and Screening Small Molecule Drugs for Lapatinib-resistance of Breast Cancer by a Bioinformatics Strategy

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor(EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positivebreast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers theuse of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistanceof breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials andMethods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474(lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentiallyexpressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses wereperformed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicalsthat reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enrichedin 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples.In addition, several small molecules were screened as the potential therapeutic agents capable of overcominglapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating themechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.     

A Proposal for a New Histological Classification Scheme for Predicting Short-term Tumor Recurrence and Death in Patients with Invasive Ductal Carcinoma of the Breast

Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.