乳腺浸润性导管癌的高频彩色多普勒超声诊断分析

分析了52例乳腺浸润性导管癌患者的彩色多普勒超声图像。对肿块的大小、形态、边缘、回声、钙化、毛刺征、腋下淋巴结肿大、血流分级、阻力指数进行统计,并用用SPSS12.0统计软件进行处理,P<0.05为有显著性差异。彩色多普勒超声声像图对乳腺浸润性导管癌具有临床诊断价值。     

B7-H4基因多态性与乳腺浸润性导管癌预后的相关性研究

目的探讨B7-H4基因rs10754339、rs10801935和rs3738414等单核苷酸多态性（SNP）位点多态性与黑龙江省妇女乳腺浸润性导管癌预后的相关性。方法取280例乳腺浸润性导管癌患者的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性（PCR．RFLP）技术进行B7．H4单核苷酸多态性检测,引用统计学软件分析基因多态性与患者临床指标（包括肿瘤大小,淋巴结转移,以及雌激素受体、孕激素受体和P53基因的表达）间的关系（卡方检验计算P值）,进而确定该基因与黑龙江省汉族妇女乳腺癌预后的相关性。结果B7-H4基因的rs10754339中,AA和AG基因型发生频率在雌激素受体表达阳性和阴性患者中有统计学差异（Х^2=4．06,P〈0．05;Х^2=3．97,P〈0．05）,AA基因型和G等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异（Х^2=4．74,P〈0．05;Х^2=5．30,P〈0．05）。rs10801935中,AA基因型和C等位基因发生频率在孕激素受体表达阳性和阴性患者中有显著差异（Х^2=5．36,P〈0．05;Х^2=5．90,P〈0．05）,而AC基因型发生频率在P53基因表达阳性和阴性患者中有显著差异（Х^2=5．82,P〈0．05）。结论B7-H4基因多态性与乳腺浸润性导管癌患者雌激素受体,孕激素受体及P53基因的表达有关联,与乳腺癌患者的预后有一定相关性。     

乳腺管状小叶癌E-cadherin／catenin的表达

管状小叶癌（tubulolobular carcinoma，TLC）是一种少见的乳腺癌类型，既往研究显示其临床类似小叶癌。该研究对19例TLC的临床病理特征进行了总结并与10例小管癌（Tubular carcinoma，TC）和10例小叶癌（lobular carcinoma．LC）进行了比较。该组TLC患者平均年龄61岁，其中2例有浸润性导管癌病史。TLC患者手术包括乳腺节段切除术（12／18例）、     

Dextroscope系统对乳腺浸润性导管癌的三维重建及术前应用

目的:研究Dextroscope系统对乳腺浸润性导管癌的三维重建方法,探讨其临床应用价值.方法:对浸润性导管癌10例患者采用Dextroscope系统软件生成虚拟图像,从任意角度观察肿瘤与乳腺的解剖关系,确定保乳手术方案并进行模拟操作.10例均行乳腺癌保乳手术.结果:Dextroscope系统对乳腺浸润性导管癌的三维重建图像清晰,可以精确定位肿瘤.10例患者病理切缘均为阴性.术后病理大体标本与术前模拟图像测量数值,差异无统计学意义(P＞0.05).结论:通过Dextroscope系统,术者提前预演手术,为精确手术创造了条件,对乳腺癌保乳手术的实施有指导意义.     

上皮钙依赖粘附素相关分子在乳腺浸润性小叶癌和导管癌中的表达及意义

目的 探讨上皮钙依赖粘附素相关分子α-、β-、γ-catenin在乳腺浸润性小叶癌（ILC）和浸润性导管癌（IDC）中的表达及其意义。方法 采用免疫组织化学LSAB法检测了19例ILC和32例IDC组织中α-、β-、γ-catenin的表达,并根据阳性癌细胞占肿瘤细胞的比例进行半定量化分析和统计学x^2检验。结果 α-、β-、γ-catenin在19例ILC中表达缺失和明显减少的分别为15例（78.9%),10例（52.6%)和16例（84.2%),而在32例IDC癌组织中的表达缺失和明显减少为24例（75.0%),14例（43.8%)和26例(81.3%)例。另外,这3种蛋白在浸润性癌组织中表达强度弱于原位癌灶的表达强度。α-catenin和β-catenin在乳腺浸润性癌中的表达具有明显的正相关性,未发现α-、β-、γ-catenin在乳腺浸润性癌中的表达与有无伴有淋巴结转移病例之间的关系有统计学意义。结论 α-、β-、γ-catenin在乳腺ILC和IDC中表达均为明显缺失和减少,说明这些粘附分子在乳腺浸润性癌发生中确实丧失了其正常的细胞粘附功能。     

超声鉴别诊断乳腺典型髓样癌与不典型髓样癌的价值分析

目的分析病理证实的乳腺髓样癌及不典型髓样癌的超声及病理资料,证明超声诊断乳腺髓样癌价值。方法回顾性分析114例乳腺髓样癌病灶病理资料,将其分为髓样癌组及不典型髓样癌组,分析其超声声像图中病灶的形态、大小、边缘、边界、内部回声、血流情况等,探讨两组超声声像图的差异。结果乳腺典型髓样癌病灶93例,不典型髓样癌病灶21例,两组的超声声像图上各特征均无明显统计学差异。超声诊断典型髓样癌和不典型髓样癌良恶性的准确性分别为83.87%、85.71%。结论超声对鉴别乳腺髓样癌良恶性方面具有诊断价值,但在鉴别髓样癌与不典型髓样癌方面价值有限。     

锰超氧化物歧化酶在乳腺浸润性导管癌中的表达及临床意义

目的检测锰超氧化物歧化酶(manganese superoxide dismutase,MnSOD)在乳腺浸润性导管癌组织及癌旁正常组织中的表达,探讨MnSOD在肿瘤的发生及肿瘤侵袭过程中的作用。方法采用RT-PCR和Western blot法分别对20例乳腺浸润性导管癌组织样本和20例癌旁正常组织样本的MnSOD mRNA及蛋白表达进行检测,以β-actin作为定量参考物,比较其在乳腺癌组织和癌旁正常组织中的表达差异,并结合临床特征淋巴结转移和TNM分期,分析MnSOD在肿瘤不同阶段表达的差异。结果乳腺浸润性导管癌组织MnSOD mRNA的表达值为0.61±0.15,癌旁组织为1.24±0.14,两者比较差异具有统计学意义(P<0.01);MnSOD蛋白在癌组织中表达值为0.40±0.04,癌旁组织为0.75±0.06,两者比较差异具有统计学意义(P<0.01)。乳腺浸润性导管癌中淋巴结转移与非淋巴结转移MnSOD mRNA及蛋白表达无统计学意义(P>0.05)。TNM分期:Ⅰ期4例MnSOD mRNA表达值为0.45±0.15,Ⅱ期9例MnSOD mRNA表达值为0.44±0.15,Ⅲ期7例MnSOD mRNA表达值为0.36±0.07,Ⅱ期与Ⅲ期及Ⅰ期与Ⅲ期的比较差异均有统计学意义(P<0.05);Ⅰ期与Ⅱ期比较差异无统计学意义(P>0.05);Ⅰ～Ⅲ期MnSOD蛋白表达三者相互间比较差异均无统计学意义(P>0.05)。结论乳腺浸润性导管癌组织中Mn-SOD mRNA和蛋白表达明显下降,检测MnSOD的表达可作为临床诊治及判定乳腺浸润性导管癌预后的指标。     

乳腺浸润性导管癌中N-cadherin mRNA及蛋白的表达与预后分析

目的 探讨N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的表达及其临床意义.方法 采用原位杂交技术和免疫组化SP法检测70例乳腺浸润性导管癌中N-cadherin mRNA及蛋白表达,以30例乳腺不典型导管增生为对照组.结果 乳腺浸润性导管癌中N-cadherin mRNA及蛋白阳性率分别为61.4%(43/70)、68.6%(48/70),乳腺不典型导管增生中N-cadherin mRNA及蛋白阳性率分别为3.3%(1/30)、6.7%(2/30),差异有统计学意义(P<0.01);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达与淋巴结转移、TNM分期以及ER、PR表达有关,差异有统计学意义(P均<0.01);与患者年龄、肿瘤大小和组织学分级无关(P均>0.05);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达呈正相关(rs=0.73,P<0.01);N-cadherin mRNA阳性患者生存率明显低于阴性患者,差异有统计学意义(P<0.01).结论 N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的过表达提示其对乳腺癌发生、发展、浸润及转移起重要作用,并提示患者预后不良.     

乳腺浸润性小叶癌的临床病理特征

目的：探讨乳腺浸润性小叶癌( invasive lobular carcinoma, ILC)的临床病理特征及其预后因素。方法回顾性分析98例ILC和530例乳腺非特殊型浸润性癌患者的临床病理资料,观察ILC的临床病理特征及其预后因素。结果 ILC和非特殊型浸润性癌的中位随访时间分别为68．5、67个月。与非特殊型浸润性癌相比,ILC患者就诊时年龄较大,肿瘤较大,组织学分级多为2级,ER、PR阳性率高,HER-2多为阴性,Ki-67增殖指数较低,分子分型多为管腔A型(P<0．001)。 ILC中,经典型ILC肿瘤较小,组织学分级较低,Ki-67增殖指数较低,分子分型中管腔A型较多;非经典型ILC中管腔B型、三阴型和HER-2过表达型较多(P=0．035)。单因素分析显示经典型与非经典型ILC的无病生存率和总生存率差异均有统计学意义(P=0．043,P=0．048);ILC与非特殊型浸润性癌的无病生存率和总生存率差异无统计学意义(P=0．537,P=0．397);多因素分析显示,ILC中管腔A型患者的总生存率明显高于三阴型和HER-2过表达型(P=0．016,P=0．015)。结论 ILC的预后和组织学分型与分子分型有关,应为预后较差的患者探寻新的治疗策略。     

ALDH1A1在乳腺浸润性导管癌中的表达及临床意义

目的探讨ALDH1A1在乳腺浸润性导管癌中的表达及临床意义。方法收集2004年至2008年在中国医科大学附属第一医院乳腺外科病房行根治性手术的158例有完整随访资料的乳腺浸润性导管癌组织石蜡标本,采用免疫组化SP法检测ALDH1A1蛋白在乳腺癌组织中的表达,分析其与临床病理因素及预后的关系。结果 ALDH1A1主要表达于细胞浆。乳腺癌浸润性导管癌组织中ALDH1A1表达阳性率为56.3%。乳腺癌浸润性导管癌组织中ALDH1A1的表达与年龄、绝经状态、肿瘤大小、临床分期、临床分级无关(P0.05),而与淋巴结转移相关(P=0.009)。ALDH1A1阳性表达患者无病生存时间(DFS)和总生存时间(OS)均短于ALDH1A1阳性表达患者,差异具有有统计学意义(P=0.022和P=0.011)。Cox比例风险回归分析显示ALDH1A1是影响乳腺浸润性导管癌患者预后的危险因素(P=0.025和P=0.014),但不是独立危险因素(P=0.892和P=0.489)。结论 ALDH1A1蛋白在乳腺浸润性导管癌的发生、发展中起一定作用,与淋巴结转移密切相关,可能是影响乳腺浸润性导管癌预后的重要指标。     

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women

Intending to clarify the true Incidence of Invasive lobular carcinoma of the breast In Japanese women as well as the frequency of unilateral multlcentriclty, 362 cases of clinically defined monocentrlc breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologlc types: Invasive lobular carcinoma (ILC) or Invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which Is more than In most previous Japanese studies. Unilateral multicentric breast carcinoma was detected In 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently In variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast In Japanese women is low and that unilateral multicentricity Is not significantly higher in ILC than in IDC.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

Signet Ring Cells in Breast Carcinoma

Two cases of breast carcinoma composed predominantly of neoplastic cells with a signet ring appearance, one a case of invasive lobular carcinoma (ILC) and the other a case of invasive ductal carcinoma (IDC), were examined electron microscopically and immunohistochemically. In signet ring cells in the ILC, mucin was demonstrated ultrastructur-ally in the intracytoplasmic lumina and also to a small degree in the cytoplasmic mucous granules, whereas in signet ring cells in the IDC, mucin was found only in the cytoplasmic mucous granules. Immunohistochemically, signet ring cells in the ILC were intensely positive for gross cystic disease fluid protein (GCDFP-15), but those in the IDC showed no immunoreaction for GCDFP-15. Thus ultrastructural features and GCDFP 15 immunoreactivity appear to be useful for distinguishing between the two different types of signet ring cells.     

DNA content of diffusely infiltrative carcinomas in the stomach

DNA content of diffusely infiltrative carcinomas of 15 Japanese patients, ranging in age from 38 to 65 years, was determined by cytofluorometry, using paraffin sections which were available for histological examination. Sections were stained with 0.0025% propidium iodide. By measuring the fluorescence intensity of at least 50 mitotic cells, ploidy patterns of the cancers were determined, whereas a control of the diploid DNA content was set by measuring the fluorescence intensity of mitotic cells in the non-cancerous gastric mucosa; only metaphase nuclei in the sections were considered to have a whole amount of nuclear DNA in the cytofluorometric measurement. In the present study, it was found that most of the diffusely infiltrative carcinomas consisted of a heteroploid cell line. Their stem DNA contents ranged between 2.8C and 4.8C (2C corresponds to a diploid amount of nuclear DNA). Of 15 cancers, four comprised a mosaic cancer of two different heteroploid cell lines. We encountered only one carcinoma containing a diploid cell line. However, this cancer also contained a heteroploid cell line. Six cancers contained a polyploid cell population, the DNA content of which was double of the stem DNA content. In most cases, the cancer cells distributed in the mucosal layer were also heteroploid, thereby suggesting a heteroploid origin of the diffusely infiltrative carcinomas.     

Clonal profiling of mixed lobular and ductal carcinoma revealed by multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization

A needle biopsy of a mass in the right breast of a 36‐year‐old woman revealed invasive ductal carcinoma (IDC), and approximately 20% of cancer cells showed unequivocal membranous staining with the HercepTest. After systemic therapy with trastuzumab and paclitaxel followed by FEC (fluorouracil + epirubicin + cyclophosphamide), a right mastectomy was performed. By histological and immunohistochemical examinations, the resected tumor consisted mainly of E‐cadherin‐negative invasive lobular carcinoma (ILC), and the rest was ERBB2‐positive IDC; thus, the diagnosis was mixed ductal and lobular carcinoma. Multiplex ligation‐dependent probe amplification and fluorescence in situ hybridization (FISH) analyses revealed that ILC and IDC shared high‐level amplification of CCND1 in homogeneously staining regions (HSR) and that IDC had an additional HSR‐type amplicon of ERBB2. These findings strongly indicate that IDC and ILC had a common precursor cell with CCND1 amplification. Review of the biopsy specimen with FISH showed IDC with gene amplifications of CCND1 and ERBB2 as a minor component, IDC without amplification of CCND1 or ERBB2 as a major component, and a minute portion of ILC with CCND1 amplification. We speculate that chemotherapy and trastuzumab caused a marked reduction in IDC; however, ILC with CCND1 amplification was resistant to chemotherapy and grew.     

Expression of autophagy related proteins in invasive lobular carcinoma: comparison to invasive ductal carcinoma

The aim of this study is to compare the expression of autophagy related proteins in invasive lobular carcinoma (ILC) with that of autophagy related proteins in invasive ductal carcinoma (IDC), and to determinate its implication. Tissue microarray containing 114 ILC and 692 IDC was constructed, and immunohistochemistry was performed for autophagy related protein (beclin-1, LC3A, LC3B, p62) and Ki-67. No significant difference in expression of autophagy-related proteins between pleomorphic type (n = 12) and classic type (n = 102) of ILC was observed, whereas ILC and IDC showed distinguished features that tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 were highly expressed in IDC and tumoral BNIP3 was highly expressed in ILC (P < 0.001). Beclin-1 expression was correlated with ER negativity (P = 0.016) and TNBC type (P = 0.024). BNIP3 expression was correlated with ER positivity (p = 0.040). Using multivariate Cox analysis, shorter overall survival was associated with tumoral beclin-1 positivity (hazard ratio: 21.19, 95% CI: 1.098-409.1, P = 0.043). In conclusion, ILC and IDC showed different expression pattern of autophagy-related proteins in tumor and stroma that demonstrated by higher expression of tumoral beclin-1, stromal LC3A, tumoral LC3B, tumoral p62 in IDC, and higher expression of tumoral BNIP3 in ILC.     

Expression of Sarcosine Metabolism-Related Proteins in Invasive Lobular Carcinoma: Comparison to Invasive Ductal Carcinoma

Purpose

The aims of this study were to compare the expression of sarcosine metabolism-related proteins between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) and to determine the implications of these results.

Materials and Methods

Tissue microarrays were constructed, containing 30 samples from normal breast tissue, 114 samples from patients with ILC, and 692 samples from patients with IDC. Immunohistochemical staining was performed to examine the expression of sarcosine metabolism-related proteins [glycine N-methyltransferase, sarcosine dehydrogenase, and l-pipecolic acid oxidase (PIPOX)].

Results

The sarcosine metabolic phenotype differed between ILC and IDC (p<0.001). In IDC, sarcosine metabolic phenotype was distributed as null type (61.7%)>low sarcosine type (30.4%)>high sarcosine type (5.0%)>intermediate type (2.9%). However, in ILC, the sarcosine metabolic phenotype was distributed as low sarcosine type (61.4%)>null type (32.5%)>intermediate type (5.3%)>high sarcosine type (0.9%). PIPOX showed higher expression in ILC than in IDC (p<0.001) and correlated with androgen receptor (AR) positivity (p=0.001) in ILC.

Conclusion

Expression of sarcosine metabolism-related proteins differed between ILC and IDC. Low sarcosine type was the majority sarcosine metabolic phenotype of ILC. PIPOX expression was predominant in ILC and correlated with AR positivity.     

乳腺典型髓样癌与非典型髓样癌的超声诊断分析

目的探讨高频彩色多普勒超声对乳腺髓样癌的诊断价值。方法 56例乳腺髓样癌患者,均为女性,年龄25～87岁,平均年龄50.92岁;其中典型髓样癌35例,非典型髓样癌21例。患者手术前行乳腺超声检查,先用灰阶超声观察肿块的部位、大小、形态、边界、内部回声、有无钙化、后方回声增强或衰减,再启用彩色多普勒血流显像(CDFI)检查肿块的血流信号,频谱多普勒分析肿块血流阻力指数(RI),最后检查腋窝淋巴结有无肿大。结果乳腺髓样癌发生于左侧乳腺者占57.14%,高于右侧乳腺的42.86%,但差异无统计学意义(P>0.05)。典型髓样癌最大径平均值为2.39cm,略小于非典型髓样癌的2.52cm(P>0.05)。与非典型髓样癌比较,典型髓样癌形态较规则、边界较清楚、内部回声较均匀,多伴后方回声增强,钙化较少见。乳腺髓样癌血液供应多较丰富,该组32例典型髓样癌、18例非典型髓样癌进行了CDFI检查,血流Ⅱ/Ⅲ级者分别占65.63%、61.11%(P>0.05),其中20例进行了多普勒频谱分析,RI>0.70。结论典型髓样癌与非典型髓样癌在肿块的边界、回声均匀与否,有无钙化及后方回声增强等超声表现明显不同,术前高频彩色多普勒超声检查具有重要诊断价值。     

Histopathological and clonal study of combined lobular and ductal carcinoma of the breast

Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty‐two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re‐examination using immunostain of E‐cadherin and β‐catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation‐specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.