层粘连蛋白和纤维粘性蛋白在进展期胃癌组织中表达的研究进展

胃癌是我国常见的恶性肿瘤之一,其发病率和病死率均较高。近年研究证明恶性肿瘤的死亡原因关键是癌组织的浸润与转移,是癌细胞与细胞外基质(ECM)相互作用的结果。层粘连蛋白(laminin,IN)、纤维粘连蛋白(fibronectin,IN)是细胞外基质的重要组成成分,是一种大分子非胶原糖蛋     

血清层粘连蛋白的临床应用价值

 为探讨血清层粘连蛋白对良恶性肿瘤的诊断价值,我们检测了各类肝病及肿瘤患者的血清层粘连蛋白,其结果肿瘤患者较肝病患者高,肝病患者较健康者高,有显著差异（P＜0.01）我们认为：检测血清层粘连蛋白对良恶性肿瘤的诊断和治疗具有重要价值。     

乳腺癌PCNA表达及临床病理意义

目的：研究PCNA在乳腺癌表达的临床病理意义及其与ER,PR,C-erbB-2蛋白,nm23蛋白表达的相互关系。方法：应用微波修复免疫组化技术S－P法检测了82例乳腺癌中单克隆抗体PCNA的表达。结果：PCNA表达位于核中,乳腺癌中PCNA过表达率为48．78％（40／82）,其过表达与组织低分化,临床分期晚,有淋巴结转移及复发生存期短相关。与病人年龄,肿瘤大小,ER,PR,C－erbB-2蛋白,nm23蛋白表达无关。结论 ：PCNA过表达情况可作为反映乳腺癌低分化及预后差的单独指标。     

乳腺癌耐药蛋白在乳腺癌组织中的表达及其与预后的关系

目的:研究乳腺癌耐药蛋白(BCRP)在乳腺癌组织中的表达,评估其在乳腺癌预后中的作用。方法:采用免疫组织化学方法(IHC)检测60例手术切除的乳腺癌组织中BCRP的表达,并分析其与临床病理特征的关系及对预后的影响。结果:①BCRP在乳腺癌组织中的阳性表达率为35%(21/60例);②腋淋巴结或激素受体阳性者BCRP表达水平显著高于腋淋巴结阴性者和激素受体阴性者(P<0.05),BCRP表达与年龄、月经状况、肿瘤大小和组织学分级均无关(P>0.05);③Kaplan-Meier生存分析结果表明BCRP表达与无病生存期显著相关(P<0.05),但和总生存期无关(P>0.05);④Cox单因素和多因素分析都显示肿瘤大小、淋巴结转移和雌激素受体(ER)与无病生存期和总生存期显著相关(P<0.05),另外孕激素受体与总生存期(P<0.05)显著相关。结论:BCRP在乳腺癌组织中具有一定的表达水平,与乳腺癌患者的无病生存期有关,而与总生存期无关。     

乳腺癌组织中 Wnt5a 蛋白的表达与临床病理参数及预后的关系

目的：观察 Wnt5a 蛋白在乳腺癌组织中的表达情况,并分析其与乳腺癌相关临床病理参数的关系,初步探讨 Wnt5a 蛋白在人乳腺癌发生、发展过程中的作用。方法采用免疫组化 S-P 法检测80例乳腺浸润性导管癌组织及相应癌旁组织中 Wnt5a 蛋白的表达。结果 Wnt5a 蛋白在乳腺癌和癌旁组织中的阳性表达率分别为33.8%（27/80）和63.8%（51/80）,差异有统计学意义（P <0.05）;乳腺癌组织中 Wnt5a 蛋白的表达与淋巴结转移、TNM 分期有关（P <0.05）;与 ER 和 PR 的表达呈正相关（rs =0.294、0.316,P <0.05）。结论乳腺癌组织中 Wnt5a 蛋白的表达减少,提示其在乳腺癌发生、发展中发挥重要作用,有可能成为乳腺癌早期诊断和预后判断的指标及治疗的新靶点。     

肝癌细胞 67kDa层粘连蛋白受体的表达

背景与目的:本实验室最近发现人肝癌细胞 SMMC-7721表达的 67kDa层粘连蛋白受体( 67kDa Laminin receptor,67LR)与层粘连蛋白的结合能力明显高于正常肝细胞 L-02表达的 67LR,而 67LR在肝癌细胞和正常肝细胞中的表达水平尚不清楚.本研究旨在探讨 67LR在肝癌细胞中的表达,及其与层粘连蛋白结合能力的关系.方法:以人肝癌细胞 SMMC-7721、 HepG2和正常肝细胞 L-02为材料,采用 131I标记的层粘连蛋白测定其与细胞的结合能力;采用流式细胞术和 RT-PCR分析 67LR蛋白和 mRNA的表达水平. 结果: (1)相同条件下 SMMC-7721、 HepG2 细胞与层粘连蛋白特异结合量分别为 (17.54± 0.49) ng/105 cell、 (11.18± 0.53) ng/105 cell,而 L-02细胞的特异结合量为 (8.36± 0.48) ng/105 cell,表明肝癌细胞与层粘连蛋白的结合能力明显高于正常肝细胞( P< 0.01) ;(2)流式细胞术分析, SMMC-7721细胞的 67LR阳性表达率为 34.7%, L-02细胞的 67LR阳性表达率为 55.3%,而 HepG2 细胞则几乎不表达 67LR; (3)RT-PCR产物进行半定量分析发现,两株肝癌细胞的 67LR mRNA表达水平明显高于 L-02细胞.结论:肝癌细胞与层粘连蛋白的结合能力明显高于正常肝细胞 L-02,而细胞膜表面的 67LR水平却低于 L-02细胞,提示 SMMC-7721细胞 67LR的亲和力可能高于 L-02细胞,而且还涉及其它层粘连蛋白受体.     

p-ERK1/2、CD34、层粘连蛋白在乳腺癌组织中的表达及其意义

目的 探讨p-ERK1/2、CD34、层粘连蛋白(LN)在乳腺癌中的表达及其意义.方法 收集乳腺癌患者肿瘤组织蜡块76例,行免疫组化染色,检测乳腺癌患者癌组织标本中p-ERK1/2的表达水平,分析p-ERK1/2水平与其临床病理因素及CD34、LN的相关性.结果 p-ERK1/2、CD34、LN在乳腺癌组织中的表达水平与肿瘤TNM分期显著相关.CD34在乳腺癌组织中广泛表达,与p-ERK1/2水平正相关.LN在乳腺癌组织中表达与TNM分期及p-ERK1/2水平均呈负相关.结论 ERK通路异常活化与乳腺癌生长和浸润有关,可能参与了乳腺癌的发展过程,ERK通路可能通过促进血管生成及降解基底膜发挥促进乳腺癌进展的作用.     

食管鳞癌层粘连蛋白表达的意义

应用兔抗鼠层粘连蛋白抗体、ＰＡＰ免疫组化方法研究８０例食管鳞癌层粘连蛋白的表达结果显示：癌旁正常上皮、单纯性增生及不典型增生上皮层粘连蛋白均呈连续线状，原位癌呈线状，但可见局部中断，浸润癌层粘连蛋白表达呈多种形式；分化好的团块型及网状型在癌巢周围呈线状，但呈明显不规则和不连续，分化差的细索型癌则常呈碎片状，在癌浸润前缘有时见不定形阳性物质堆积。分析层粘连蛋白表达癌的分级，血管、神经侵犯及淋巴结转移     

纤维粘连蛋白在乳腺癌中的表达及与淋巴结转移的关系

目的 研究纤维粘连蛋白（ＦＮ）在乳腺浸润性癌中的表达及其与同侧腋窝淋巴结转移的关系。方法 应用免疫组化（ＳＰ）法检测５０例浸润性癌底膜及间质ＦＮ的表达。结果 癌巢周围基底膜ＦＮ的表达与癌细胞分化程度及淋巴结转移有关,而间质ＦＮ的表达与以上二者均无关,结论癌巢周围基底膜ＦＮ的表达对乳腺癌预后的评估有意义。     

MMP-9和层粘连蛋白受体在乳腺癌组织中的表达及其与转移和预后的关系

背景与目的:以往对乳腺癌细胞外基质与肿瘤转移及患者预后之间关系的研究尚少,且结论不一。本研究探讨乳腺癌组织中基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)及层粘连蛋白受体(lamininreceptor,LM-R)表达与肿瘤转移及患者预后的关系。方法:应用免疫组化方法检测80例乳腺癌组织及10例乳腺增生病组织中MMP-9、LM-R的表达,并用计算机图像分析系统测定表达的吸光度值。采用t检验、方差分析及相关分析方法分析它们与肿瘤转移和患者预后的关系。结果:乳腺癌组织中MMP-9表达显著高于乳腺增生病(t=8.87,P<0.05);在乳腺增生病组织中,LM-R表达于基底膜及部分腺泡和导管的腔缘,在乳腺癌组织中表达于细胞质及胞膜;17例癌间质血管基底膜有LM-R表达的癌组织中,LM-R表达高于血管基底膜无LM-R表达组(t=2.02,P<0.05);LM-R表达与组织学分级有关,分化低者,表达水平高(F=3.27,P<0.05);MMP-9及LM-R表达均与淋巴结转移有关,它们在有3个以上淋巴结转移组的表达低于3个以下及无转移组(tMMP-9=3.42,tLM-R=4.31,P<0.05),原发灶与转移灶的表达呈正相关(rMMP-9=0.654,rLM-R=0.755,P<0.001);MMP-9与孕激素受体负相关性(r=-0.363,P<0.05);MMP-9与LM-R之间呈正相关(r=0.503,P<0.01)。MMP-9及LM-R表达在生存3年以上组低于3年以     

Clinicopathologic Implications of EpCAM and Sox2 Expression in Breast Cancer

BackgroundThe purpose of this study was to investigate the clinicopathologic significance of EpCAM and Sox2 expression in breast cancer and to study their correlation during breast cancer progression.Patients and MethodsEpCAm and Sox2 expression were assessed using immunohistochemistry in ductal carcinoma insitu (DCIS), invasive breast cancer (IBC) and matched lymph node metastasis (LNM), if present.ResultsEpCAM overexpression was found in 63.2% of DCIS, 72.2% of IBC and 74.4% of LNM. In IBC cases, EpCAM overexpression was associated with high grade (P < .001), large tumor size (P = .051), poor Nottingham Prognostic Index (NPI) (P = .006), histological tumor types (P = .044) and the triple negative phenotype (P = .008). LNM frequently reflected the expression phenotype of the matched primary tumors with no significant differences between LNM and their primary tumors (P = .564). Sox2 expression was detected in 47.4%, 33.3% and 54.7% of DCIS, IBC and LNM respectively. In DCIS group, Sox2 expression was significantly associated with comedo type (P = .037), negative ER (P = .012) and PR (P = .037) and the triple negative phenotype (P = .006). In IBC cases, Sox2 expression showed significant associations with high grade (P = .045), nodal spread (P = .037), poor NPI (P = .018) and the triple negative phenotype (P < .001). LNM showed significantly higher Sox2 expression rates than primary tumors (P < .001). Significant positive associations between EpCAM overexpression and Sox2 positivity in DCIS (P = .027), IBC (P = .001) and LNM (P < .001) were found.ConclusionThis study emphasized the potential role of EpCAM and Sox2 in breast carcinogenesis and revealed their involvement during breast cancer progression and LN metastases.     

Hormone Receptor Expression and Clinicopathologic Features in Male and Female Breast Cancer

Background: Male and female breast cancers were investigated for variation in the clinicopathologiccharacteristics and expression of steroid hormone receptors in the northeast of Iran. Materials and Methods:Tumor specimens of 17 males and 338 females with breast cancer were collected at the hospitals of MashhadUniversity of Medical Sciences. Immunohistochemical expression of hormone receptors and clinicopathologicfeatures of breast cancer were compared between two groups. Results: The mean age in men was 15 years higherthan women (p=0.000). Males and females were mainly in stage II and III respectively (p=0.007). Although morethan 60% of male and female patients were grade II, the respective figures for grade I and III were 25% and12.5% in men but 7.1% and 27.2% in women respectively (p=0.025). ER was significantly more positive in menagainst women; 82.3% versus 53.4% (p=0.016). The related measures for PR was 58.8% and 50.3%, respectively(p=0.424). Males also showed significantly more ER expression than postmenopausal females; 82.3% versus48.9% (p=0.010). Conclusions: Breast cancer in males and females contrasted in age at diagnosis, histologicaltype, stage, grade and ER expression which emphasize they are separate diseases with different behaviors.     

19例男性乳腺癌临床病理分析

目的分析男性乳腺癌（MBC）的临床病理特征和影响预后的因素。方法对19例MBC患者临床病理资料进行回顾性分析。结果MBC发病率低,发病年龄大,病程长,病理类型多为浸润性导管癌,易见淋巴结转移。19例MBC患者中PR阳性率为63．16％（12／19）,ER阳性率为73．68％（14／19）,Her-2阳性率为21．05％（4／19）,Ki-67阳性率≥25％者为63．16％（12／19）。结论MBC较少见,多见于老年人,多为浸润性导管癌,且易经淋巴系统转移,且具有一定的性激素表达水平,应采取内分泌治疗。     

Clinicopathologic Characteristics of Breast Cancer in Jamaica

Breast cancer is the most common cancer in Jamaican women. This study assessed the clinicopathologicfeatures of cases in a hospital-based specialist clinic in Kingston, Jamaica. A retrospective chart review wasperformed for the 2-year study period and relevant clinical and surgico-pathologic data were recorded andanalyzed. Median age of the 121 breast cancer patients was 52 years (range 22-84, IQR 20) and there was 1 caseof male breast cancer. Most patients (65%) were referred from the surgical service after definitive breast cancersurgery, 20% were referred for pre-operative systemic therapy, and 15% had a diagnosis of metastatic disease.The surgico-pathologic group comprised 78 women who were referred for adjuvant therapy. The majorityhad presented with a palpable breast lump (91%), with median tumour size 3.5cm (range 0.4-13, IQR 4). Mosttumours were node positive (56%). Approximately one-third of patients had stage III disease (33%). Most womenpresented with large palpable tumours and had lymph node involvement confirmed on surgicopathologicalevaluation, indicative of limited early breast cancer detection. A national screening mammography programmeis recommended for detection of earlier lesions. Pre-operative systemic therapy should be considered as an optionfor eligible patients.     

AR在不同ER状态乳腺癌中的表达及临床病理意义

  目的  探讨雄激素受体（AR）在不同雌激素受体（ER）状态乳腺癌中的表达与临床病理特征间的关系及预后。  方法  从乳腺浸润性导管癌ER阳性和阴性病例中分别随机选取111例（ER+组）与113例（ER-组）,共计224例。采用免疫组化方法检测AR、ER、PR、HER-2、Ki-67、P53表达,对不同ER状态乳腺癌中AR表达与临床病理资料及预后因素进行分析。  结果  AR在浸润性导管癌中的阳性表达率为67.9%（152/224）,ER+组和ER-组分别为80.2%（89/111）、55.8%（63/113）。ER+组中AR的表达与肿瘤大小、组织学分级、pTNM分期和有无淋巴结转移相关（P < 0.05）;在ER-组中AR的表达与组织学分级、HER-2表达、绝经状态相关（P < 0.05）。单因素生存分析显示在ER+组和ER-组AR阳性者均具有较好的预后（P < 0.001,P=0.046）,Cox多因素回归分析显示在ER+组AR表达可作为影响无瘤生存的独立因素。  结论  AR可以作为指导临床内分泌治疗新的靶标,为不同ER状态乳腺癌激素治疗提供依据。      

1156例乳腺癌临床及病理分析

[目的]分析乳腺癌的临床及病理情况,以提高临床诊治水平.[方法]收集1156例乳腺癌手术病例及病理对照资料并进行分析.[结果]Ⅰ、Ⅱ期乳腺癌占57.6%,Ⅲ期乳腺癌占37.8%;肿瘤发生于外上象限者占48.5%;30～40岁、40～50岁、50～60岁年龄组均约占25%左右;切除淋巴结中28%有癌细胞转移.病理类型仍以浸润性导管癌为主,约占85%左右.[结论]早期乳腺癌比例大,为保乳手术提供了基础;乳腺癌患病年龄有提前趋势;特殊类型乳腺癌诊断及治疗仍是难点;发生部位及病理类型无明显变化.     

Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression

Purpose

Breast cancer displays varying molecular and clinical features. The ability to form breast tumors has been shown by several studies with aldehyde dehydrogenase 1 (ALDH1) positive cells. The aim of this study is to investigate the association between ALDH1 expression and clinicopathologic characteristics of invasive ductal carcinoma.

Methods

We investigated breast cancer tissues for the prevalence of ALDH1⁺ tumor cells and their prognostic value. The present study included paraffin-embedded tissues of 70 patients with or without recurrences. We applied immunohistochemical staining for the detection of ALDH1⁺ cells. Analysis of the association of clinical outcomes and molecular subtype with marker status was conducted.

Results

ALDH1⁺ and ALDH1^- tumors were more frequent in triple-negative breast cancers and in luminal A breast cancers, respectively (p<0.01). ALDH1 expression was found to exert significant impact on disease free survival (DFS) (ALDH1⁺ vs. ALDH1^-, 53.1±6.7 months vs. 79.2±4.7 months; p=0.03) and overall survival (OS) (ALDH1⁺ vs. ALDH1^-, 68.5±4.7 months vs. 95.3±1.1 months; p<0.01). In triple-negative breast cancer (TNBC) patients, DFS and OS showed no statistical differences according to ALDH1 expression (ALDH1⁺ vs. ALDH1^-, 45.3±9.4 months vs. 81.3±7.4 months, p=0.52; 69.0±7.5 months vs. 91.3±6.3 months, p=0.67). However, non-TNBC patients showed significant OS difference between ALDH1⁺ and ALDH1^- tumors (ALDH1⁺ vs. ALDH1^-, 77.6±3.6 months vs. 98.0±1.0 months; p=0.04) with no statistical difference of DFS (ALDH1⁺ vs. ALDH1^-, 60.5±8.0 months vs. 81.8±4.6 months; p=0.27).

Conclusion

Our findings suggest that the expression of ALDH1 in breast cancer may be associated with TNBC and poor clinical outcomes. On the basis of our findings, we propose that ALDH1 expression in breast cancer could be correlated with poor prognosis, and may contribute to a more aggressive cancer phenotype.     

三阴性乳腺癌临床病理特点及与EGFR表达关系的探讨*

目的:研究三阴性乳腺癌的临床病理特点、预后及与EGFR 表达的关系。方法:回顾性分析天津医科大学总医院1997年1 月至2004年1 月200 例乳腺癌患者的临床资料,总结其病理特征及随访结果,并将200 例病例对应的石蜡标本制作成组织芯片,用免疫组织化学法检测乳腺癌组织中ER、PR、HER-2 的表达,进行乳腺癌分子分型。检测EGFR 蛋白的表达,分析其与乳腺癌病理特征及预后的关系。结果:200 例乳腺癌患者中三阴性乳腺癌42例（21.00%）,在患者年龄、肿瘤大小、临床分期、淋巴结状态等病理参数的分析中,三阴性乳腺癌与非三阴性乳腺癌的分布无明显差异,而在绝经状态及肿瘤组织学分级的分析中,三阴性乳腺癌与非三阴性乳腺癌差异有统计学意义（P<0.05）。 三阴性乳腺癌患者中17例死亡（生存率59.52%）,非三阴性患者26例死亡（生存率83.54%）,二者有显著性差异（P<0.05）。 EGFR 在三阴性乳腺癌中表达率较高（69.05%）,与肿瘤组织学分级及淋巴结转移密切相关,且表达EGFR 的三阴性乳腺癌患者生存时间较短。结论:三阴性乳腺癌发病率虽然不高,但其与常规的乳腺癌预后相关因素缺乏特定联系,患者预后差。EGFR 在三阴性乳腺癌中高表达,可作为三阴性乳腺癌的一个重要的预后指标,并为临床提供了治疗的靶点。      

三阴型乳腺癌159例临床病理特征分析

目的探讨三阴型乳腺癌的临床病理特征。方法选取2003年3月～2003年11月手术切除并经病理检查证实的女性原发性乳腺癌747例。根据ER、PR、Her-2免疫组织化学表达情况,将747例乳腺癌分为2组,即ER、PR、Her-2蛋白均为阴性的三阴型乳腺癌和非三阴型乳腺癌。比较2组乳腺癌的临床病理特征。结果 747例乳腺癌病例中,159例为三阴型乳腺癌[ER（-）、PR（-）、Her-2（-）],占21.3%。2组乳腺癌在组织学分级上差异有统计学意义（P〈0.05）,三阴型组的组织学Ⅲ级占比高于非三阴型组。三阴型乳腺癌复发转移率高于非三阴型乳腺癌,但无统计学差异（P=0.236）。结论三阴型乳腺癌较非三阴型乳腺癌病理恶性程度高,预后更差。