食管癌幽门螺杆菌L型感染与其血管形成的关系

目的探讨食管癌Hp-L型(即球形:Hp)感染与肿瘤血管形成的相关性及Hp-L型对食管癌生长、侵袭和转移等生物学行为的影响。方法应用革兰染色、电镜和免疫组化ABC法,检测98例食管癌和30例对照组(食管癌切缘正常组织)的Hp-L型;用免疫组化SP法检测上述组织的微血管密度(MVD)值和血管内皮生长因子(VEGF)、p53表达,分析Hp-L型与MVD、VEGF、p53表达以及临床病理因素的关系。结果 食管癌组的Hp-L型阳性率为60.2％。电镜下组织中的Hp-L型有两种类型,可位于癌细胞间或癌细胞胞浆。食管癌组的Hp-L型阳性率、MVD值以及VEGF、p53表达阳性率均高于对照组(P<0.005～0.001),食管癌组中Hp-L型阳性组的MVD值、VEGF和p53表达阳性率也高于其Hp-L型阴性组(P<0.005～0.001)。Hp-L型阳性与MVD呈正相关(r=0.46,P<0.01),与VEGF、p53表达呈正相关(r=0.31,P<0.01)。食管癌组的Hp-L型阳性数与癌细胞的血管侵袭、侵袭深度、食管旁淋巴结转移及远处淋巴结转移相关,而与肿瘤大小无关。结论 Hp-L型与食管癌的血管形成密切相关,是影响食管癌生长、侵袭和转移的重要因素之一。     

幽门螺杆菌L型感染对食管癌MVD、VEGF、P53表达及肿瘤生物学行为的影响

目的 :探讨幽门螺杆菌L型(Hp_L,即球形Hp)感染与食管癌MVD、VEGF、P53表达的相关性及Hp_L对食管癌生长、浸润和转移等生物学行为的影响。 方法 :用革兰染色和免疫组化ABC法 ,检测98例食管癌和30例对照组的Hp_L;用免疫组化SP法检测上述组织的MVD值和VEGF、P53表达 ,分析Hp_L与MVD(微血管密度)、VEGF(血管内皮生长因子)和P53表达以及临床病理因素的关系。 结果 :癌组的Hp_L阳性率、MVD值以及VEGF、P53表达阳性率均高于正常组(P<0.005～P<0.001) ;癌组中Hp_L阳性组的MVD值、VEGF和P53表达阳性率也高于其Hp_L阴性组(P<0.005～P<0.001) ;Hp_L阳性与MVD呈正相关(r=0.46,P<0.01) ,与VEGF和P53表达呈正相关(r=0.31,P<0.01)。癌组的Hp_L阳性数与癌细胞的血管侵袭、浸润深度、食管旁淋巴结转移及远处淋巴结转移相关 ,而与肿瘤大小无关。 结论 :Hp_L与食管癌的新生血管形成密切相关 ,是影响食管癌生长、浸润、转移等生物学行为的重要因素之一     

乳腺癌组织p53和nm23及VEGF表达相关性的研究

目的:探讨p53、nm23基因和血管内皮生长因子(VEGF)在乳腺癌微血管生成及转移中的作用.方法:通过免疫组化SP法对64例乳腺癌标本中p53、nm23蛋白、VEGF及CD34抗体进行了检测.结果:乳腺癌组织中p53、nm23蛋白及VEGF的阳性表达率分别为65.63%、53.12%和68.75%.p53蛋白表达和VEGF有一致性,呈正相关,P<0.01.在有淋巴结转移的肿瘤中p53蛋白和VEGF阳性表达率及微血管密度(MVD)明显高于非转移组,P<0.05.nm23基因和VEGF在乳腺癌标本中无一致性和直接相关性,在nm23基因表达阴性和VEGF阳性标本中MVD较高,这种现象多见于有淋巴结转移的乳腺癌组织中.结论:p53基因可能通过调控VEGF的表达影响瘤内MVD,促使乳腺癌发生转移;而nm23基因可能不是通过调控VEGF的表达,而是通过其他途径影响乳腺癌转移.     

骨肉瘤p53蛋白过度表达与血管生成及预后的关系

目的　研究骨肉瘤p53蛋白过度表达与血管内皮生长因子(VEGF)表达、肿瘤内微血管密度(MVD)的关系,以及它们对骨肉瘤预后的影响。　方法　应用免疫组织化学和形态计量的方法检测80例骨肉瘤p53蛋白和VEGF表达以及MVD计数。　结果　p53蛋白过度表达与VEGF和MVD密切相关,而且三者均为影响骨肉瘤预后的重要因素,依相对危险度大小依次为VEGF>p53>MVD。　结论　p53基因对VEGF和MVD有调节作用,p53蛋白过度表达是肿瘤重要的血管生成表型之一。p53蛋白、VEGF和MVD可能为判估骨肉瘤预后有价值的生物学指标     

肝细胞癌p53和VEGF的表达及其与肿瘤血管形成的关系

目的 :研究p5 3和血管内皮生长因子 (vascularendothelialgrowthfactor ,VEGF)的表达和肿瘤微血管密度 (microvesseldensity ,MVD)测定在人肝细胞癌 (HCC)中的意义。方法 :采用免疫组织化学方法 ,检测 5 0例HCC患者手术切除标本p5 3和VEGF的表达 ,并用抗CD3 4 抗体标记癌组织血管内皮细胞 ,计算MVD。结果 :p5 3、VEGF总阳性表达率分别为 5 4 0 % (2 7 5 0 )和 76 0 % (38 5 0 ) ,p5 3、VEGF的表达和MVD均与HCC组织病理分级呈正相关 ,P <0 0 5。p5 3和VEGF的阳性表达符合率为 74 % (37 5 0 ) ,两者的表达呈相关性 ,P <0 0 5。p5 3阳性和VEGF阳性的癌组织MVD分别为 178± 6 2和 175±5 9 ,而相应的阴性组分别为 12 5± 5 1和 131± 6 1,两者差异有显著意义 ,P <0 0 5。p5 3、VEGF表达均为阳性者 ,MVD为 176± 6 3;p5 3、VEGF的表达均为阴性者 ,MVD为 12 3± 5 2 ;两者差异有显著意义 ,P <0 0 5。结论 :1)p5 3、VEGF的表达以及MVD的测定可作为判断HCC恶性潜能的重要生物学指标 ;2 )p5 3、VEGF的表达对肿瘤血管形成可能起重要作用 ,联合检测p5 3、VEGF的表达对了解肿瘤血管形成的机制有一定意义     

p53和VEGF在食管鳞癌中的表达及其临床意义

背景与目的:实验研究证明p53和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)协同表达在肿瘤血管生成中有重要作用。本研究的目的是探讨p53如何参与血管生成,以及p53和血管内皮生长因子的表达与食管鳞癌(esophagealsquamouscellcarcinoma,ESCC)临床病理参数和预后的关系。方法:采用免疫组织化学方法,检测76例食管鳞癌患者手术切除标本p53和VEGF的表达,并用FⅧ因子抗体标记癌组织血管内皮细胞,计数肿瘤内微血管密度(microvesseldensity,MVD)。结果:p53和VEGF的阳性表达率分别为60.5%和56.6%,两者共同表达率为42.1%。p53和VEGF阳性表达率与食管鳞癌的远处转移和血管浸润具有显著相关性(P<0.05;P<0.01)。远处转移和血管浸润最常发生于突变型p53和VEGF均阳性表达的患者。p53(+)或VEGF(+)组MVD(31.7±11.5;33.8±11.7)均显著高于p53(-)或VEGF(-)组(22.4±10.6;21.2±9.3,P<0.05),p53和VEGF均阳性表达时MVD最大(35.2±11.9,P<0.05)。结论:突变型p53表达与食管鳞癌的血管生成和远处转移密切相关;p53和VEGF的表达可作为评估食管鳞癌恶性程度的重要生物学指标,联合检测p53和VEGF表达具有重要的临床应用价值。     

p53蛋白表达和肿瘤微血管生成与肝癌发展及预后的关系

目的探讨p53蛋白表达和肿瘤微血管生成与肝细胞癌(HCC)发展及预后的关系.方法采用免疫组化方法检测50例肝细胞癌组织中p53蛋白的表达,并用抗CD34抗体标记癌组织血管内皮细胞,计算肿瘤微血管密度(microvessl density,MVD).分析p53蛋白和MVD与HCC临床病理学特征之间的关系.结果 p53阳性表达为癌细胞核棕黄色着色,CD34染色定位在血管内皮细胞上,HCC的p53表达及MVD与肿瘤大小、病灶数目、病理分级、门静脉癌栓形成、包膜是否完整显著相关(P＜0.05).p53蛋白表达阳性者MVD值显著高于阴性者(P＜0.05);p53蛋白表达阳性或MVD≥148的肝癌患者术后生存时间比p53蛋白表达阴性或MVD＜148者短(P＜0.05).结论 p53与肿瘤血管生成密切相关,p53蛋白及MVD可作为肝癌预后判断的一个重要指标.     

Survivin与VEGF在结直肠肿瘤血管形成中的作用

目的 探讨Survivin、血管内皮生长因子(VEGF)在结直肠肿瘤血管形成中的作用.方法 对11例增生性息肉、23例低度异型增生腺瘤、20例高度异型增牛腺瘤、29例腺瘤恶变组织和65例腺癌组织使用Survivin多克隆抗体、VEGF和CD34单克隆抗体、标准化的链霉菌抗生物素蛋白-过氧化物酶技术(SP法)对存档组织块切片进行免疫组化染色,并用MIRS-2000图像分析系统分析其阳性率及表达程度,并行微血管密度(MVD)计数.结果 Survivin表达与VEGF表达及MVD密切相关,且呈明显正相关(r均为0.711,P<0.01).MVD与VEGF表达呈明显正相关(r=0.711,P<0.01).Survivin/VEGF双阳性组较阴性/阳性组及双阴性组MVD值显著增高(P均<0.01),同时对于survivin/VEGF阳性/阴性组,其MVD值与双阳性组筹异无统计学意义(P0.05).结论 Survivin与VEGF表达密切相关,二者协同作用促进结直肠肿瘤血管生成;VEGF可能是结直肠癌中Survivin冉表达的原因之一.     

食管癌组织中p53蛋白表达的临床意义

目的 :探讨p53蛋白表达在食管癌中的临床意义。方法 :用鼠抗人p53单克隆抗体 ,以SP免疫组化法检测p53蛋白。结果 :p53蛋白阳性表达率为 56 3% ,其表达与肿瘤大小、TNM分期、有无淋巴结转移无关 (P >0 0 5) ,与肿瘤分化程度有关 (P <0 0 1)。p53蛋白阳性组与阴性组比较 ,其术后生存率有显著差异 (P <0 0 1)。结论 :食管癌组织中p53蛋白表达与肿瘤大小、TNM分期及有无淋巴结转移无关 ,与肿瘤分化程度密切相关 ,并可用于判断预后     

卵巢上皮癌组织微血管密度及血管形成相关分子的检测及预后价值

目的 探讨卵巢上皮癌组织微血管密度(MVD)、血管内皮生长因子(VEGF)、血小板反应素1(TSP1)和p53蛋白表达与患者预后的关系.方法 采用免疫组化法检测57例原发性卵巢上皮癌组织中VEGF、TSP1和p53蛋白的表达情况,用CD34免疫染色后计数MVD.对VEGF、TSP1、p53蛋白和MVD与患者复发及生存时间的关系进行回顾性分析.结果卵巢上皮癌组织中VEGF、TSP1和p53蛋白表达阳性率分别为70.2%(40/57)、47.4%(27/57)和61.4%(35/57),MVD为30.3±8.5,MVD、VEGF和TSP1与复发相关(P值分别为0.030、0.025和0.026).高MVD、VEGF和p53蛋白阳性患者的中位生存时间短于低MVD、VEGF和p53蛋白阴性者(P值分别为0.0187,0.010和0.005),MVD、VEGF和p53蛋白是影响预后的危险因素.TSP1是影响患者预后的保护因素,其阳性患者的中位生存时间长于阴性患者(P=0.042).多因素分析表明,MVD和p53蛋白是影响卵巢上皮癌预后的独立因素(P值分别为0.018和0.009).结论 VEGF、TSP1和p53蛋白可能参与了卵巢上皮癌的血管形成,MVD和p53是影响卵巢上皮癌预后的独立因素.     

原发性肺癌与食管癌组织中端粒酶活性表达的临床研究

目的 :探讨端粒酶作为一种新的生物学标志物用于常见胸部恶性肿瘤诊断和预后评价等方面的临床应用价值。方法 :采用端粒重复序列扩增法对原发性肺癌、食管癌手术切除组织及相应的癌旁组织进行端粒酶活性分析 ,并以相应的良性病变作为对照。结果 :3 2例肺癌组织中端粒酶阳性率为 84 4%( 2 7/3 2 ) ,癌旁组织为 9 4% ( 3 /3 2 ) ,良性组织中未检出端粒酶阳性。端粒酶活性随肺癌临床分期有升高趋势 ,伴淋巴结转移标本组阳性率 94 7% ( 18/19)明显高于非淋巴结转移组69 2 % ( 9/13 ) ,P <0 0 5 ;但与肿瘤病理组织学类型、分化程度等差异无统计学意义 ,P >0 0 5。 3 7例食管癌端粒酶阳性率为 86 5 % ( 3 2 /3 7) ,癌旁组织为 18 9% ( 7/3 7) ,正常食管组织未检出端粒酶阳性。当癌侵及肌层及外侵后 ,其阳性表达率 10 0 % ( 2 3 /2 3 )高于局限于黏膜及黏膜下层者 71 4% ( 10 /14 ) ,P <0 0 1。伴淋巴结转移标本阳性率 10 0 % ( 2 1/2 1)高于非淋巴结转移者 75 % ( 12 /16) ,P <0 0 5。结论 :端粒酶有可能成为肺癌、食管癌早期诊断和判断预后的重要生物标志物和治疗新靶点。     

乳腺导管原位癌伴微浸润与浸润癌患者的临床特征对比分析

目的:分析乳腺导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCIS-MI）与乳腺浸润性导管癌（invasive ductal carcinoma,IDC）患者的临床特征、治疗方式等。方法:回顾性分析55例乳腺导管原位癌伴微浸润及508例乳腺浸润性导管癌患者的临床资料,包括两组患者的年龄、月经情况、雌激素受体（estrogen receptor,ER）、孕激素受体（progestrone receptor,PR）、人表皮生长因子受体（human epidermal growth factor,HER-2）、肿瘤细胞增殖活性标志物（Ki67）的表达情况、分子分型、治疗方式及预后。结果:DCIS-MI组和IDC组患者在年龄上的差异不具有统计学意义（P＞0.05）,DCIS-MI组在已绝经及淋巴结转移阳性比例均低于IDC组（P＜0.05）;DCIS-MI组Ki67阳性表达率显著低于IDC组（P＜0.05）,ER、PR及HER-2阳性表达率与IDC组比较差异无统计学意义（P＞0.05）。DCIS-MI组Luminal A型比例高于IDC组,而Luminal B(HER-2-)型比例低于IDC组,且差异均具有统计学意义（P＜0.05）。其余分子分型差异不具有统计学意义。DCIS-MI组患者单纯乳房切除术比例（10.9%）显著高于IDC组（0.8%）（P＜0.05）。DCIS-MI患者主要采用的手术方式为乳腺癌改良根治术和全乳切除+腋窝淋巴结清扫,其比例分别为60.0%、16.4%,与IDC组患者采用相同手术方式的比例（67.3%、19.9%）无显著差异。DCIS-MI组化疗比例、放疗比例均低于IDC组（P＜0.05）,而两组患者在内分泌治疗、靶向治疗及中药治疗方面差异不具有统计学意义（P＞0.05）。DCIS-MI组和IDC组患者的5年无病生存（disease-free survival,DFS）率分别为97.0%和81.0%,差异具有统计学意义（Log-rank,χ2=4.962,P=0.026）。结论:与IDC患者相比,DCIS-MI组患者绝经前状态比例高、淋巴结转移阳性率及Ki67阳性率更低,Luminal A型比例更高而Luminal B(HER-2-)型比例更低;DCIS-MI组患者行单纯乳房切除术比例更高,放疗及化疗比例更低,其预后更好。     

Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma

Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over‐expressed Ki‐67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over‐expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki‐67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC.     

EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma

Background:

Approximately 10% of gastric carcinomas are associated with Epstein–Barr virus (EBV). The Inuit in Greenland have a high incidence of EBV-associated nasopharyngeal carcinoma.

Methods:

We conducted a population-based case–control study comparing gastric carcinomas in Greenland and in Denmark.

Results:

The prevalence rate of EBV-associated gastric carcinomas was 8.5% in both populations.

Conclusion:

The findings of this study argue against a general susceptibility to EBV-associated carcinomas among the Inuit.     

Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast.

The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.     

Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS: Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS: A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS: LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma.     

Estrogen receptor expression in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma

Estrogen receptor (ER) expression in salivary gland carcinomas is controversial, and most published studies considered no more than 10 cases. We analyzed ER expression by immunohistochemistry in 136 mucoepidermoid carcinomas and 72 adenoid cystic carcinomas. All cases were negative. These results do not support a role for estrogens in salivary gland mucoepidermoid carcinoma and adenoid cystic carcinoma.