子宫内膜癌ras癌基因产物p21和DNA倍体的研究

为了观察ｒａｓ癌基因产物ｒａｓｐ２１在子宫内膜癌及癌前病变组织中的表达，及ｒａｓｐ２１与ＤＮＡ倍体的关系，应用流式细胞术和细胞免疫荧光技术检测了３２例子宫内膜癌、２６例癌前病变和１０例正常内膜组织中的ｒａｓｐ２１的表达情况。结果为正常内膜组织中ｒａｓｐ２１表达阴性，子宫内膜癌ｒａｓｐ２１的表达高于癌前病变。ｒａｓｐ２１表达的荧光指数随子宫内膜癌组织学分级的升高而增加，但与临床分期、肌层浸润和淋巴结转移无关。ＤＮＡ倍体与ｒａｓｐ２１的表达量有关。表明ｒａｓｐ２１在子宫内膜癌和癌前病变有较高的表达，这可能与子宫内膜癌的发生有关。检测ｐ２１蛋白和ＤＮＡ倍体有助于判断肿瘤的恶性程度和预后。     

子宫内膜癌的诊断治疗进展

子宫内膜癌约占女性生殖道恶性肿瘤的 2 0 %～3 0 % ,其发病率呈逐渐上升趋势 ,有关文献报道子宫内膜癌与子宫颈癌发病率的比率由 60年代的 1∶10改变为现今的 1∶1。子宫内膜癌发病率与年龄、绝经有密切关系 ,其高危因素有 :长期高雌激素 (内源性和外源性 )对子宫内膜的影响、不孕、功血、初潮早与绝经延迟、肥胖、糖尿病、高血压、多囊卵巢综合征及三苯氧胺的应用。1　子宫内膜癌与有关癌基因及抑癌基因的关系目前发现 ,与子宫内膜癌发生、发展有关的癌基因主要有ｒａｓ、ＨＥＲ 2 /ｎｅｕ、ｆｍｓ ,抑癌基因主要有ｐ53。ｒａｓ、ＨＥＲ 2…     

子宫内膜癌p21和p53蛋白表达的研究

目的探讨ｒａｓ癌基因编码的ｐ２１蛋白和ｐ５３抑癌基因蛋白在子宫内膜癌和子宫内膜腺瘤样增生组织的表达情况及其对肿瘤影响。方法应用细胞免疫荧光技术检测了３２例子宫内膜癌和８例子宫内膜腺瘤样增生及１０例正常宫内膜组织的ｒａｓｐ２１及ｐ５３蛋白。结果ｐ２１蛋白在子宫内膜癌的表达高于腺瘤样增生组织，ｐ５３蛋白仅在子宫内膜癌中有表达，ｐ２１和ｐ５３蛋白在正常宫内膜组织无表达。ｐ２１和ｐ５３蛋白的表达量与子宫内膜癌的组织学分级有关，ｐ５３蛋白表达与淋巴结转移有关。结论ｐ２１与ｐ５３蛋白的表达与子宫内膜癌的生物学行为有关，临床可根据ｐ２１和ｐ５３蛋白的表达情况判断肿瘤的恶性程度和预后     

PTEN和CyclinA蛋白在子宫内膜癌组织中的表达及临床意义

目的：探讨PTEN和CyclinA在子宫内膜癌中的表达及其在癌发生发展中的作用。方法：采用免疫组化SP法检测PTEN和CyclinA蛋白在30例正常子宫内膜、30例子宫内膜增生、20例子宫内膜不典型性增生、55例子宫内膜癌组织中的表达。结果：不典型增生组和子宫内膜癌组中PTEN阳性表达率分别为55．00％（11／20）、45．45％（25／55），与全部为阳性表达的正常内膜及阳性表达率为90．00％（27／30）的子宫内膜增生组比较，不典型增生组和癌组中PTEN阳性表达均显著低于正常子宫内膜和子宫内膜增生组（P〈0．05）。CyclinA在不典型增生组和癌组中阳性表达率分别为45．00％（9／20）、67．27％（37／55），显著高于全部阴性表达的正常子宫内膜组和子宫内膜增生组（10．00％，3／30）（P〈0．05）。两者在不典型增生和子宫内膜癌组中的表达均呈显著性负相关（r=-0．5330，r=-0．5556；P〈0．001）。癌组中PTEN阳性表达的缺失与组织学分级有关（P〈0．05），但与肿瘤的浸润转移、临床分期和复发无关（P〉0．05）；CyclinA的阳性表达率与组织学分级、肿瘤的浸润转移和临床分期、复发有关。结论：PTEN表达缺失和CyclinA的过度表达涉及子宫内膜癌的发生、发展过程，二者联合检测可作为子宫内膜癌早期诊断、判断肿瘤生物学行为的免疫学指标。     

影响子宫内膜腺癌预后相关因素分析

目的应用多指标、综合分析方法评价影响子宫内膜癌预后因素的临床意义。方法采用肿瘤实验室检测和临床治疗学随访相结合方法观测临床分期等７项指标与预后的关系。结果临床分期、病理分级、肌层浸润、雌激素受体（ＥＲ）、孕激素受体（ＰＲ）和ＤＮＡ倍体与子宫内膜癌预后和五年生存率间高度相关，而血管内癌栓与预后无相关性。结论正确的临床分期、病理分级和肌层浸润是影响内膜癌预后的重要指标，ＥＲ、ＰＲ、ＤＮＡ与治疗后预后有相关性。     

bcl-2、p53和PCNA子宫内膜增生与内膜癌的表达

[目的]探讨bcl-2、p53蛋白和增殖细胞核抗原（PCNA）表达与子宫内膜增生性病变和内膜癌的关系。[方法]应用免疫组织化学ABC法对子宫内膜场50例,不典型子宫内股增生、复杂型子宫内膜增生和单纯型内膜增生各15例,进行bcl－2、p53蛋白和PCNA的检测。[结果]bcl－2、p53在内膜癌、不典型子宫内膜增生、复杂型子宫内膜增生的表达分别为64．0％和52.0％,40．0％和20．0％,13．3％和0,单纯型子宫内膜增生表达均为阴性。内膜癌、内膜不典型增生及复杂型单纯型增生三者之间差异有显著性（P＜0．01）。PCNA在子宫内膜癌、不典型子宫内膜增生表达为100．0%和73.3%,显著高于复杂型及单纯型子宫内膜增生（26．7%和20.0％,P＜0．05）。本实验发现p53和PCNA与内膜癌分化程度,转移扩散有关（P＜0．05）,与临床分期,肌层浸润之间无显著相关性（P＞0．05）。bcol－2与内膜癌分化程度有关,与转移、扩散、分期及肌层浸润之间无显著相关性。[结论]p53和PCNA联合检测可以作为子宫内膜癌预后判断的良好指标。bcl－2与PCNA在不典型内膜增生内有较高表达,是癌变危险因素,联合检测有较高价值。     

bcl—2,p53和PCNA子宫内膜增生与内膜癌的表达

（目的）探讨ｂｃｌ－２ｐ５３蛋白和增殖细胞核抗原（ＰＣＮＡ）表达与子宫内膜增生性病变和内膜癌的关系。（方法）应用免疫组织化学ＡＢＣ法对于子宫内膜癌５０例,不典型子宫内膜增生,复杂型子宫内膜增生和单纯型内膜增生各１５例,进行ｂｃｌ２,ｐ５３蛋白和ＰＣＮＡ的检测,（结果）ｂｃｌ－２,ｐ５３在内膜癌,不典型子宫内膜增生,复杂型子宫内膜增生的表达分别为６４．０％和５２．０％,４０．０％和２０．０％,１３．     

PTEN 在不同类型子宫内膜中的表达

目的：检测PTEN在不同类型子宫内膜组织中的表达，探讨其在内膜癌发生中的作用。方法：应用SP法检测88例子宫内膜组织中PTEN蛋白的表达，结合临床病理资料进行分析。结果：PTEN在正常内膜、单纯增生、复合增生、不典型增生及内膜癌中的表达率分别为：85％、77．7％、66．6％、90％和44．7％。按正常内膜到内膜癌的顺序与PTEN的表达强度进行相关分析，两者呈负相关（r=-0．446，P=0．000）；内膜癌组，PTEN表达率在Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别是48．1％、75％、16．6％、0％，在G1、G2、G3分别为63．6％、35．2％、40％，在肌层无侵袭、侵袭〈1／2和肌层〉1／2肌层分别是42．8％、41．6％、57．1％，PTEN表达与三者均无关；内膜癌中PTEN的表达与血CA125水平呈负相关（r=-0．327，P=0．04）。结论：PTEN蛋白的低表达与内膜癌发生发展相关，PTEN表达与内膜癌临床分期、病理分级及肌层浸润可能无关。     

p14^ARF和p53在子宫内膜癌组织中的表达及其临床意义

目的：研究子宫内膜癌组织中p14^ARE。和p53的表达及意义。方法：采用免疫组化LSAB法，检测118例子宫内膜癌及30例正常宫内膜组织中p14^ARE及p53的表达。结果：p14^ARE。阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为25．4％（30／118）、38．1％（45/118）、14．4％（17／118）和22．0％（26／118），与正常内膜0（0／30）、56．7％（17／30）、33．3％（10／30）和10．0％（3／30）相比差异有统计学意义，P〈0．001，子宫内膜癌中p14^ARE。表达缺失的比例高于正常宫内膜；p14^ARE表达水平与手术病理分期、宫颈间质受累和淋巴结转移相关；与病理分级、组织学类型和肌层侵犯深度无关；不同p14^ARE表达水平患者生存率差异无统计学意义，P=0．5781。p53阴性、弱阳性、中度阳性和强阳性表达率在子宫内膜癌中分别为13．6％（16／118）、40．1％（48／118）、28．0％（33／118）和17．8％（21／118）；与正常内膜相比分别为36．7％（11／30）、36．7％（11／30）、16．2％（5／30）和10．0％（3／30）差异有统计学意义，P=0．01．子宫内膜癌中p53阳性表达的比例高于正常宫内膜；p53表达与肿瘤分期、盆腔淋巴结转移和肌层侵犯深度相关，与病理分级、组织学类型和宫颈间质受累无关；不同p53表达水平患者生存率差异无统计学意义，P=0．4166；在子宫内膜癌组织中p14^ARE。与p53表达呈负相关，r=-0．243，P=0．008。结论：p14^ARE和p53异常表达与子宫内膜癌发生密切相关，但对其预后的影响有待进一步的研究。     

CA—125与子宫内膜抗体测定在子宫内膜异位症诊断中的价值

测定２８例子宫内膜异位症患者及１４例正常健康妇女血清ＣＡ－１２５和子宫膜抗体（ＥＭＡｂ）水平。结果，血清ＣＡ－１２５浓度与子宫内膜异位症临床分期呈正相关，Ⅲ、Ⅳ期子宫内膜异位症患者血清ＣＡ－１２５明显高于对照组；子宫内膜异位症患者血清ＥＭＡｂ明显高于对照组。两者用于子宫内膜异位症诊断的敏感性分别为７１．４３％和８２．１４％，特异性分别为５７．２１％和５７．１４％。     

Expression of vascular endothelial growth factor and HER2/neu in stage II colon cancer and correlation with survival

Monoclonal antibody-directed therapy has been used as an effective treatment for some cancers that overexpress HER2/neu and vascular endothelial growth factor (VEGF). Overexpression of the HER2/neu oncogene and VEGF has been reported to occur in adenocarcinomas of the colon. Assessing whether HER2/neu and VEGF overexpression could serve as prognostic indicators for stage II colon cancer may provide insight into optimal treatment following surgery. Demographic and tumor characteristics from 109 patients diagnosed with stage II colon cancer between 1991 and 1996 were assessed for HER2/neu and VEGF expression using immunohistochemical staining techniques. Of the 109 cases, 107 (98%) were histologically classified as adenocarcinomas, 105 (96%) were grades 2/3, and 105 (96%) were stage T3. Only 12 cases (11%) exhibited HER2/neu overexpression and 72 cases (66%) exhibited VEGF expression. There was no significant difference in overall survival or in time to recurrence between the groups with and without HER2/neu overexpression. There was a trend toward decreased overall survival with VEGF expression (P = 0.07), but no difference in time to recurrence (P = 0.63). There were 18 patients who received adjuvant chemotherapy, but removal of these patients from the analysis did not change the results. There was no association between HER2/neu and VEGF expression and patient demographics or tumor characteristics, with the exception of VEGF expression and mucinous histology (P < 0.01). Our results do not support an association between HER2/neu or VEGF expression and overall survival or time to recurrence in stage II colon cancer. With further investigation, a significant correlation may be found between VEGF expression and prognosis, and thus direct therapy with a monoclonal antibody.     

HER 2/neu expression and gene amplification in colon cancer

HER 2/neu is an important oncogene in breast cancer, but the prevalence and significance of HER 2/neu gene amplification in colon cancer have been poorly documented. We have evaluated HER 2/neu gene amplification and protein overexpression in a series of colon cancers to assess the frequency, concordance and clinical significance of these events. HER 2/neu gene copy number was measured in 154 primary colon tumors, 15 liver metastases and matched normal tissues using a quantitative PCR/ligase detection reaction (LDR) technique developed and validated in our laboratory. HER 2/neu copy number was confirmed by fluorescent in situ hybridization (FISH) in all tumors found to have gene amplification. In an independent and blinded fashion, HER 2/neu expression was assessed in paraffin sections from 139 of the tumor specimens using the HercepTest kit. HER 2/neu gene amplification was observed in 4 (2.4%) of the 169 tumor specimens and in none of the normal tissues. There was no apparent association with stage of disease, tumor grade or patient survival. Among 139 cases evaluated by immunohistochemistry (IHC), HER 2/neu overexpression was seen in 5 cases (3.6%). There was extremely high concordance (kappa = 0.852) between gene amplification and protein overexpression. The low prevalence of HER 2/neu gene amplification and protein overexpression suggests that this oncogene plays an infrequent role in the development and progression of colon cancer. These data indicate that the primary mechanism of dysregulated HER 2/neu expression in colon cancer, as in breast cancer, is gene amplification.     

子宫内膜癌PCNA表达的研究

本文应用免疫组化技术，对103例子宫内膜癌组织中增殖细胞核抗原（ProliferatingCellNuctearAntigen，PCNA）的表达进行了研究。结果表明：PCNA的高度表达与肿瘤的组织分级有关，分级越高，PCNA的高度表达率越高。PCNA的表达与肿瘤的肌层浸润、脉管浸润、分期无关。DNA异倍体组织中PCNA的高度表达率高于二倍体。PCNA高度表达者的生存率显著低于低度表达者，两者的5年生存率分别为58.2％及82．3％。本文结果提示，PCNA可作为反映子宫内膜癌增殖活性及判断其预后的一个重要指标。     

HER2和BRCA1在子宫内膜癌中的表达及其与预后的关系

目的探讨人表皮生长因子受体-2(human epidermal growth factor receptor 2,HER2)和乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)在子宫内膜癌中的表达及其与预后的关系。方法采用免疫组织化学方法检测79例子宫内膜癌、40例非典型增生子宫内膜、30例正常子宫内膜组织中HER2与BRCA1的表达,并结合随访资料分析这2个指标与患者生存时间的关系。结果在正常子宫内膜、非典型增生子宫内膜、子宫内膜癌中HER2阳性表达率分别为6.7%、17.5%、67.1%(P=0.000),BRCA1阳性表达率分别为93.3%、62.5%、31.7%(P=0.000)。子宫内膜癌中,HER2阳性表达与组织分化、手术病理分期、肌层浸润及淋巴结转移有关(均P<0.05),BRCA1阳性表达与组织分化、手术病理分期及淋巴结转移有关(均P<0.05);HER2阳性表达患者的5年生存率低于HER2阴性表达患者(69.8%vs 92.3%,P<0.05),BRCA1阳性表达患者与阴性表达患者的5年生存率差异无统计学意义(84.6%vs 72.2%,P>0.05);BRCA1与HER2蛋白在子宫内膜癌中表达无相关性(r=-0.103,P>0.05)。结论 BRCA1的表达缺失可能与子宫内膜癌的发生、发展有关,HER2蛋白的高表达与子宫内膜癌侵袭性及不良预后有关。     

HER2/neu antisense targeting of human breast carcinoma

Overexpression of the HER2/neu oncogene is observed in approximately 30% of human breast carcinoma specimens. HER2/neu overexpression is a negative prognostic factor in breast cancer patients. Cancer cells that overexpress HER2/neu may also be less sensitive to chemotherapy. In order to further define mechanisms by which HER2/neu overexpression drives neoplastic cell growth and chemoresistance, antisense oligonucleotides (ODNs) have been utilized to selectively down-regulate HER2/neu expression in human breast cancer cells. Such antisense ODNs suppress HER2/neu mRNA and protein levels in a dose-dependent, sequence-specific manner. Down-regulation of HER2/neu expression in HER2/neu overexpressing breast cancer cells inhibits cell cycle progression in G0/G1 and results in apoptotic cell death. In tissue culture studies, combined treatment of HER2/ neu overexpressing breast cancer cells with HER2/neu antisense ODNs and conventional chemotherapeutic agents results in synergistic inhibition of cancer cell growth and activation of apoptotic cell death mechanisms. These studies have been extended to demonstrate synergistic antitumor effects following systemic treatment with antisense ODNs plus doxorubicin in nude mice bearing human breast carcinoma xenografts. Collectively these findings demonstrate that HER2/neu overexpression stimulates anti-apoptotic cell survival mechanisms and suggest that HER2/neu antisense ODNs may be of use in cancer therapeutics.     

p53、p21ras、nm23-H1基因在子宫内膜癌中表达与临床病理关系研究

 目的　研究p53、p21ras、nm23-H1基因在子宫内膜癌中的表达与临床病理学关系。方法　应用免疫组织化学方法(SABC法)研究18例正常增生期子宫内膜、12例子宫内膜非典型性增生过长、78例子宫内膜癌的p53、p21ras、nm23-H1基因的表达情况。结果　12例增生期子宫内膜中p53和p21ras基因表达阴性,3例子宫内膜非典型性增生过长中p53阳性;p53、p21ras、nm23基因在子宫内膜癌中表达率分别为57.69%,55.12%,71.79%;p53的表达在不同的临床分期,病理学分级,有无淋巴结转移和是否绝经之间差异有显著性意义(P<0.01);p21ras基因表达与病理学分级及有无淋巴结转移有关(P<0.05),但与临床分期无关;nm23-H1的表达与病理学分级,临床分期,有无淋巴结转移有关。结论　p53、p21ras、nm23基因在子宫内膜癌中均高表达,p53的表达和肿瘤发生,发展有关,p21ras基因表达与肿瘤的进展有关,nm23的表达与淋巴结转移呈负相关。     

子宫内膜癌和子宫颈癌p21与DNA倍体的研究

目的研究ｒａｓｐ２１致癌基因和ＤＮＡ倍体与子宫颈癌及子宫内膜癌的关系。方法应用细胞免疫荧光技术和流式细胞术对４０例宫颈癌、２０例慢性宫颈炎、３２例子宫内膜癌和１３例癌前病变进行了ｒａｓｐ２１致癌基因的表达量及ＤＮＡ倍体的测定。结果子宫颈癌和子宫内膜癌ｒａｓｐ２１的表达量高于慢性宫颈炎和子宫内膜癌前病变,并与二者的组织学分级有关。ＤＮＡ倍体与ｒａｓｐ２１的表达量有关。结论ｒａｓｐ２１的表达与子宫颈癌和子宫内膜癌的发生有关。检测ｐ２１蛋白和ＤＮＡ倍体有助于判断这两种肿瘤的恶性程度和预后,并应积极治疗慢性宫颈炎     

p53、p21ras、nm23-H1基因在子宫内膜癌中表达与临床病理关系研究

目的　研究p53、p2 1ras、nm2 3 H1基因在子宫内膜癌中的表达与临床病理学关系。方法　应用免疫组织化学方法 (SABC法 )研究 18例正常增生期子宫内膜、12例子宫内膜非典型性增生过长、78例子宫内膜癌的p53、p2 1ras、nm2 3 H1基因的表达情况。结果　 12例增生期子宫内膜中p53和p2 1ras基因表达阴性 ,3例子宫内膜非典型性增生过长中p53阳性 ;p53、p2 1ras、nm2 3基因在子宫内膜癌中表达率分别为 57 69% ,55 12 % ,71 79% ;p53的表达在不同的临床分期 ,病理学分级 ,有无淋巴结转移和是否绝经之间差异有显著性意义 (P <0 0 1) ;p2 1ras基因表达与病理学分级及有无淋巴结转移有关 (P <0 0 5) ,但与临床分期无关 ;nm2 3 H1的表达与病理学分级 ,临床分期 ,有无淋巴结转移有关。结论　p53、p2 1ras、nm2 3基因在子宫内膜癌中均高表达 ,p53的表达和肿瘤发生 ,发展有关 ,p2 1ras基因表达与肿瘤的进展有关 ,nm2 3的表达与淋巴结转移呈负相关。     

子宫内膜癌C—erbB2基因蛋白表达与预后的关系

目的:为探讨C-erbB2基因与子宫内膜癌的关系。方法:作者应用免疫组化检测了64例子宫内膜癌、16例正常子宫内膜、32例子宫内膜增殖症、5例子宫内膜息肉组织中C-erbB2基因蛋白的表达情况。结果:C-erbB2阳性表达率在癌、内膜增殖症、正常内膜分别为60.9％、21.9％、18.8％,息肉均无阳性表达,癌与增殖症、正常内膜比较差异有显著性(P<0.05)。C-erbB2阳性表达与临床分期、组织学分级有相关性,而与病理类型、肌层浸润无关。阳性表达的患者3年、5年生存率明显低于阴性患者(P<0.01)。结论:C-erbB2与子宫内膜癌的发生、发展密切相关,可以作为评估其恶性生物学行为和预后的指标。     

Effect of HER2/neu expression on survival in non-small-cell lung cancer

Major prognostic factors for early-stage non-small-cell lung cancer (NSCLC) are tumor size and nodal status. It has been suggested that HER2/neu overexpression may be related to poor prognosis in NSCLC. We evaluated the significance of HER2/neu overexpression on survival in patients with NSCLC. Data were collected on 239 patients treated surgically for stage I/II NSCLC between 1987 and 1996. None of the patients received adjuvant chemotherapy or radiation. Formalin-fixed, paraffin-embedded tumor tissue samples were stained with p185/HER2 receptor antibody. Results were reported as positive (2+, 3+) or negative (0, 1+) (Group A). A separate analysis considered only 3+ as positive (Group B). HER2/neu overexpression was seen in 18% in Group A (43 of 239) and 6% in Group B (15 of 239). HER2/neu overexpression was highest in bronchoalveolar cell carcinoma and adenocarcinoma. More stage I tumors were positive than stage II in both groups, but this was significant only in Group A (21% vs. 7%, P = 0.02). No difference was seen with age, gender, or grade for either group. In Group A, the relapse rate was 55% for HER2/neu-overexpressing tumors and 31% for HER2/neu-negative tumors (P = 0.003). Median time to relapse in patients with HER2/neu-positive tumors was 2.9 years; it was not reached in patients with HER2/neu-negative tumors. Median survival of patients with HER2/neu-positive tumors was 3.6 years compared to 5 years in patients with HER2/neu-negative tumors (P = 0.66). In Group B, the relapse rate was 60% for HER2/neu-overexpressing tumors and 33% for negative tumors (P = 0.036). Median time to relapse was 3.4 years in HER2/neu positive and had not been reached in negative tumors. There was no difference in 5-year survival rates for both groups (47% for HER2/neu positive and 50% for negative, P = 0.66).