细胞周期素Dl与p53蛋白在卵巢上皮性肿瘤的表达及意义

目的：探讨细胞周期素D1(CyclinD1)与p53蛋白在卵巢上皮性肿瘤的表达及意义。方法：1990--1995年应用免疫组化法对40例恶性卵巢上皮性肿瘤及20例良性卵巢上皮性肿瘤组织进行CyclinD1与p53蛋白检测。结果：良性卵巢上皮性肿瘤CyclinD1阳性表达为10．0％，而恶性卵巢上皮性肿瘤CyclinD1阳性表达为37．5％。良性卵巢上皮性肿瘤p53阳性表达为15．0％，恶性卵巢上皮肿瘤p53阳性表达为47．5％。CyclinD1在卵巢上皮癌Gl与G2、G3中的阳性表达统计学差异有显著性(P＜0．05)，p53蛋白在早期卵巢上皮癌与晚期卵巢上皮癌组织中的阳性表达，统计学差异有显著性(P＜0．05)，p53蛋白的阳性表达在卵巢癌G1与G2、G3比较差异有显著性(P＜0．05)。CyclinD1过表达的细胞同时也有p53的过表达。结论：CyclinD1与p53蛋白在卵巢上皮性肿瘤的共同表达可能是促进卵巢上皮性肿瘤发展的因素。     

卵巢上皮性癌nm23-H1基因蛋白的表达及其意义

目的：探讨卵巢上皮性癌病人nm23-H1基因蛋白表达与临床分期、分化程度及预后的关系及意义。方法：采用单克隆抗体免疫组织化学方法S－P法，对70例卵巢上皮性癌手术标本经10％福尔马林固定，石蜡包埋组织进行nm23-H1基因蛋白表达的测定。结果：I－Ⅱ期卵巢上皮性癌nm23-H1基因蛋白表达阳性率为81．2％。Ⅲ-Ⅳ期阳性率为46．3％，差异具有显著意义（P＜0．05），随着卵巢上皮性癌病理学分级的增高，nm23-H1基因蛋白表达阳性率下降，差异具有极其显著意义（P＜0．01）。Ⅲ-Ⅳ期卵巢上皮性癌nm23-H1基因蛋白表达在生存期大于或等于3年及小于3年间差异具有极其显著的意义（P＜0．01）。结论：测定卵巢上皮性癌组织中nm23-H1基因蛋白表达，对判断预后有积极的作用。     

子宫内膜癌中MTS1／p16基因的表达及临床意义初探

目的：探讨MTS1／p16基因产物在子宫内膜癌中的表达及其临床意义。方法：采用免疫组化方法（SP法）检测p16蛋白在52例子宫内膜癌和26例正常子宫内膜组织中的表达。结果：p16蛋白阳性表达多位于胞浆内,亦可见于胞核内,p16蛋白在正常子宫内膜组阳性表达率为88．5％（23／26）,而子宫内膜癌组织阳性表达率为57．7％（30／52）,其表达在子宫内膜癌不同组织分化,临床分期及有无淋巴转移间阳性率有显著差异（P＜0．05）。子宫内膜癌p16蛋白阴性者组织分化程度低,临床分期晚且多有淋巴结转移。结论：对子宫内膜癌p16蛋白表达的检测有助于分析其细胞分化程度,判断有无淋巴结转移。     

血小板反应素-1在卵巢上皮癌组织的表达及与p53肿瘤抑制蛋白和肿瘤血管形成的关系

目的：检测血小板反应素-1（TSP-1）和p53肿瘤抑制蛋白在卵巢上皮癌的表达，并探讨其表达与肿瘤血管形成及患者预后的关系。方法：用免疫组化法检测57例原发性卵巢上皮癌组织和22例正常卵巢组织中TSP-1和p53蛋白的表达，并用CD34抗体免疫染色后对微血管密度（MVD）计数。结合随诊资料，回顾分析上述指标与卵巢上皮癌临床病理特征及3年存活率之间的关系。结果：卵巢上皮癌组织中TSP-1的阳性表达率低于正常卵巢组织（分别为47．4％和72．7％，P=0．042），且多为弱阳性表达；卵巢上皮癌组织中p53的阳性率为61．4％，正常卵巢组织未检测到p53蛋白。TSP一1表达和p53蛋白阳性与卵巢上皮癌的手，术病理分期、大网膜转移和癌性腹水相关。卵巢上皮癌组织的MVD高于正常卵巢组织（分别30．3土8．5和20．1±8．1，P=0．014）。TSP-1表达与MVD呈负相关（P〈0．001），p53蛋白阳性与MVD呈正相关（P〈0．001）。TSP-1表达与患者的3年存活率呈正相关（P=0．001），p53蛋白阳性与3年存活率呈负相关（P=0．002）。TSP-1阴性而p53蛋白阳性组患者的3年存活率明显低于TSP-1阳性而p53蛋白阴性组（分别为13．6％和78．6％，P〈0．001）。结论：卵巢上皮癌组织TSP-1和p53蛋白的表达与肿瘤血管形成有关，对上述分子的检测有助于临床判断卵巢上皮癌的生物学行为。     

子宫颈癌组织中抑癌基因DNA甲基化的检测

目的 通过分析宫颈上皮内瘤变（CIN）和宫颈癌组织中p16、CDH1、RASSF1A和TIMP3基因DNA甲基化的变化情况,探讨其在宫颈癌发生中的意义。方法 用甲基化特异性聚合酶链反应技术（MSP）对CINI组（40份）、CINⅡ～Ⅲ（40份）、宫颈癌组（40份）病变组织中p16、CDH1、RASSF1A和TIMP3基因DNA甲基化程度进行检测。另取正常宫颈组织20份作为对照组。结果（1）对照组中p16、CDH1、RASSF1A和TIMP3基因的DNA甲基化阳性率均为0。（2）p16和CDH1基因的DNA甲基化阳性率,CIN11～m组（分别为22％、35％）明显高于CINI组（分别为2％、5％,P〈0．05）;RASSF1A和TIMP3基因的DNA甲基化阳性率,CINⅡ～Ⅲ组（分别为12％、15％）虽高于CINI组（均为2％）,但差异无统计学意义（P〉0．05）。（3）宫颈癌组p16（40％）、CDH1（58％）、RASSF1A（20％）和TIMP3（35％）基因的DNA甲基化阳性率虽均高于CINⅡ-Ⅲ组,但差异无统计学意义（P〉0．05）。（4）宫颈癌组p16、CDH1、RASSF1A和TIMP3基因的DNA甲基化阳性率均高于CINI组,差异有统计学意义（P〈0．05）。（5）上述基因的DNA甲基化的总阳性率（即任何一个基因出现甲基化即为阳性）,宫颈癌组（90％）明显高于CINⅡ～Ⅲ组（55％,P〈0．05）,且此两组均明显高于CINI组（8％,P〈0．05）。结论 随着从宫颈不典型增生向浸润癌的进展,p16、CDH1、RASSF1 A和,TIMP3基因的DNA甲基化阳性率明显升高,提示抑癌基因的DNA甲基化在宫颈癌发生、发展中起着一定作用,可能成为判断宫颈癌发生、发展的重要指标。     

卵巢上皮性肿瘤的临床病理特征及其细胞周期素D1和p53蛋白表达的研究

目的研究卵巢上皮性癌（卵巢癌）和交界性上皮性肿瘤的临床病理特征及其细胞周期素D1（cyclin D1）和p53蛋白表达的情况,探讨卵巢癌和交界性上皮性肿瘤在发病机制上的联系。方法分析45例卵巢癌（卵巢癌组）和54例卵巢交界性上皮性肿瘤（交界性肿瘤组）的临床病理资料,采用免疫组化法检测两组组织中cyclin D1、p53蛋白的表达情况,并分析其与临床病理特征的相关性。结果（1）临床病理特征：①年龄：交界性肿瘤组平均年龄为42．5岁（14～82岁）,中位数年龄41岁;卵巢癌组平均年龄为53．5岁（26～80岁）,中位数年龄51岁。②分期：按国际妇产科联盟（FIGO）分期标准,交界性肿瘤组Ⅰ期48例、Ⅱ期3例、Ⅲ期3例;卵巢癌组Ⅰ期6例、Ⅱ期8例、Ⅲ期26例、Ⅳ期5例。③病理类型：交界性肿瘤组以黏液型为主[占56％（30／54）],其次为浆液型[其中普通型11例,微乳头型5例;占30％（16／54）];卵巢癌组以浆液型（其中低度恶性19例,高度恶性3例）为主[占49％（22／45）]。④病理分化程度：卵巢癌组高分化5例,中分化17例,低分化或未分化23例。⑤预后：交界性肿瘤组5年生存率为98％,卵巢癌组为51％,两组比较,差异有统计学意义（P=0．000）。（2）cyclin D1和p53蛋白的表达及其与卵巢癌和交界性肿瘤临床病理特征的相关性：卵巢癌组cyclin D1和p53蛋白的阳性表达率分别为31％（14／45）和56％（25／45）,p53蛋白表达强度与病理分化程度呈正相关（r=0．320,P=0．032）;交界性肿瘤组cyclin D1和p53蛋白的阳性表达率分别为69％（37／54）和6％（3／54）。其中,普通型浆液性交界性肿瘤与高度恶性浆液性癌比较（两者cyclin D1蛋白阳性表达率分别为91％和26％,p53蛋白分别为0和58％）,差异有统计学意义（P〈O．01）;而微乳头型浆液性交界性肿瘤与低度恶性浆液癌比较（两者cyclin D1蛋白阳性表达率分别为3／5和2／3,p53蛋白分别为1／5和1／3）,差异则无统计学意义（P〉0．05）。结论cyclin D1蛋白的过度表达常见于卵巢浆液性交界性肿瘤及低度恶性浆液性癌组织中,而p53蛋白的过度表达更多见于高度恶性浆液性癌组织中。卵巢浆液性交界性肿瘤与高度恶性浆液性癌具有不同的发病机制,而微乳头型浆液性交界性肿瘤与低度恶性浆液性癌的关系可能更为密切。     

抑癌基因PTEN与错配修复基因hMLH1在子宫内膜癌中的表达及意义

目的 探讨抑癌基因PTEN及错配修复基因hMLH1在子宫内膜癌（UEC）中的表达及其与子宫内膜癌的临床病理学参数的关系。方法 于2002—2004年采用免疫组化SP法，检测36例散发性子宫内膜癌、22例子宫内膜不典型增生（AH）、23例正常子宫内膜（NE）组织中PTEN及hMLH1的表达。结果 （1）hMLH1基因在NE、AH和UEC中的表达分别为83％（19／23）、64％（14／22）和11％（4／36），AH及NE的表达与其在UEC中的表达差异有显著性（P〈0.01），而前两者比较差异无显著性（P〉0．05）。（2）hMLH1基因表达UEC的淋巴结转移、肌层浸润、手术分期、病理类型差异无显著性（P〉0.05），与子宫内膜癌病理分化程度有关（P〈0．01）。（3）PTEN基因在NE、AH和UEC中的表达分别为100％（23／23）、73％（16／22）和56％（20／36），在AH、UEC中的表达与其在NE中的表达差异有显著性，而前两者比较差异无显著性（P〉0．05）。（4）PTEN基因表达与子宫内膜癌的分化程度、淋巴结转移、手术分期、病理类型、肌层是否浸润无统计学相关（P〉0．05）：（5）PTEN及hMLH1两种基因蛋白在子宫内膜癌变过程中的表达有相关性（相关系数r=0．28；P〈0．05）：结论（1）hMLH1及PTEN均是子宫内膜的保护性基因，在子宫内膜的癌变过程中表达逐渐减少，可能与早期子宫内膜癌癌变的启动有关，且二者有显著的相关性。（2）免疫组化法测定PTEN的表达有可能成为筛选子宫内膜癌变的早期指标，（3）测定hMLH1的表达有可能成为预测子宫内膜癌预后的指标。     

p16和CDH1基因异常甲基化在宫颈组织中的表达及其意义

目的:分析宫颈癌和宫颈上皮内瘤样病变(cervical intraepithelial neoplasia, CIN)组织中p16和CDH1基因异常甲基化的变化,评价该指标在宫颈癌中的意义。方法:用甲基化特异性聚合酶链反应法(methylation-specific PCR,MSP)检测CINⅠ40例、CINⅡ～Ⅲ40例、宫颈癌40例组织中p16和CDH1基因的异常甲基化。取正常宫颈组织20例作为对照。结果:(1)p16和CDH1甲基化在正常组未见表达;(2)p16、CDH1甲基化阳性率:CINⅡ、Ⅲ组明显高于CINⅠ组,差异有统计学意义(22．4%vs 2．5%,P＜0．05; 35．0%vs 5．0%,P＜0．05),宫颈癌组高于CINⅡ、Ⅲ组,但差异无统计学意义(40．0% vs 22．4%,P＞0．05;57．5% vs 35．0%,P＞0．05);宫颈癌组高于相应CINⅠ组,差异有统计学意义(40．0% vs 2．5%,P＜0．05;57．5% vs 5．0%,P＜0．05);(3)p16和CDH1甲基化总阳性率(任何一个基因出现甲基化即为阳性):CINⅡ、Ⅲ组明显高于CINⅠ组,差异有统计学意义(40．0% vs 5．0%,P＜0．05),宫颈癌组高于CINⅡ、Ⅲ组,差异有统计学意义(70．0% vs 40．0%,P＜0．05)。结论:p16和CDH1基因启动子区异常甲基化与宫颈癌的生物学行为相关,它可能有助于宫颈癌的早期辅助诊断和治疗。     

人宫颈癌bcl-2基因表达与预后的关系

目的 探讨人宫颈中ｂｃｌ－２基因表达的改变与其临床意义。方法 对１４９例宫颈组织采用免疫组化ＡＢＣ法检测ｂｃｌ－２基因蛋白的表达,结合临床资料分析该基因改变的临床意义。结果 宫颈癌中ｂｃｌ－２基因蛋白表达（５５．２９％）显著高于宫颈下沉和炎症组织（１８．７５％）（ｐ〈０．０１）,其中０期（３／３）、Ⅰ期（８４．６２％）、Ⅱ期（７４．５１％）显著高于Ⅲ期（２８．５７％）（ｐ〈０．０１）。ｂｃｌ－２蛋     

功能失调性子宫出血和细胞凋亡,bcl-2及bax基因表达的关系

目的研究功能失调性子宫出血与细胞凋亡及其相关基因表达产物的关系。方法应用TUNEL技术检测30例正常月经周期的增生期子宫内膜，28例简单增生，2例复杂增生子宫内膜标本的凋亡指数（AI）。应用免疫组化方法检测bcl-2及bax基因在子宫内膜的表达。结果简单增生和复杂增生子宫内膜AI比正常增生期AI高（P＜0．05）；bcl-2基因在正常增生期表达比在简单增生和复杂增生表达略高，差异无显著性（P＞0．05）；bax基因在简单增生和复杂增生表达比在正常增生期表达高（P＜0．05）。结论功能失调性子宫出血的发病与细胞凋亡有关，且与bcl-2，bax表达相关。     

子宫颈鳞状细胞癌中细胞凋亡相关基因产物的免疫组织化学研究

目的：研究子宫颈鳞状细胞癌组织中细胞凋亡的相关基因表达及其与临床病理特征和患者预后的关系。方法：用免疫组织化学ＬＳＡＢ方法，分析５１份子宫颈鳞癌石蜡包埋组织中细胞凋亡相关基因ｐ５３、Ｃ－ｍｙｃ、ｂｃｌ－２及ｂａｘ的表达情况。另取石蜡包埋的正常子宫颈组织５份、上皮内瘤样病变（ＣＩＮ）组织８份作为对照。结果：１．ｐ５３、Ｃ－ｍｙｃ、ｂｃｌ－２和ｂａｘ在子宫颈鳞癌中的表达率分别为５２．９４％（２７／５１）、４９．０２％（２５／５１）、４３．１３（２２／５１）及５２．９４（２７／５１），其中ｐ５３、Ｃ－ｍｙｃ表达与正常子宫颈组织及ＣＩＮ比较差异有显著性（Ｐ＜０．０５）。２．子宫颈鳞癌中ｍｔｐ５３表达多见于组织分化程度低、有淋巴结转移及不良预后的患者。Ｃ－ｍｙｃ在有淋巴结转移及预后不良患者中表达显著增高。在分化程度高、无淋巴结转移患者中ｂｃｌ－２高表达。在临床分期晚、分化程度低、有淋巴结转移患者中ｂａｘ高表达。３．ｐ５３与ｂｃｌ－２以及ｂｃｌ－２与ｂａｘ表达间呈负相关；ｐ５３与ｂａｘ以及Ｃ－ｍｙｃ与ｂａｘ表达间呈正相关。结论：细胞凋亡相关基因ｐ５３、Ｃ－ｍｙｃ、ｂｃｌ－２及ｂａｘ在子宫颈鳞癌的发生、发展中起一定作用，?     

Immunohistochemical analysis of survivin expression in primary breast cancers.

BACKGROUND AND PURPOSE: Survivin, an inhibitor of apoptosis, is expressed in fetal tissues but undetectable in normal adult tissues. It is also expressed in most common human cancers. This study evaluated the expression of survivin in breast cancers. METHODS: A monoclonal anti-survivin antibody B1 was generated. Immunohistochemical staining was performed in 226 paraffin sections of primary breast cancers and correlated with the patients' clinicopathological characteristics. RESULTS: Survivin was expressed in the cytoplasm of tumor cells in 59.3% of breast cancers. Expression of survivin was associated with high histologic grade (p = 0.027), high mitotic count (p = 0.014), positive p53 immunostaining (p = 0.012), neu overexpression (p = 0.018), and with bcl-2 (p = 0.001) and bak (p < 0.001) expression. No correlation was found between survivin expression and age, tumor size, estrogen receptor, progesterone receptor or Bax expression. Survivin expression was not significantly associated with overall or disease-free survival. CONCLUSIONS: Survivin expression is correlated with high histologic grade, high mitotic count, p53 overexpression, and bcl-2 expression in breast cancer. It does not have significance as a marker in predicting overall or disease-free survival.     

survivin、FHIT及bFGF在宫颈鳞癌组织中的表达及意义

目的:研究凋亡抑制基因survivin、抑癌基因FHIT及碱性成纤维细胞生长因子(bFGF)在正常宫颈组织、宫颈上皮内瘤变组织(CIN)及宫颈鳞癌组织中的表达及其与宫颈鳞癌临床分期、病理分级及淋巴结转移的关系,探讨其在宫颈鳞癌发生、发展中的作用。方法:分析郑州大学第二附属医院病理科2008年1月至2009年11月手术切除、病理检查证实为宫颈鳞癌的组织标本45例,另取CIN45例、正常宫颈组织15例(子宫肌瘤行子宫全切除术的宫颈组织)作为对照,应用免疫组化SP法检测survivin、FHIT及bFGF在3组宫颈组织中的表达情况。结果:sur-vivin在正常宫颈组织、CIN及宫颈鳞癌组织中的阳性表达呈上升趋势(χ2=11.429,P<0.05),survivin的表达在宫颈鳞癌不同临床分期、病理分级间比较,差异有统计学意义(P<0.05);FHIT在正常宫颈组织、CIN及宫颈鳞癌组织中的阳性表达呈下降趋势(χ2=24.640,P<0.05),FHIT的表达与宫颈鳞癌病理特征的关系中,仅在淋巴结有无转移方面比较差异有统计学意义(P<0.05);bFGF在正常宫颈组织、CIN及宫颈鳞癌组织中的阳性表达依次呈上升趋势(χ2=17.552,P<0.05),bFGF的表达在宫颈鳞癌不同临床分期、病理分级及淋巴结有无转移方面比较,差异均有统计学意义(P<0.05)。结论:survivin、FHIT、bFGF的表达与宫颈病变的进展有一定的关系,并且可能与宫颈鳞癌的发生、发展及浸润和转移有关。     

外阴癌中HPV感染与p53、MDM2表达的关系

目的 :探讨HPV6/ 11、16/ 18在外阴癌组织中的感染情况及与p5 3、MDM2蛋白表达的关系。方法 :用原位杂交法 (ISH)检测HPV6/ 11、16/ 18在 30例外阴癌、2 1例外阴上皮内瘤变 (VIN)及 10例外阴正常皮肤组织中的表达。同时用免疫组化SP法检测p5 3、MDM2蛋白的表达。结果 :HPV6/ 11、16/ 18在外阴癌、VIN中的阳性表达率分别为 60 % (18/30 )、33.33% (10 / 30 ) ,4 2 .86% (9/ 2 1)、2 8.5 7% (6/ 2 1) ,正常对照组没有表达。p5 3、MDM2蛋白在外阴癌、VIN、正常对照组中的阳性表达率分别为 63.33% (19/ 30 )、4 0 .0 0 % (12 / 30 ) ,4 7.62 %(10 / 2 1)、5 2 .38% (11/ 2 1) ,0 % (0 / 10 )、0 % (0 / 10 )。HPV6/ 11的表达在外阴癌组、VIN组与正常组差异有显著性 (P <0 .0 5 ) ,外阴癌组HPV16/ 18表达与正常组差异有显著性 (P <0 .0 5 )。外阴病变各组p5 3、MDM2与正常组差异有显著性 (P <0 .0 5 )。结论 :HPV6/ 11、HPV16/ 18、p5 3、MDM2蛋白在外阴组织的不同病变中表达均差异有显著性 ,在外阴癌的发生发展中HPV感染、p5 3突变和MDM2表达可能起一定的作用     

Survivin, a novel anti-apoptosis inhibitor, expression in uterine cervical cancer and relationship with prognostic factors

A novel inhibitor of apoptosis, Survivin, seems to be involved in the critical steps of cancer onset and progression and may be associated with unfavorable clinical outcome. We investigated the expression of Survivin in patients with cervical intraepithelial neoplasia grade 3 (CIN3) and uterine cervical cancer, to determine whether Survivin expression is related to poor prognosis. Fourteen cases of CIN3, 53 cases of invasive uterine cervical squamous cell carcinoma (SCC), and 11 cases of normal control group were analyzed retrospectively. Immunohistochemical staining and Western blot was performed with antihuman Survivin antibody and analyzed with respect to patient outcome. Survivin was significantly expressed in cervical cancer groups compared to the normal control group (P < 0.05). Significant Survivin expression was also noted in cancer patients with lesion size > or =4 cm, lymphovascular invasion, elevated SCC antigen levels, and no response to initial therapy. In more advanced stages, Survivin expression tended to increase but without statistical significance (P = 0.081). No association was noted between Survivin expression and survival rate (P = 0.1011). We conclude that Survivin expression provides some prognostic information regarding uterine cervical cancer, even though it was not correlated with survival. It could represent a possible new prognostic marker of uterine cervical SCC patients.     

Expression of survivin, PTEN and p27 in normal, hyperplastic, and carcinomatous endometrium

We aimed to investigate if expressions of survivin and p27 proteins are involved in the development of endometrioid carcinoma, along with whether there are any correlations between these proteins and loss of wild-type PTEN that is found in up to 80% of endometrial carcinomas. We also studied their correlations with classical prognostic factors and survival in endometrial carcinoma. To our knowledge, this is the first time survivin expression is investigated in endometrial hyperplasia along with endometrioid adenocarcinoma. For immunohistochemical analysis, 29 endometrioid adenocarcinoma, 38 endometrial hyperplasia, and 10 proliferative endometrium tissue samples were selected in the pathology archives. Staining of cells was scored as +2 if >50%, +1 if <50%, and negative if none were stained positive. Survivin expression increased from proliferative to hyperplasia to carcinoma cases. PTEN and p27 expressions decreased in hyperplasia and carcinoma cases with respect to proliferative endometrium. All these differences were statistically significant (P < 0.05). PTEN positively correlated to p27 (P < 0.05); however, neither was correlated with survivin. None of these genes were correlated with classical prognostic factors such as grade and myometrial invasion in endometrioid adenocarcinoma. However, mean survival was statistically significantly higher in PTEN-positive cases (46.6 vs 16.4 months) (P < 0.05). Survivin overexpression might be one of the important mechanisms in the development of endometrioid adenocarcinoma along with lost or decreased activity of PTEN and p27. However, survivin seems to exert its role in ways different from those of PTEN or p27 in the development of endometrioid adenocarcinoma. These findings on the role of survivin in endometrioid adenocarcinoma should be confirmed and the pathways through which survivin acts in endometrioid adenocarcinoma studied further with a larger sample size.     

Correlation between survivin expression and locoregional control in cervical squamous cell carcinomas treated with radiation therapy

OBJECTIVE: Survivin is a member of the inhibitors of apoptosis and has been implicated in both the regulation of cell division and the suppression of apoptosis. Over-expression of cytoplasmic survivin correlates with an unfavorable prognosis in many malignant tumors. However, the prognostic value of nuclear survivin expression is still equivocal. Here, we investigated the prognostic value of survivin expression in cervical cancer treated with radiation therapy. METHODS: Tissue sections were obtained from 72 patients with cervical squamous cell carcinoma treated with radiation therapy alone. Survivin expression levels were determined by immunohistochemical staining and evaluated for cell positivity. The correlation between survivin expression and clinical outcome endpoints including cause-specific survival and local control were evaluated. RESULTS: A total of 14% (10/72) of tissue specimens had greater than 5% nucleus positivity, while 47% (34/72) had greater than 50% cytoplasmic positivity. Local control rate of the cytoplasmic survivin-negative tumors was 94%, significantly higher than the 76% of the positive tumors (p=0.046). Local control rate of the nuclear survivin-positive and cytoplasmic survivin-negative patients was 95%, significantly higher than the 74% of the other patients (p=0.02). In contrast, no significant correlation was noted between survivin expression and disease-free survival. CONCLUSIONS: The cytoplasmic survivin expression alone and the combination of nuclear and cytoplasmic expression were suggested to be predictors for local control in patients with cervical squamous cell carcinoma treated with radiation therapy alone.     

The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions

OBJECTIVE: The purpose of this study was to assess the expression and clinical significance of bcl-2 and p53 in the progression of cervical neoplasias. METHODS: One hundred seventy-one cervical specimens, consisting of normal cervical epithelium (n = 13), lesions with histological features of HPV infection (n = 14), CIN (cervical intraepithelial neoplasia) lesions (n = 63), and cervical carcinomas (n = 81) were examined immunohistochemically in paraffin sections. RESULTS: Twenty-three specimens showed p53 expression [3/20 (15%) CIN III, 18/63 (29%) ISCC (invasive squamous cervical carcinoma), and 2/18 (11%) adenocarcinomas] while 63 cases expressed the bcl-2 gene [10/13 (77%) normal, 0/14(0%) condylomas, 6/23 (26%) CIN I, 9/20 (45%) CIN II, 15/20 (75%) CIN III, 18/63 (29%) ISCC, and 5/18 (28%) adenocarcinomas]. The expression of bcl-2 was found to increase in direct relation to the grade of CIN (P = 0.02) whereas such a trend was not observed for p53. p53 was not detected in normal or premalignant lesions (except 3 out of 20 cases of CIN III). There was no significant correlation between the expression of p53 and the histological type of cervical carcinoma, even though expression of p53 was higher in ISCC than in adenocarcinomas (29% vs 11%, respectively). In cervical cancer patients, expression of bcl-2 was correlated to a greater than 5-year survival (P < 0.01) while no prognostic significance of p53 expression was found. CONCLUSION: Evaluation of bcl-2 expression may provide additional and independent prognostic information for the clinical course of the disease and therefore to be developed as a prognostic indicator for cervical cancer.     

宫颈癌中survivin、ki67、cyclinB1的表达及临床意义

目的 :检测survivin、ki6 7、cyclinB1在宫颈癌中的表达 ,探讨它们与宫颈癌组织增殖、细胞周期与凋亡的关系。方法 :应用免疫组化SABC、SP法。结果 :(1)宫颈癌中survivin、ki6 7、cyclinB1表达显著高于正常宫颈组织 (P <0 .0 1) ;(2 )survivin表达与年龄、临床分期和淋巴结转移有关 ,但与宫颈癌组织细胞类型及分化程度无明显相关性。ki6 7表达只与临床分期有关 ,与年龄、组织细胞类型、淋巴结转移及分化程度无明显相关关系。cyclinB1表达与临床病理特征之间无明显相关性 ;(3)宫颈癌组织中survivin表达与ki6 7、cyclinB1表达显著相关。结论 :survivin、ki6 7、cyclinB1异常表达与宫颈癌显著相关 ,宫颈癌的发生与凋亡抑制和增殖能力增强有关。     

Survivin、Bcl-2、HPV 16/18在宫颈上皮内瘤变及宫颈癌中的表达及临床意义

目的:研究Survivin、Bcl-2、HPV 16/18在宫颈上皮内瘤变(CIN)及宫颈癌中的表达,探讨三者与宫颈癌的相关性.方法:采用原位杂交法检测正常宫颈组织(对照组)、CIN(CIN组)和宫颈癌(宫颈癌组)中Survivin mRNA及HPV 16/18 DNA的表达.采用免疫组织化学法检测Bcl-2蛋白在各组中的表达.结果:①Bcl-2蛋白、HPV16/18DNA、Survivin mRNA的阳性率在对照组、CIN组、宫颈癌组中逐渐升高,差异有高度统计学意义(P=0.000).②Bcl-2蛋白和Survivin mRNA在宫颈癌的组织分化程度中,低分化组的表达高于高、中分化组(P<0.01),ⅡB～Ⅲ期显著高于I～ⅡA期(P<0.05);Survivin mRNA在淋巴结转移组中高于无淋巴结转移组(P<0.01);Survivin mRNA及Bcl-2与组织类型及肿块类型无关(P>0.05);HPV 16/18感染与宫颈癌组织类型、组织分化程度、临床分期、肿块类型均无关(P>0.05).(③Survivin与Bcl-2及HPV 16/18在宫颈癌中的表达均呈正相关.结论:Survivin、Bcl-2及HPV 16/18在宫颈癌中有异常表达.三者可能与宫颈癌的发生发展有密切关系.