48例阴式扩大性子宫颈切除术临床分析

目的探讨阴式扩大性宫颈切除术保守性治疗Ⅰa1期宫颈鳞癌及不适于行宫颈锥切术的宫颈上皮内瘤变（CIN）Ⅲ级患者的可行性及安全性。方法2002年7月-2007年5月,选择经环形电切术（LEEP）并活检后病理诊断的宫颈鳞癌Ⅰa1期（除外脉管癌栓）、大面积CINⅢ（阴道镜下病变面积≥3／4）、CINⅢ合并阴道上段上皮内瘤变（VAIN）、CINⅡ-Ⅲ锥切术后或LEEP术后复发、病变残存、切缘阳性,且要求保留子宫和（或）生育功能的患者,行阴式扩大性宫颈切除术治疗,对其临床资料进行分析。结果48例患者顺利实行阴式扩大性宫颈切除术,其中Ⅰa1期宫颈鳞癌患者5例,大面积CINⅢ患者38例（9例累及腺体）,CINⅢLEEP术后病变残存2例、切缘阳性2例,CINⅡ锥切术后复发1例。患者年龄27-40岁,中位年龄34岁,平均手术时间60min（30-100min）,平均出血量加ml（5-300ml）,平均住院天数10d（7-17d）。随访1～39个月,随访时间的中位数为14个月,无术后并发症及复发病例。结论阴式扩大性宫颈切除术是一种保守性治疗Ⅰa1期宫颈鳞癌、大面积CINⅢ、CINⅢ合并VAIN以及CINⅡ-Ⅲ锥切术后复发、病变残存、切缘阳性等不适于行宫颈锥切术患者的、安全有效的术式。     

p16INK4A、p53、Ki-67及ER在宫颈病变组织中的表达及其相关性研究

目的 探讨p16INK4A、p53、Ki-67及雌激素受体(ER)在不同程度宫颈病变中表达及相关性.方法 采用SP法检测宫颈鳞状细胞癌、宫颈上皮内瘤变(CIN)、尖锐湿疣及正常宫颈组织中p16INK4A、p53、Ki-67及ER蛋白的表达.结果 p16INK4A、p53、Ki-67及ER在宫颈鳞癌组中的阳性率分别为100%、86.4%、86.4%及4.6%;在CIN Ⅲ中为92.5%、75.0%、100%、20.0%;在CIN Ⅱ中为90.5%、64.3%、100%及23.9%;在CINⅠ中为71.8%、43.6%、100%、79.5%;在尖锐湿疣组中为39.0%、43.9%、26.9%、61.0%.p16INK4A在宫颈鳞癌、CIN Ⅲ、Ⅱ组中,以强阳性表达为主;尖锐湿疣组仅为弱阳性表达.Ki-67在宫颈鳞癌、CINⅢ组中,以强阳性表达为主.宫颈鳞癌、CINⅢ、Ⅱ、Ⅰ、尖锐湿疣中p16INK4A、p53、Ki-67、ER阳性表达率与对照组比较差异有高度显著性(P＜0.05).结论 p161NK4A、p53蛋白高表达与宫颈鳞癌、CIN的发生发展密切相关;p16INK4A、p53、Ki-67阳性率与宫颈病变严重程度呈正相关,ER的阳性率与其呈负相关.     

DNA倍体分析联合高危型人乳头瘤病毒检测筛查宫颈病变

目的:探讨DNA倍体分析联合高危型人乳头瘤病毒(HPV)检测对宫颈上皮内瘤变(CIN)Ⅱ级及以上的宫颈病变(CINⅡ+CINⅢ+宫颈癌,以下简称CINⅡ+)的诊断价值。方法:对502例宫颈癌筛查患者同时行宫颈薄层液基细胞学检查(TCT)、细胞DNA倍体分析及高危型HPV检测,对检测异常者进行阴道镜下宫颈活检组织检查,以病理结果为金标准,对比分析TCT、DNA倍体分析、TCT联合高危型HPV检测及DNA倍体分析联合高危型HPV检测对CINⅡ+的诊断价值。结果:TCT对CINⅡ+敏感度为52.17%,特异度为98.24%;DNA倍体分析对CINⅡ+敏感度为78.26%,特异度为90.93%;TCT联合高危型HPV检测对CINⅡ+敏感度为100.00%,特异度为92.70%;DNA倍体分析联合高危型HPV检测对CINⅡ+敏感度为91.30%,特异度为92.19%。结论:DNA倍体分析联合高危型HPV检测是筛查CINⅡ+的有效方法,有一定的临床应用价值,尤其适合在医疗资源缺乏的地区实施。     

子宫颈人乳头状瘤病毒感染的流行病学特征

人乳头状瘤病毒 (HPV)是一种无包膜的小DNA病毒 ,具有强烈嗜上皮性、高度组织和宿主特异性 ,可致人类皮肤和黏膜异常增生。目前 ,已知的HPV有 10 0多种 ,其中 30余种可从受感染的生殖道组织中分离出来。根据病毒致癌性的大小分为两大类 :(1)低危型HPV(非癌相关型 ,LRHPV) :包括HPV6、11、4 2、4 3和一些新型HPV ;感染LRHPV ,可导致轻度宫颈上皮内瘤样变 (CINⅠ )和部分中度宫颈上皮内瘤样变(CINⅡ ) ,HPVDNA常为二倍体和多倍体 ,这种病变多能自行消退 ,几乎未见到感染LRHPV者发展为重度宫颈上皮内瘤样变 (CINⅢ )或宫颈…     

子宫颈上皮内瘤变端粒酶活性的研究

目的探讨端粒酶激活在宫颈癌变过程中的意义及其作为病情监测方法和预测宫颈上皮内瘤变(CIN)结局的可能性.方法采用端粒重复序列扩增-聚合酶链反应(PCR-TRAP)方法检测了64例CIN患者、21例宫颈癌患者、20例慢性宫颈炎患者及15例正常宫颈妇女宫颈脱落细胞、宫颈活组织检查(活检)组织的端粒酶活性.结果正常宫颈、慢性宫颈炎、CINⅠ级(CINⅠ)、CINⅡ级(CINⅡ)、CINⅢ级(CINⅢ)及宫颈癌患者的宫颈脱落细胞端粒酶的阳性表达率分别为20.0%、25.0%、62.5%、60.0%、82.4%及61.9%;对应的活检组织端粒酶的阳性表达率分别为26.7%、30.0%、50.0%、45.0%、96.4%及95.2%;随着宫颈病变的进展,端粒酶阳性表达率呈逐渐增高趋势(X2细胞=16.28、X2组织=36.98,P均＜0.05).CINⅠ、CINⅡ端粒酶阳性表达率比较,差异无显著性(P细胞=0.24、P组织=0.25);CINⅢ端粒酶阳性表达率高于CINⅠ、CINⅡ(P细胞=0.03、P组织=0.000012);CINⅢ与宫颈癌活检组织端粒酶阳性表达率比较,差异无显著性(P=0.05);宫颈脱落细胞与宫颈活检组织的端粒酶检测结果的对应性良好(X2=46.4,P＜0.05).结论端粒酶激活与宫颈癌变的进程有关,宫颈脱落细胞端粒酶活性检测可以作为CIN病情检测、处理及预后估计的辅助指标.     

妊娠期宫颈上皮内瘤变的筛查和处理进展

宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)包括了宫颈癌的所有癌前病变和原位癌,根据病变程度分为Ⅰ、Ⅱ、Ⅲ级.     

DNA倍体图像分析用于评价宫颈非典型不成熟化生

目的:探讨DNA图像分析技术在评价宫颈非典型不成熟化生(AIM)生物学性质中的作用。方法:运用计算机图像分析软件测定宫颈非典型不成熟化生30例的DNA质量、非整倍体(AN)含量、DNA指数(DI),以40例良、恶性宫颈病变为对照,其中正常上皮组10例,CINⅠ组10例,CINⅢ组10例,宫颈鳞癌组10例。结果:DNA质量、非整倍体含量、DNA指数随病变严重程度的增加而升高,三者联合分析有助于评价病例的生物学性质,从30例宫颈非典型不成熟化生病例中筛选出2例,其DNA质量、非整倍体含量、DNA指数均达到CINⅢ组的均值水平,认为是高恶性潜能病例。结论:计算机分析技术方便客观,通过综合分析DNA质量、非整倍体含量和DNA指数有助于提示宫颈非典型不成熟化生病例的生物学性质,对高恶性潜能病例具有筛查作用。     

P16和Ki-67在宫颈上皮内瘤变组织中的表达及意义

目的研究P16和Ki-67在宫颈上皮内瘤变组织中的表达及与高危型人乳头瘤病毒(HPV)的关系和临床意义。方法应用免疫组织化学方法检测2005年9月至2007年8月间广东省人民医院40例正常宫颈组织、103例宫颈上皮内瘤变(CIN)及56例宫颈浸润癌中P16和Ki-67的表达,并采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPVDNA。结果P16和Ki-67的表达强度与CIN的严重程度分别呈正相关(P<0.01)。P16和Ki-67在CINⅡ、CINⅢ、宫颈鳞癌及腺癌中表达呈阳性至强阳性的比例,明显高于正常宫颈组织及CINⅠ,差异有统计学意义(P<0.01)。高危型HPV感染阳性率88.9%(177/199),其中正常宫颈42.5%、CINⅠ87.5%、CINⅡ与CINⅢ均100%、宫颈鳞癌98.0%、腺癌60.0%。高危型HPVDNA负荷量与P16、Ki-67的表达强度分别呈正相关(P<0.01)。结论P16和Ki-67的表达强度与CIN的严重程度以及高危型HPVDNA负荷量密切相关;P16和Ki-67可作为诊断CINⅡ及CINⅢ的重要辅助指标。     

宫颈癌前病变与宫颈鳞癌组织中Foxp3的表达及临床意义

目的 观察宫颈鳞癌及癌前病变组织中Foxp3的表达情况.方法 采用免疫组化检测浸润性宫颈鳞癌(FIGOⅠ期或ⅡA期,共20例)、宫颈上皮内瘤样病变(CIN1、CIN2、CIN3各20例)、宫颈HPV感染(20例)及正常宫颈(20例)组织中Foxp3的表达情况.结果 浸润性宫颈鳞癌与CIN3患者宫颈组织中Foxp3表达明...     

吲哚胺2,3-二氧酶在CIN及宫颈鳞癌中的表达及其意义

目的:探讨吲哚胺2,3-二氧酶(indoleamine 2,3-dioxygenase,IDO)在宫颈上皮内瘤变(CIN)及宫颈鳞癌中的表达及意义.方法:选择经病理确诊为CIN Ⅰ～CIN Ⅲ和宫颈鳞癌患者的石蜡标本116例,以同时期因子宫肌瘤行全子宫切除患者的正常宫颈组织石蜡标本20例作为对照,采用免疫组化方法检测宫颈CIN及宫颈鳞癌中IDO表达情况.结果:正常宫颈组织和CIN Ⅰ,CIN Ⅱ～CIN Ⅲ,宫颈鳞癌ⅠA期～ⅠB期,ⅡA期～ⅣB期4组之间IDO阳性表达强度差异有高度统计学意义(P＜0.01).在宫颈鳞癌Ⅰ～Ⅳ期IDO总阳性表达率为100%,ⅠA期～ⅠB期IDO总阳性表达率显著高于CIN Ⅱ和CIN Ⅲ(P＜0.01),ⅡA～ⅣB期IDO阳性表达强度显著高于ⅠA期～ⅠB期(P＜0.01).IDO表达与宫颈鳞癌进展有关(OR=0.779,JP＜0.01);在宫颈鳞癌淋巴转移阳性组IDO阳性表达强度显著高于淋巴转移阴性组(P＜0.01);IDO表达与肿瘤分化程度无相关性(P＞0.05).结论:从CIN Ⅱ开始,肿瘤组织已逐步建立起有利于肿瘤发展的免疫逃逸机制.IDO的表达与疾病进展有关而与肿瘤组织分化程度无关,IDO可能成为宫颈鳞癌预后的预测因子及治疗靶点.     

PCNA在宫颈鳞癌组织中的表达及意义

目的探讨细胞核增值抗原（proliferating cell nuclear antigen,PCNA）在宫颈鳞癌和宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）组织中的表达及意义。方法采用免疫组织化学S-P法检测92例宫颈鳞癌、40例CIN和92例宫颈正常组织的PCNA蛋白表达情况。结果宫颈鳞癌组织PCNA阳性表达率为82.61%（76/92）;CINⅠ、CINⅡ和CINⅢPCNA阳性表达率分别为33.33%（5/15）、71.43%（10/14）和81.82%（9/11）,正常宫颈组织无PCNA表达。宫颈鳞癌、CINⅡ和CINⅢ组织PCNA阳性表达率明显高于CINⅠ（P〈0.01）;但宫颈鳞癌PCNA表达与CINⅡ、CINⅢ比较,差异无统计学意义（P〉0.05）。PCNA阳性表达与宫颈癌分期（r=0.634,P〈0.01）、组织学分级（r=0.654,P〈0.05）有关;而与年龄无关（r=0,P〉0.05）。结论 PCNA的阳性表达可能与宫颈癌的发生、发展及细胞增殖活性增加有关。     

Decreased expression of the CDK inhibitor p27Kip1 and increased oxidative DNA damage in the multistep process of cervical carcinogenesis

OBJECTIVE: The expression of the CDK inhibitor p27Kip1 and the extent of endogenous oxidative DNA damage were evaluated in the multistep cervical carcinogenesis. METHODS: Archival specimens of low-grade (L) squamous intraepithelial lesions (SILs) (n=32), high-grade (H) SILs (n=24) and invasive carcinomas (n=48) of the cervix were included in the analysis compared with normal cervical squamous epithelium (n=15). Expression level of p27Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues. RESULTS: p27Kip1 was constantly expressed in normal epithelium with a mean percentage of positive cells higher than 50%. A progressive significant reduction in the mean percentage of positive cells was observed in L-SIL (18.1%), H-SIL (7.3%) and in invasive carcinomas (2.5%). A progressive significant increase in the levels of 8-OHdG and in the percentage of mean positive cells was observed from L-SIL (2.2%) to H-SIL (12.5%) to invasive carcinomas (25.2%). p27Kip1 and 8-OHdG expression displayed a significant inverse relationship. CONCLUSIONS: Expression of p27Kip1 is down-regulated while oxidative DNA damage increases during cervical carcinogenesis. Both parameters are altered at early stages of the process and might help to predict patients at high risk of progression.     

Microcytomorphometric video-image detection of nuclear chromatin in ovarian cancer

Technology of detection of tissue preparates precisious evaluates contents of nuclear chromatine, largeness and shape of cellular nucleus, indicators of mitosis, DNA index, ploidy, phase-S fraction and other parameters. Methods of detection of picture are: microcytomorphometry video-image (MCMM-VI), flow, double flow and activated by fluorescence. Diagnostic methods of malignant neoplasm of ovary are still nonspecific and not precise, that is a reason of unsatisfied results of treatment. OBJECTIVE: Evaluation of microcytomorphometric measurements of nuclear chromatine histopathologic tissue preparates (HP) of ovarian cancer and comparison to normal ovarian tissue. MATERIAL AND METHODS: Estimated 10 paraffin embedded tissue preparates of serous ovarian cancer, 4 preparates mucinous cancer and 2 cases of tumor Kruckenberg patients operated in Clinic of Perinatology and Gynaecology Silesian Medical Academy in Zabrze in period 2001-2002, MCMM-VI estimation based on computer aided analysis system: microscope Axioscop 20, camera tv JVCTK-C 1380, CarlZeiss KS Vision 400 rel.3.0 software. Following MCMM-VI parameters assessed: count of pathologic nucleus, diameter of nucleus, area, min/max diameter ratio, equivalent circle diameter (Dcircle), mean of brightness (mean D), integrated optical density (IOD = area x mean D), DNA index and 2.5 c exceeding rate percentage (2.5 c ER%). MCMM-VI performed on the 160 areas of 16 preparates of cancer and 100 areas of normal ovarian tissue. Statistical analysis was performed by used t-Student test. RESULTS: We obtained stastistically significant higher values parameters of nuclear chromatine, DI, 2.5 c ER of mucinous cancer and tumor Kruckenberg comparison to serous cancer. MCMM-VI parameters of chromatine malignant ovarian neoplasm were statistically significantly higher than normal ovarian tissue. CONCLUSION: Cytometric and karyometric parametres of nuclear chromatine estimated MCMM-VI are useful in the diagnostics and prognosis of ovarian cancer.     

Expression of cyclooxygenase-2 in cervical,endometrial, and ovarian malignancies

OBJECTIVE: This study was undertaken to compare the presence of cyclooxygenase-2 (COX-2) levels between normal and malignant cervix, endometrium, and ovary. STUDY DESIGN: Semiquantitative immunofluorescent assays for COX-2 were performed on sections of cervical squamous cell carcinoma (n = 12), endometrial adenocarcinoma (n = 13), and ovarian serous adenocarcinoma (n = 9). Levels of immunofluorescence for each sample were objectively measured, categorized as high, moderate, or negative expression and compared with normal cervical (n = 14), endometrial (n = 15), and ovarian (n = 13) tissue with the Fisher exact test. RESULTS: Normal cervical tissue expressed COX-2 more frequently than cervical cancer (50% vs 23%), but the difference was not significant (P =.247). COX-2 was rarely present in normal endometrium (7%) and normal ovarian epithelium (0%) and was usually present in endometrial adenocarcinoma (69%, P <.001) and ovarian serous cystadenocarcinoma (89%, P <.001). CONCLUSION: In this cohort, COX-2 expression is significantly more common in endometrial adenocarcinoma and ovarian serous cystadenocarcinoma, but not in cervical squamous carcinoma, compared with normal tissue.     

细胞凋亡和P53在宫颈癌及宫颈上皮内瘤变中的表达

目的：探讨细胞凋亡和P53在宫颈癌及宫颈上皮内瘤变中的作用。方法：用DNA缺口末端标记技术(TUNEL)和免疫组化技术原位观察15例正常宫颈、22例CIN*"I/Ⅱ、16例CINⅢ和52例浸润性宫颈鳞癌(ISCC)组织中细胞凋亡标记指数(A-LI)、PCNA(增殖细胞核抗原)标记指数(PCNA-LI)和P53表达阳性率及P53标记指数(P53-LI)。结果：在正常宫颈上皮未检测到凋亡细胞,随着CIN病变的进展,A-LI增高(P＜005),在ISCC,A-LI明显低于CIN(P＜001);PCNA-LI随宫颈癌各级病变的进展逐渐增高(Ｐ＜005);在正常宫颈和CINI/Ⅱ均未检测到P53表达,在CINⅢ,P53-LI明显低于ISCC(P＜001)。结论：细胞凋亡在宫颈癌发生发展过程中发挥重要作用,P53蛋白的积聚可能对细胞凋亡起抑制作用。     

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.     

Quantitative pathologic features as predictors of long-term survival in patients with advanced ovarian cancer treated with cisplatin

The prognostic value of morphometric and DNA flow cytometric features were studied and compared with FIGO stage, preoperative tumor load, residual disease status, Karnofsky index and classic pathologic features such as Broders' grade and histologic type in 58 FIGO stage III and IV adequately debulked ovarian patients with long-term follow-up. The mitotic activity index, volume percentage of epithelium, and mean and SD of nuclear area were assessed by interactive morphometry, and tumor material was routinely processed for DNA flow cytometric assessment of DNA ploidy and S-phase fraction. Survival analysis (Kaplan-Meier curves, Mantel-Cox test), revealed FIGO stage ( P = 0.013) and the mean and SD of nuclear area to be significant prognosticators ( P = 0.027 and P = 0.012, respectively). In multivariate survival analysis (Cox model), a multivariate combination of FIGO stage, preoperative tumor load and mean nuclear area was the best prognostic combination of features ( P = 0.0034). These results confirm the findings of previous studies. We conclude that, in accord with previous studies, morphometric features are good predictors of survival after cisplatin treatment in advanced ovarian cancer, especially in combination with FIGO stage and preoperative tumor load.     

The role of p53, Bcl-2 and Ki-67 in premalignant cervical lesions and cervical cancer

PURPOSE: The aim of this study was to determine the role of p53, Bcl-2 and Ki-67 expression in the carcinogenesis of cervical carcinoma and aggressiveness of cervical intraepithelial neoplasia (CIN). METHODS: The pathology specimens of 63 patients with a diagnosis of normal squamous epithelium (22 cases), CIN I (14), CIN II (5), CIN III (8) and squamous cell carcinoma (14) were evaluated immunohistochemically for the expression of p53, Bcl-2 and Ki-67 in paraffin sections. RESULTS: The expression of p53 and Ki-67 increased proportionally to the grade of CIN and cervical cancer, but only the increase of p53 expression was statistically significant (p = 0.002). There was no significant correlation between Bcl-2 expression and premalignant and malignant cervical lesions. CONCLUSION: p53 expression may have a role in the carcinogenesis of squamous cell cervical carcinoma whereas Bcl-2 expression has no role. Ki-67 expression can not be used in determining the aggressiveness of CIN lesions.     

透明质酸在宫颈上皮及宫颈癌组织中的表达

目的 :探讨透明质酸 (HA)在正常宫颈上皮及宫颈癌中的表达及其与肿瘤发生发展的关系。方法 :用免疫组化法检测 5 9例宫颈浸润癌、35例宫颈上皮内瘤样病变 (CIN)及11例正常宫颈组织中HA和CD4 4v6的表达。结果 :正常宫颈上皮不表达HA。慢性炎症者上皮底层细胞以及细胞间质表达HA ,随病变加重及CIN发生 ,HA表达增强。癌旁组织的上皮细胞HA呈强阳性表达 ,伴有基质HA强阳性染色。癌细胞HA阳性率为 6 7.2 7% ,与病理类型有关 ,角化癌高表达 ,而腺癌不表达 ,在低分化鳞癌中多见不规则灶性HA阴性区。宫颈鳞癌的肿瘤基质HA表达普遍增强。肿瘤基质的HA表达与CD4 4v6呈正相关。结论 :正常宫颈上皮不表达HA ,但炎症与致瘤因素可促使HA表达 ,HA的代谢失衡可能与宫颈癌的发生及浸润行为有关