自制组织芯片检测宫颈上皮内瘤变中p16蛋白的表达

目的:研究p16蛋白在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)中的表达及探讨其辅助诊断价值.方法:利用自制组织芯片进行184例CIN病变上皮和30例正常上皮HE光镜观察和免疫组化检测p16蛋白表达.结果:①自制组织芯片切片染色满意,达到较大标本量研究要求;②p16蛋白在10例正常对照和20例病变组织中的正常鳞状上皮与腺上皮均阴性表达,在CIN1中为88.1%(52/59),在CIN 2、CIN 3中均为100.0%表达,且表达的强度与CIN分级明显相关,有显著统计学意义(P＜0.001).CIN 1大部分阳性细胞限于上皮层的下1/3,CIN 2限于上皮的下2/3,而CIN 3则较多超过上皮的2/3或全层弥漫阳性,其表达层次与CIN分级明显相关,有显著统计学意义(P＜0.001).结论:在宫颈CIN的诊断及分级中,p16蛋白作为辅助诊断标记物有较好的应用价值;而自制的组织芯片成本低,质量上能达到科研要求,值得基层单位应用.     

宫颈环形电刀切除术治疗212例宫颈上皮内瘤变价值探讨

目的:探讨宫颈环形电刀切除术(LEEP)治疗宫颈上皮内瘤变(CIN)的价值。方法:回顾分析2000年3月至2004年10月212例CIN患者在阴道镜辅助下行宫颈环形电切术的治疗情况。结果:阴道镜下宫颈异常结构处取活检病理结果为CIN者212例行宫颈环形电切术(LEEP),LEEP术后病理检查:宫颈粘膜慢性炎症13例(6.1%)、CINⅠ90例(42.5%)、CINⅡ77例(36.3%)、CINⅢ24例(11.3%),原位癌累及腺体伴早期浸润癌8例(3.8%)。术后195例(92.0%)宫颈标本边缘病理学检查未见CIN病变;术后降级者70例(33.0%),等级者122例(57.5%),升级者20例(9.4%);治愈率达89.2%。结论:LEEP治疗CIN安全有效、简单易行、并发症少、避免了二次手术和过度治疗,能保留患者的生育能力,在治疗的同时能进行诊断。但术后仍需定期和规范的随访以防止宫颈癌的发生和发展。     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

Chronic inhalation exposure to mainstream cigarette smoke increases lung and nasal tumor incidence in rats.

An animal model of lung carcinogenicity induced by chronic inhalation of mainstream cigarette smoke would be useful for research on carcinogenic mechanisms, smoke composition-response relationships, co-carcinogenicity, and chemoprevention. A study was conducted to determine if chronic whole-body exposures of rats would significantly increase lung tumor incidence. Male and female F344 rats (n = 81 to 178/gender) were exposed whole-body 6 h/day, 5 days/week for up to 30 months to smoke from 1R3 research cigarettes diluted to 100 (LS) or 250 (HS) mg total particulate matter/m(3), or sham-exposed to clean air (C). Gross respiratory tract lesions and standard lung and nasal sections were evaluated by light microscopy. A slight reduction of survival suggested that the HS level was at the maximum tolerated dose as commonly defined. Cigarette smoke exposure significantly increased the incidences of non-neoplastic and neoplastic proliferative lung lesions in females, while nonsignificant increases were observed in males. The combined incidence of bronchioloalveolar adenomas and carcinomas in females were: HS = 14%; LS = 6%; and C = 0%. These incidences represented minima because only standard lung sections and gross lesions were evaluated. Mutations in codon 12 of the K-ras gene occurred in 4 of 23 (17%) tumors. Three mutations were G to A transitions and one was a G to T transversion. The incidence of neoplasia of the nasal cavity was significantly increased at the HS, but not the LS level in both males and females (HS = 6%, LS = 0.3%, C = 0.4% for combined genders). These results demonstrate that chronic whole-body exposure of rats to cigarette smoke can induce lung cancer.     

Ki-67抗原与CDK8在宫颈癌及宫颈上皮内瘤变中的表达及临床意义

目的：探究Ki-67抗原与细胞周期依赖性蛋白激酶8（CDK8）在宫颈癌和宫颈上皮内瘤变中的表达和临床意义。方法选取宫颈癌患者64例,宫颈上皮内瘤变（CIN）患者138例,并对其进行分级分期,同时选取正常妇女宫颈组织50例,运用免疫组化方法检测所纳入研究病例宫颈组织Ki-67抗原与CDK8的表达水平。结果Ki-67与CDK8在正常宫颈、宫颈癌、CIN中的阳性率比较,差异均有统计学意义（P﹤0.05）;Ki-67与CDK8在宫颈癌各分化程度间,各临床分期间的阳性率比较,差异均有统计学意义（P﹤0.05）;Ki-67与CDK8在鳞癌中的阳性率与腺癌比较,及在有无淋巴结转移宫颈癌中的阳性率比较,差异均有统计学意义（P﹤0.05）。结论 Ki-67抗原及CDK8与宫颈癌、CIN的病变程度存在一定的关系,检测其表达水平和强弱可能有助于预测宫颈高度病变的转归。     

AEG-1在宫颈癌组织中的表达及临床意义

目的探讨AEG-1在宫颈癌中的表达情况及其与临床病理特征的关系。方法应用免疫组织化学sP法检测21例正常宫颈组织、36例宫颈鳞状细胞癌组织、18例宫颈腺癌组织和30例宫颈上皮内瘤样病变（CIN）组织中AEG-1蛋白的表达,并分析其与临床病理特征及肿瘤恶性程度间的关系。结果AEG-1蛋白在宫颈鳞癌和宫颈腺癌组织中的阳性表达率分别为69．4％和72．2％,高于其在CIN组织和正常宫颈组织中40．0％、0．0％的表达率,其差异具有统计学意义（P〈0．05）。AEG-1的阳性表达与宫颈癌临床分期、淋巴结转移、病灶大小、脉管浸润及肌层浸润密切相关,有统计学意义（P〈0．05）;与宫颈癌的组织学分级、组织学分型及年龄无关（P〉0．05）。结论AEG-1过表达与宫颈癌的发生、发展密切相关,AEG-1的过表达可作为预测宫颈癌恶性程度和不良预后的重要指标。     

Neither one‐time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993–1994. At the enrollment visit, we applied multiple state‐of‐the‐art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5–7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow‐up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen‐positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under‐screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer. © 2009 UICC     

子宫颈鳞癌和CIN中HPV、EBV感染及其对抗原递呈细胞的影响

目的:探讨人乳头瘤病毒(human papillomavirus,HPV)、EB病毒(Epstein-Barr virus,EBV)在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈浸润性鳞状细胞癌(cervical invasive squamous cellcarcinoma,CISCC)中感染状况,及其对抗原递呈细胞的影响。方法:选择CIN和CISCC为实验组并与正常鳞状上皮做对照,用原位杂交(In situ hybridization,ISH)技术检测HPV-DNA,用免疫组化SP法标记EBV和郎格罕斯细胞(Langerhans celles,LC)。结果:HPV-DNA从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组,阳性率依次为0、60.0%、70.0%、78.0%和56.7%,组间存在显著性差异(P<0.005);并且各级CIN和CISCC组明显高于正常宫颈鳞状上皮(P<0.005~0.01);CINⅢ与CISCC之间存在显著差异(P<0.005)。EBV仅在CIN和CISCC中见到极少数弱阳性细胞。LC从正常、CINⅠ、CINⅡ、CINⅢ到CISCC组,阳性率依次为20.0%、71.4%、55.0%、76.5%和92.9%。S-100蛋白在各级别CIN及CISCC中表达均明显高于正常宫颈鳞状上皮(P<0.005);CISCC明显高于各级别CIN(P<0.005)。结论:随CIN级别升高到CISCC,HPV-DNA检出率并不增高,说明HPV感染引发宫颈癌的作用,可能是早期事件,提示妇科病理工作中,在CIN早期检测HPV更有意义。EBV在CIN及CISCC组织中几乎不存在。LC阳性率从正常宫颈上皮、CIN到CISCC,呈逐渐增高趋势。在CIN和CISCC中病毒感染和LC阳性率呈正相关,说明HPV感染可导致LC增多,实际工作中检测LC对了解HPV感染有一定的辅助意义。     

Effectiveness of novel,lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china

This study examined the efficacy of the OncoE6? Cervical Test, careHPV? and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ～10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ～10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV? on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6? test. The OncoE6? test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.     

宫颈环形电切术治疗宫颈上皮内瘤样病变238例

目的 观察宫颈环形电切术治疗Ⅱ～Ⅲ级、Ⅲ级宫颈上皮内瘤样病变(CIN)的临床疗效及其安全性.方法 回顾性分析经阴道镜下活检诊断为Ⅱ～Ⅲ级、Ⅲ级CIN的238例患者的临床资料.均采用宫颈环形电切术(LEEP)行宫颈锥形切除,观察手术后感染和出血、病灶残留情况,随访手术治疗效果和复发情况,随访观察高危型人类乳头瘤病毒(HPV)感染持续及其转阴时间.结果 术后发生宫颈感染21例(8.82%),术后平均出血时间为9 d;术后发生病灶残留25例(10.50%);术后平均随访时间20个月,复发9例(3.78%);术后高危型HPV感染持续平均时间为7个月.结论 宫颈环形电切术在切除高级别CIN病变的同时,还能有效清除高危型HPV感染,用于治疗宫颈上皮内瘤变是安全有效的.