水通道蛋白5过表达与宫颈癌发生及临床病理特征的相关性

目的：研究水通道蛋白5（aquaporin 5,AQP5）在宫颈癌中的表达及临床病理意义,探讨AQP5在宫颈组织恶性转化过程中的可能作用。方法：采用蛋白质免疫印迹和免疫组织化学技术检测30例正常宫颈、28例宫颈上皮内瘤样变（CIN）和56例宫颈鳞状细胞癌组织中AQP5的表达,并对其表达的临床病理参数进行统计学分析。结果：AQP5在正常宫颈、CIN和宫颈癌组织中相对蛋白表达量逐渐升高,3组间差异有统计学意义（F=38.516,P=0.000）;其表达的平均阳性细胞百分比分别为15.12%、23.18%和36.08%,3组间差异有统计学意义（χ2=22.404,P=0.000）;AQP5过表达与宫颈癌淋巴结转移相关（r=0.351,P=0.008）,与患者年龄、肿瘤大小、组织学分级和国际妇产科联盟（FIGO）分期无关。结论：增强的AQP5表达与正常宫颈组织恶性转化和宫颈癌发生有关,有望为宫颈癌提供一种新的治疗靶点和预后标记。     

高迁移率蛋白A2在不同宫颈病变中的表达及意义

目的探讨高迁移率蛋白A2(HMGA2)在不同宫颈病变组织中的表达及其临床意义,了解其与宫颈人乳头瘤病毒(HPV)感染的关系。方法免疫组织化学法检测无锡市第三人民医院2005至2007年30例正常宫颈组织、19例低级别上皮内瘤样病变宫颈组织、16例高级别上皮内瘤样病变宫颈组织、13例宫颈鳞癌组织中HMGA2蛋白的表达,原位杂交检测各组织中HPV感染的情况,分析HMGA2蛋白表达与HPV感染在宫颈病变组织中的相关性。结果正常宫颈组织、CINⅠ级、CINⅡ~Ⅲ级和宫颈浸润性鳞癌组织中,HMGA2蛋白的阳性表达率分别为26.67%、21.05%、68.75%和76.92%。CINI与正常宫颈组织阳性表达率比较,差异无统计学意义;CINⅡ~Ⅲ级、宫颈浸润性鳞癌组织与正常宫颈组织阳性表达率比较,差异有统计学意义(P=0.011,P=0.006)。宫颈高级别上皮内瘤样病变和宫颈癌组织具有较高的HPV感染率,HPV感染与否和HMGA2的表达两者之间未发现统计学相关性。结论HMGA2高表达于高级别宫颈上皮内瘤样病变组织和宫颈癌组织,这可能是宫颈病变的一个早期事件。HMGA2的表达与宫颈HPV感染两者没有相关性,HMGA2可能是...     

环氧合酶-2、bcl-2蛋白在宫颈鳞癌组织中的表达及意义

目的:探讨宫颈鳞癌组织中环氧合酶(COX-2)、bcl-2蛋白的表达及其与宫颈癌临床分期、病理分级、淋巴转移的关系。方法:采用免疫组化法对40例宫颈癌组织中COX-2和bcl-2蛋白的表达进行检测分析,以10例正常宫颈组织作为对照。结果:COX-2和bcl-2蛋白在正常宫颈组织中阳性表达率均为0(0/10)。COX-2在宫颈原位癌、Ⅰ~Ⅱ期及Ⅲ期的阳性表达率分别为50.0%、54.5%和66.7%,宫颈鳞癌及正常宫颈组织组之间比较差异有显著性(P<0.05),宫颈原位癌、宫颈鳞癌Ⅰ、Ⅱ、Ⅲ期间差异无显著性(P>0.05)。COX-2在Ⅰ~Ⅱ期宫颈鳞癌表达与淋巴结转移有关(P<0.05)。bcl-2在宫颈原位癌、宫颈鳞癌Ⅰ~Ⅱ期、Ⅲ期癌细胞胞浆中未着色,但在癌间质有不同程度染色。bcl-2在宫颈癌及正常宫颈组织组之间差异有显著性(P<0.05)。宫颈原位癌、宫颈癌Ⅰ、Ⅱ、Ⅲ期间差异无显著性(P>0.05)。bcl-2与癌细胞分化程度及淋巴结转移无关(P>0.05)。COX-2与bcl-2在宫颈鳞癌组织中表达无相关性(P>0.05)。结论:COX-2和bcl-2蛋白在正常宫颈组织中均不表达。COX-2在宫颈鳞癌中的表达与临床分期和病理分级无关,与淋巴结转移有关。二者在宫颈癌中的表达无相关性。检测宫颈鳞癌组织中COX-2的表达有利于早期诊断及估计宫颈癌患者的预后。     

水通道蛋白1、8在不同宫颈上皮病变组织中的表达及其意义

目的探讨水通道蛋白1(AQP1)和水通道蛋白8(AQP8)在维吾尔族妇女宫颈癌发生、浸袭过程中的表达及意义。方法选择2008年11月至2010年8月新疆医科大学附属肿瘤医院维吾尔族宫颈炎患者42例、宫颈上皮内瘤变(CIN)Ⅲ36例,宫颈癌98例。采用实时荧光定量RT-PCR方法和Western blot对其中10例宫颈炎和27例宫颈癌进行AQP1和AQP8 mRNA和蛋白检测;采用免疫组化对全部宫颈癌患者98例、CINⅢ36例及宫颈炎42例AQP1微血管密度和AQP8阳性率进行分析。结果 AQP1和AQP8在宫颈炎、宫颈癌早期(Ⅰb或Ⅱa期)及晚期(Ⅲ期)均有表达。宫颈炎组和宫颈癌早期、晚期组AQP1和AQP8 mRNA表达差异无统计学意义(P>0.05),而蛋白表达差异有统计学意义(P<0.01)。AQP1微血管密度和AQP8阳性表达率在宫颈炎、CINⅢ和宫颈癌组织中比较差异有统计学意义(P<0.01)。结论 AQP1和AQP8在宫颈癌发生、侵袭过程中可能发挥重要的生理作用。     

SHP-2在宫颈病变组织中的表达及其与HPV感染的关系

目的研究SHP-2在宫颈病变组织中的表达及其与HPV感染的关系。方法选取2013年1月~12月在我院妇产科住院治疗的70例宫颈鳞癌患者(宫颈癌组)、50例宫颈上皮内肿瘤患者(CIN组)及20例宫颈正常患者(正常组),取宫颈组织,采用免疫组化染色检测宫颈组织中SHP-2的表达。结果宫颈癌组SHP-2的表达明显高于正常组,差异有统计学意义(P0.05);宫颈癌组SHP-2的表达明显高于CIN组,差异有统计学意义(P0.05);CIN组与正常组SHP-2表达水平比较,差异无统计学意义(P0.05);HPV16/18在正常组的感染率为15.0%,在CIN组的感染率为74.0%,在宫颈癌组的感染率为82.9%,差异有统计学意义(P0.05);采用Spearman相关分析,结果证实HPV感染和SHP-2在宫颈癌组织中的表达有相关性差异有统计学意义(r=0.331,P0.05)。结论 SHP-2在宫颈癌患者组织中高表达,HPV感染与宫颈癌发生有关,在宫颈癌组织中HPV感染与SHP-2的表达存在相关性。     

HPV16基因整合与FHIT蛋白缺失在宫颈癌变中的作用

目的 探讨HPV16的基因型整合状态及FHIT基因缺失在宫颈癌发生发展中的作用及相关性。方法选取44例宫颈癌、58例宫颈上皮内瘤样病变(CIN)和20例宫颈正常组织的患者,免疫组化检测宫颈FHIT蛋白的表达;并用多重PCR法检测HPV16 E2/E7表达。结果 122例单一HPV16阳性标本HPV16总整合率为78.69%,在正常宫颈组织、CIN1、CIN2、CIN3和宫颈癌中整合率分别为60.00%、66.67%、75.00%、86.96%和88.63%,随病变加重,整合率增强,组间差异有统计学意义(P0.05);FHIT蛋白的总缺失率为43.44%,FHIT蛋白在正常宫颈组织、CIN1、CIN2、CIN3和宫颈癌中的缺失率分别为15.00%、20.00%、25.00%、43.48%和72.73%。FHIT蛋白的缺失率,随病变加重,缺失率增高,组间差异有统计学意义(P0.05)。FHIT蛋白缺失在不同HPV16整合时不同,差异有统计学意义(P0.05)。结论 HPV16基因整合和FHIT蛋白缺失在宫颈癌的发生、发展中起重要作用,HPV16基因整合可能通过诱导FHIT基因低表达从而促使宫颈癌发生发展。     

FHIT基因、HPV16E6的表达与宫颈鳞癌发病的相关性研究

目的：探讨抑癌基因脆性组氨酸三联（fragile histine triad,FHIT）基因、人乳头瘤病毒16E6（HPV16E6）蛋白在宫颈鳞癌中的表达及其相互关系。方法：应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接（SP）法观察40例宫颈鳞癌、30例宫颈上皮内瘤样病变（CIN）和30例正常宫颈组织中FHIT基因、HPV16E6的表达。结果：FHIT基因在正常宫颈组织、CIN和宫颈鳞癌组织中的阳性表达率分别为96.7%,66.7%和30.0%,各组间阳性等级表达比较差异有统计学意义（χ2=43.595,P〈0.001）。FHIT基因阳性表达在宫颈鳞癌病理分级、临床分期中的比较,差异无统计学意义（χ2分别为3.378和3.315,均P〉0.05）。HPV16E6在正常宫颈组织、CIN和宫颈鳞癌组织中的阳性表达率分别为13.3%,53.3%和82.5%,各组间阳性等级表达比较差异有统计学意义（χ2=32.538,P〈0.001）。HPV16E6蛋白阳性表达在宫颈鳞癌病理分级、临床分期中的比较,差异无统计学意义（χ2分别为0.231和1.399,均P〉0.05）。结论：宫颈鳞癌中FHIT基因表达减少或缺失,以及HPV16E6的高检出率,提示二者在宫颈鳞癌的发生发展中起重要作用,可能是宫颈鳞癌发病机制之一。通过对FHIT基因和HPV16E6蛋白的致病机制以及相互影响的研究,有助于揭示宫颈癌发病机制,二者有可能用于临床宫颈癌诊断、预防和基因治疗。     

宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义

目的探讨宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义。方法选取2015年1月至2017年10月河北省承德医学院附属医院保存的宫颈癌组织58例,宫颈上皮内瘤变(CIN)组织47例,正常宫颈组织43例,采用免疫组化染色检测C-Fos、PDGFR蛋白阳性表达,western blot检测C-Fos、PDGFR蛋白表达量。结果宫颈癌组织C-Fos和PDGFR蛋白阳性表达率分别为58.62%和62.07%,C-Fos和PDGFR蛋白表达量分别为(0.987±0.221)和(0.872±0.206),明显高于CIN和正常宫颈组织(P 0.05);CIN组织C-Fos和PDGFR蛋白阳性表达率分别为21.28%和27.66%,C-Fos和PDGFR蛋白表达量分别为(0.344±0.157)和(0.550±0.214),明显高于正常宫颈组织(P 0.05);Ⅲ～Ⅳ期宫颈癌C-Fos和PDGFR蛋白表达量分别为(1.012±0.220)和(1.012±0.220),明显高于Ⅰ～Ⅱ期宫颈癌(P 0.05);中低分化宫颈癌PDGFR蛋白表达量为(0.892±0.184),明显高于高分化宫颈癌(P 0.05);宫颈癌组织C-Fos和PDGFR蛋白表达量无相关性(P0.05)。结论宫颈鳞癌组织C-Fos、PDGFR蛋白表达明显高于CIN和正常宫颈,与临床分期和分化程度具有一定的相关性,可能在宫颈癌发生过程中发挥一定的作用。     

宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义北大核心CSCD

目的探讨宫颈鳞癌组织C-Fos、PDGFR蛋白的表达及意义。方法选取2015年1月至2017年10月河北省承德医学院附属医院保存的宫颈癌组织58例,宫颈上皮内瘤变(CIN)组织47例,正常宫颈组织43例,采用免疫组化染色检测C-Fos、PDGFR蛋白阳性表达,western blot检测C-Fos、PDGFR蛋白表达量。结果宫颈癌组织C-Fos和PDGFR蛋白阳性表达率分别为58.62%和62.07%,C-Fos和PDGFR蛋白表达量分别为(0.987±0.221)和(0.872±0.206),明显高于CIN和正常宫颈组织(P <0.05);CIN组织C-Fos和PDGFR蛋白阳性表达率分别为21.28%和27.66%,C-Fos和PDGFR蛋白表达量分别为(0.344±0.157)和(0.550±0.214),明显高于正常宫颈组织(P <0.05);Ⅲ～Ⅳ期宫颈癌C-Fos和PDGFR蛋白表达量分别为(1.012±0.220)和(1.012±0.220),明显高于Ⅰ～Ⅱ期宫颈癌(P <0.05);中低分化宫颈癌PDGFR蛋白表达量为(0.892±0.184),明显高于高分化宫颈癌(P <0.05);宫颈癌组织C-Fos和PDGFR蛋白表达量无相关性(P>0.05)。结论宫颈鳞癌组织C-Fos、PDGFR蛋白表达明显高于CIN和正常宫颈,与临床分期和分化程度具有一定的相关性,可能在宫颈癌发生过程中发挥一定的作用。     

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。     

Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.     

宫颈鳞癌和上皮内瘤变组织中TRF1、TRF2及HPV16、HPV18的检测及其意义

目的研究端粒结合蛋白TRF1、TRF2在宫颈鳞癌发生发展中的作用并分析HPV16、HPV18感染与TRF1、TRF2蛋白表达的关系。方法随机选择南华大学附属第一医院病理科2005年9月至2006年10月期间的组织石蜡块标本共86例,采用原位杂交方法检测HPV16、HPV18在15例正常宫颈上皮、36例宫颈上皮内瘤变(CIN)和35例宫颈鳞癌组织中的感染情况;采用免疫组化方法检测所有组织标本中TRF1、TRF2蛋白的表达。结果(1)HPV16、HPV18阳性感染率CIN组[63.9%(23/36)]和宫颈鳞癌组[97.1%(34/35)]显著高于正常组[20.0%(3/15)](χ2=30.639,P<0.01)。(2)TRF1阳性表达率宫颈鳞癌组[40.0%(14/35)]显著低于CIN组[63.9%(23/36)]和正常组[86.7%(13/15)](χ2=10.237,P<0.01);CINⅢ组[42.9%(6/14)]显著低于CINⅠ组[90.0(9/10)](χ2=5.531,P<0.01)。TRF2阳性表达率宫颈鳞癌组[80.0%(28/35)]显著高于CIN组[52.8%(19/36)]和正常组[...     

Expression of matrix metalloproteinase-2 in preinvasive and invasive carcinoma of the uterine cervix

PURPOSE: To study the immunohistochemical expression of matrix metalloproteinase-2 (MMP-2) in preinvasive and invasive carcinoma of the uterine cervix so as to demonstrate whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: A total number of 50 samples of cervical tissue were studied for MMP-2 immunoreactivity. The cases were selected to include ten normal cases used as a control group, 20 CIN cases and 20 cervical carcinoma cases. The CIN group was subdivided into CIN1 (n = 7), CIN2 (n = 6) and CIN3 (n = 7), while the carcinoma group was represented by squamous cell carcinoma (n = 16) and adenocarcinoma (n = 4). RESULTS: MMP-2 expression was totally absent in control cervices and low-grade squamous intraepithelial lesions, while high-grade squamous intraepithelial neoplasia and invasive carcinoma showed up-regulation of MMP-2 expression with no significant difference concerning the type of carcinoma. This overexpression of MMP-2 points to the possibility that it is an early marker of tumor progression in cervical carcinoma. CONCLUSIONS: MMP-2 has a key role in extracellular matrix degradation and invasion in carcinoma of the uterine cervix. Its expression in high-grade squamous intraepithelial lesions may denote a potential risk for invasion and metastasis.     

AQP1和AQP3在子宫颈鳞状细胞癌中表达的研究

目的:探讨AQP1和AQP3在子宫颈癌中的表达及意义。方法:通过荧光定量PCR和免疫荧光检测AQP1和AQP3在人子宫颈癌SiHa细胞系中的表达,通过免疫组化检测AQP1和AQP3在35例维吾尔族子宫颈癌、15例CINⅢ和15例慢性宫颈炎中的表达。结果:(1)SiHa细胞中AQP1和AQP3在mRNA和蛋白水平均表达;(2)AQP1表达于宫颈病变组织间质血管内皮细胞的胞质,采用微血管密度(MVD)表示AQP1表达强度。慢性宫颈炎、CINⅢ和子宫颈癌组的MVD分别是43.6±17.8、56.2±11.6、70.8±21.1,宫颈癌组MVD显著高于CINⅢ组及慢性宫颈炎组(P均<0.05),CINⅢ和慢性宫颈炎组间差异无统计学意义;AQP3在慢性宫颈炎、CINⅢ和子宫颈癌组的阳性率分别是13.33%、26.67%、48.57%,子宫颈癌组与慢性宫颈炎组间差异有统计学意义(P=0.018),子宫颈癌组与CINⅢ、CINⅢ与慢性宫颈炎组间差异均无统计学意义(P均>0.05)。结论:AQP1和AQP3的表达可能与子宫颈癌的发生、发展有关。     

FHIT在宫颈癌及宫颈上皮内瘤变的表达及意义

目的:探讨在宫颈癌和宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)发生中脆性组氨酸三联体(fragile histid ine triad,FHIT)基因表达异常的作用及与HPV感染的关系。方法:用免疫组化法检测67例宫颈癌、42例CINⅢ和35例正常宫颈上皮组织的FHIT的表达。用PCR法检测宫颈癌石蜡组织中的HPV DNA,并用直接测序法或反向核酸杂交法对HPV分型。结果:正常宫颈组织中FHIT基因表达下调率为8.6%,CINⅢ组为28.57%,宫颈癌组为46.27%,差异均有统计学意义(P<0.05)。CINⅢ组FHIT蛋白表达下调率虽比宫颈癌组为低,但组间无统计学差异(P=0.66)。67例宫颈癌病例中,高危型HPV感染阳性者的FHIT表达下降或缺失占55.32%,明显高于无高危型HPV感染者(20%)(P<0.05)。宫颈癌患者的年龄、临床分期、肿瘤组织学分级、肿瘤浸润深度和淋巴结转移与FHIT蛋白表达均无明显相关(P>0.05)。FHIT表达下调或缺失31例宫颈癌患者的5年生存率为77.1%,FHIT正常表达36例的5年生存率为79.3%(P>0.05)。结论:FHIT在宫颈癌及CINⅢ中的表达明显下调,可能与HPV感染协同在宫颈癌的发生中起了重要作用。而FHIT在宫颈癌发展中的作用及与预后的关系,有待大样本的进一步研究。     

宫颈鳞癌和腺癌中微血管密度和基质金属蛋白酶-2 、9及其抑制剂-1、2表达的研究

目的通过观察肿瘤微血管密度(MVD)及MMP-2、MMP-9和TIMP-1、TIMP-2在宫颈鳞癌与腺癌组织中的表达情况,在蛋白水平探讨宫颈腺癌较鳞癌恶性程度高的可能原因.方法采用免疫组织化学方法(SP) 检测40例宫颈鳞癌和20例宫颈腺癌组织的MVD和MMP-2、MMP-9、TIMP-1、TIMP-2蛋白的表达情况.结果MVD在宫颈腺癌中较鳞癌高.MMP-2在宫颈鳞癌的阳性表达强度较腺癌高(P=0.006);MMP-9、TIMP-1在腺癌的阳性表达较鳞癌高(P=0.078,P=0.000);TIMP-2在两组间比差异无显著性(P＞0.05).在宫颈癌的临床病理特征中,MMP-2和MMP-9在鳞癌和腺癌中的表达不一,而TIMP-1始终是在腺癌中的表达较鳞癌高.结论宫颈腺癌较鳞癌恶性程度高的原因,可能与较高的MVD和TIMP-1的高表达有关.     

Immunohistochemical studies on epidermal growth factor receptor in oncogenesis of uterine cervical cancer

Recent studies have demonstrated that epidermal growth factor receptor (EGF-R) shows great homology with the v-erbB transforming protein and the amplified expression of EGF-R accompanies the malignant transformation of squamous epithelium of the uterine cervix. In this study, the tissue localization of EGF-R in the oncogenesis of uterine cervical cancer was examined by the avidin/biotin immunoperoxidase technique using anti-EGF-R monoclonal antibody. Normal squamous and columnar epithelium was almost negative for EGF-R. The positive rate of EGF-R increased in the precancerous lesions, whereas it decreased in invasive and metastatic cancer (mild dysplasia: 36%, moderate dysplasia: 57%, severe dysplasia: 77%, carcinoma in situ: 82%, microinvasive carcinoma: 80%, squamous cell carcinoma: 24%, glandular dysplasia: 67%, adenocarcinoma in situ: 75%, adenocarcinoma: 8%, adenosquamous carcinoma: 33%, metastatic carcinoma of the pelvic lymph node: 21%). The positive rate of dysplasia in follow up cases was high in the progressive group (regressive group: 0%, persistent group: 62%, progressive group: 80%). These results suggest that EGF-R may play an important role in the early stage of carcinogenesis of uterine cervical cancer, and it will be used as one of the markers in the prognosis of precancerous lesions of the uterine cervix.     

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.     

Human papillomavirus DNA in adenocarcinoma in situ, microinvasive adenocarcinoma of the uterine cervix, and coexisting cervical squamous intraepithelial neoplasia

Previously, human papillomavirus (HPV) DNA, mainly HPV-18 DNA, was detected in more than 40% (17/40 cases) of invasive adenocarcinoma of the uterine cervix in our laboratory. In order to identify HPV DNA in the precursor lesions of adenocarcinoma of the cervix, 11 cases of adenocarcinoma in situ containing microinvasive adenocarcinoma and 10 cases of adenocarcinoma in situ were studied for the presence of HPV DNA by in situ hybridization using highly sensitive 3H-labeled HPV-16 and HPV-18 DNA probes. HPV types present in cervical squamous intraepithelial neoplasia (CIN) coexisting with adenocarcinoma in situ and microinvasive adenocarcinoma were also studied. Apart from the coexisting CIN II-III with glandular neoplasms, 48 cases of CIN III (severe dysplasia and squamous carcinoma in situ) removed by conization or hysterectomy and known to be free of adenocarcinoma were used for comparison. HPV DNA was detected in 64% of microinvasive adenocarcinoma, 70% of adenocarcinoma in situ, and 63% of the control CIN III. HPV-18 DNA was the preponderant type of HPV DNA found in adenocarcinoma in situ and microinvasive adenocarcinoma. All cases of HPV DNA-positive microinvasive adenocarcinoma contained the same type of HPV DNA as the lesions of coexisting adenocarcinoma in situ. CIN coexisting with microinvasive adenocarcinoma or adenocarcinoma in situ contained the same type of HPV as identified in the glandular lesions, whereas all of the HPV DNA-positive control CIN III cases contained HPV-16 DNA. These results suggest that adenocarcinoma in situ is a precursor lesion of adenocarcinoma of the cervix that contains HPV DNA, and that CIN coexisting with adenocarcinoma may be a result of a metaplastic process of adenocarcinoma or of bidirectional differentiation of the affected reserve cells.