Bcl-2 expression in preinvasive and invasive cervical lesions

PURPOSE: To determine the correlation between bcl-2 expression and clinicopathological findings in cervical intraepithelial neoplasias (CIN I, II, III) and invasive cervical lesions, and its effect on overall survival rate. METHODS: Fifty specimens derived from 22 preinvasive and invasive cervical cancer cases up to surgical stage IIb (21 squamous cervical carcinoma and 7 adenocarcinoma cases) were preserved in paraffin blocks from primary surgery and constituted the study group. Tissues were processed and stained by immunohistochemical methods to assess the degree of bcl-2 expression. RESULTS: Positive bcl-2 expression was detected in 54% (13/21) of invasive lesions, while negative in 46% of cases. In CIN's, overall bcl-2 positivity was detected in 68% of cases. Bcl-2 expression was highly relevant between low grade (CIN I) and high grade (CIN II-III) lesions (p < 0.05). As regards degree of tissue staining for bcl-2 in CIN III cases, a statistically relevant difference was detected in comparison with low-grade preinvasive lesions (p < 0.05). In invasive cervical cancer cases, patients with bcl-2 positivity had a longer survival rate. By using the Cox regression model, univariate analysis did not show any specific prognostic factor to be important for survival rate, whereas, on multivariate analysis, histopathologic subtypes (p = 0.0390) and stage of tumor (p = 0.0451) had a statistically significant impact on overall survival rate. CONCLUSIONS: Bcl-2 expression, especially in preinvasive lesions, may play a role in the apoptotic process and be regarded as a marker for disease progression. In invasive cervical carcinomas, bcl-2 expression has not been shown to be effective in overall survival rates.     

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.     

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 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.     

MMP-1 and MMP-2 in the cervix uteri in different steps of malignant transformation--an immunohistochemical study.

OBJECTIVES: Enzymatic degradation of the extracellular matrix (ECM) represents a key element in the multistage process of tumor invasion and metastasis. This process requires extensive degradation of ECM components such as basement membrane collagen (type IV) and interstitial collagen (type I, II, III). Matrix metalloproteinase-2 (MMP-2) specifically cleaves collagen type IV, the major collagen of the basement membrane. MMP-1 digests interstitial collagen type I and III, the main collagen types of the stromal extracellular matrix. We investigated protein levels of MMP-1 and MMP-2 in different stages of malignant transformation. METHODS: Using the APAAP method we analyzed 10 normal cervical tissues, 11 cervical intraepithelial neoplasia 1 (CIN 1), 8 CIN 2 and 10 CIN 3 lesions, and 15 invasive squamous cell carcinomas. These data were compared with the HPV DNA status tested by hybrid capture II. RESULTS: Only a few isolated epithelial cells stained positively for MMP-1 and MMP-2 in normal cervical tissue and CIN 1 lesions. The CIN 2 and CIN 3 group displayed a heterogeneous distribution of MMP expression. 3 CIN 2 and 8 CIN 3 lesions showed strong MMP-2 and weak MMP-1 expression in the dysplastic epithelial cells. 5 CIN 2 and 2 CIN 3 lesions stained negatively. Invasive carcinomas showed a coexpression for MMP-1 and MMP-2 in malignant epithelial cells and peritumoral stroma cells. All MMP-2-positive cases tested positive for the HPV high-risk group. CONCLUSIONS: The expression of MMP-2 protein in preinvasive lesions of the cervix uteri and a consecutive coexpression of MMP-1 and MMP-2 in invasive cancer suggest a gradually increasing invasive potential. MMP-2 expression, when focally observed in high-grade squamous intraepithelial lesions of the cervix, may indicate tumor areas with an increased risk for invasive growth.     

Comparative study of MMP-2 (matrix metalloproteinase 2) immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma

OBJECTIVE: This study was undertaken to evaluate the levels of matrix metalloproteinase 2 (MMP-2) in the precursors lesions and in the invasive cervical carcinoma and to quantify the immune reactive expression of MMP-2, using MMP-2 immunohistochemistry, in intraepithelial cervical neoplasias and in the invading cervical carcinoma. STUDY DESIGN: We evaluated 60 samples of cervical tissues using immunohistochemistry for MMP-2 in 5 distinct groups. The groups were divided in control, cervical intraepithelial neoplasia I (CIN I), CIN II, CIN III, and cervical invading carcinoma. RESULTS: MMP-2 expression was found gradually increased according to the degree of cervical intraepithelial neoplasia and cervical carcinoma. (Control相似文献   

高危型人乳头状瘤病毒DNA检测与细胞学联合检查对子宫颈癌前病变筛查的研究

目的评价高危型人乳头状瘤病毒(HPV)DNA检测联合宫颈细胞学检查对宫颈癌前病变筛查的效果。方法2003年1月至2004年6月,对广东省人民医院妇科门诊5210名妇女进行宫颈癌前病变筛查,采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPV DNA联合细胞学检查,同时进行阴道镜检查,并以宫颈活检的组织病理学结果为确诊标准。结果受检者平均年龄(34±9)岁,筛查并最后经病理诊断为HPV感染890例,宫颈上皮内瘤变(CIN)Ⅰ级83例,CINⅡ73例,CINⅢ80例,宫颈浸润癌54例,子宫内膜癌5例,阴道上皮内瘤样病变1例,宫颈结核1例。以组织病理学为确诊标准,高危型HPV DNA检测CINⅡ、Ⅲ的敏感度是92·22%,特异度是74·71%,阳性预测值5·19%,阴性预测值99·84%。宫颈细胞学筛查CINⅡ、Ⅲ,以未明确诊断意义的不典型鳞状上皮细胞(ASCUS)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是90·00%、80·34%、11·94%和99·63%;以低度鳞状上皮内病变(LSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是70·13%、91·58%、11·11%和99·51%;以高度鳞状上皮内病变(HSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是48·05%、98·46%、31·90%和99·21%。高危型HPV DNA检测联合细胞学检查筛查CINⅡ、Ⅲ的敏感度、特异度、阳性预测值和阴性预测值分别是98·70%、73·08%、5·21%和100·00%。高危型HPV DNA在不同宫颈病变中的阳性率分别是:宫颈癌85·2%(46/54),CINⅢ92·5%(74/80),CINⅡ86·3%(63/73)和CINⅠ45·8%(38/83)。结论高危型HPV DNA检测在宫颈癌前病变的筛查中有很高的敏感度和阴性预测值,高危型HPV DNA检测联合细胞学检查可使敏感度和阴性预测值有提高,但特异度未能提高。     

子宫颈上皮癌变过程中Ki67表达和HPV感染的研究

目的 研究Ki67表达和HPV感染在宫颈癌发生发展过程中的意义。方法 分别从正常宫颈(10例)、各级CIN(CIN Ⅰ19例,CIN Ⅱ9例,CIN Ⅲ16例)和宫颈鳞癌(8例)的石蜡标本提取基因组DNA,选取HPV L1区通用引物进行PCR扩增,测序,与已知HPV序列进行同源性分析。Ki67免疫组化染色。结果 正常宫颈组HPV DNA均为阴性。CIN Ⅰ组5/19例为高危型HPV(16/18型),8/19例为中危型(35型等),其余为低危型。CINⅡ和Ⅲ组高危和中危型HPV各占一半。宫颈癌组均为高危型,绝大部分为HPV16。Ki67指数随CIN级别的升高(CINⅠ:21.4±1.1,CINⅡ:31.8±3.5 CINⅢ:61.3±2.8)而明显增加(P<0.01)。结论Ki67指数反映出在宫颈上皮细胞癌变过程中细胞增殖活性的改变。HPV型别与CIN级别及转归密切相关。Ki67与HPV检查联合应用对评价CIN细胞增殖活性及其转归有重要的作用,对伴有HPV16/18 感染的CIN应密切追踪和积极处理。     

Evaluation of adenoassociated virus 2 and human papilloma virus 16 and 18 infection in cervical cancer biopsies

OBJECTIVE: Protective roles of adenoassociated virus (AAV) 2 in cervical tumorigenesis are controversial. In an effort to clarify this issue, we tested prevalence of AAV 2 and human papillomavirus (HPV) infection in cervical lesions and adjacent normal tissues. METHODS: Tissues of cervical intraepithelial neoplasm (CIN) I (20 patients), CIN II (24 patients), CIN III (25 patients), and invasive cancer (23 patients) were investigated by microdissection and PCR using HPV-16-, HVP-18-, and AAV-2-specific primers. RESULTS: AAV 2 was detected in 11 out of 20 CIN I (55%), 21 out of 24 CIN II (84.5%), 13 out of 25 CIN III (52%), and 12 out of 23 invasive cancer cases (52.2%). However, HPV 16 was detected in none out of 20 CIN I, 2 out of 24 CIN II (8.3%), 6 out of 25 CIN III (24%), and 6 out of 23 invasive cancer cases (26.1%). HPV 18 was detected in 1 case in CIN II (4.2%) and 2 cases in CIN III (8%). In 92 perilesional normal tissues, AAV 2 was detected in 53 cases (57.6%), displaying 25% of CIN I, 83.3% of CIN II, 52% of CIN III, and 65.2% of invasive cancer. CONCLUSION:The differences in AAV 2 prevalence are not significant between CIN and normal tissues. However, differences in HPV 16 are significant in CIN III and invasive cancer, as compared to CIN I, CIN II, and normal, suggesting no significant correlation between AAV 2 and cervical cancer. Thus, these results support the notion that AAV 2 is not associated with cervical tumorigenesis.     

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.     

HSP70在子宫颈鳞癌中的表达及与P53、c-myc表达的关系

目的 :探讨热休克蛋白 70 (heatshockprotein 70 ,HSP70 )在宫颈鳞癌组织中的表达 ,以及它与抑癌基因p5 3、原癌基因c myc表达之间的关系。方法 :采用免疫组化SABC法检测正常宫颈上皮组织、癌前病变宫颈上皮组织和浸润性宫颈鳞癌组织中HSP70、P5 3蛋白、c myc蛋白的表达 ,并分析其相互关系。结果 :HSP70在正常宫颈上皮组织、癌前病变宫颈组织和浸润性宫颈鳞癌组织中的免疫组化记分呈递增趋势 ,两两相比差异有显著性。HSP70免疫组化记分随鳞癌组织分化程度降低而升高。浸润性宫颈鳞癌中P5 3蛋白阳性组和c myc蛋白阳性组HSP70组织化学记分分别高于P5 3阴性组和c myc阴性组。结论 :HSP70表达与宫颈鳞癌发生发展有关 ,且与较低分化程度有关。HSP70可能通过与P5 3蛋白和c myc蛋白之间某种相互作用参与宫颈鳞癌的发生发展     

Clinical significance of p27 and Skp2 protein expression in uterine cervical neoplasm.

The loss of p27 indicates a poor prognosis in various solid tumors, and a decrease in p27 level is the result of increased degradation by Skp2. We evaluated the relationship of p27 and Skp2 protein expression to various clinicopathologic factors in 332 cases of untreated uterine cervical neoplasm using tissue microarray method. After immunohistochemical staining, 313 and 300 tumor samples were retrieved for interpretation for p27 and Skp2, respectively. High p27 protein expression (nuclear staining in more than 30% of the tumor cells) was seen in 39.9% (125/313 cases), including 32 cervical intraepithelial neoplasia (CIN) III (55.2%), 58 microinvasive squamous cell carcinoma (SCC) (56.9%), 21 invasive SCC (17.1%), 11 adenocarcinoma (55.0%), and 3 cases of other tumors (30.0%). High Skp2 protein expression was noted in 28.3% (85/300 cases), including 14 cervical intraepithelial neoplasia III (25.0%), 18 microinvasive SCC (18.75%), 45 invasive SCC (37.8%), 6 adenocarcinoma (30.0%), and 2 cases of other tumors (22.2%). Low p27 protein expression was correlated with large tumor size (P < 0.005), depth of invasion in squamous lesion (P < 0.0005), high stage (P < 0.0005), and poor survival (P < 0.005). High Skp2 protein expression was correlated with large tumor size (P < 0.05), depth of invasion in squamous lesion (P < 0.05), and high stage (P < 0.005), but not with patient survival. There was no significant correlation between p27 and Skp2 protein expression. Only tumor stage had prognostic significance in the multivariate analysis (P = 0.041). Patients with low p27 protein expression had worse prognosis, indicating that p27 may participate in the progression of cervical squamous cell lesions.     

子宫颈上皮内瘤变筛查方法的综合评价

目的　对宫颈上皮内瘤变 (CIN)筛查方法即宫颈涂片自动检测系统 (papnetcytologycomputertechnology ,CCT)和新柏氏程控超薄细胞检测系统 (thinpreppaptest,TPT)两种细胞学检查方法进行综合评价。方法　对因细胞学检查异常而行阴道镜下多点活组织检查 (活检 )及病理检查的 374例患者的临床资料进行回顾性分析。结果　细胞学检查诊断为炎症者 9 1% ,低度鳞状上皮内瘤变(LSIL) 4 3 3% ,高度鳞状上皮内瘤变 (HSIL) 2 0 3% ,可疑癌 1 9% ;经阴道镜下多点活检及病理检查 ,诊断为炎症者增加到 5 3 5 % ,CINⅠ减少到 17 9% ,CINⅡ、CINⅢ、原位癌占 2 5 4 % ,可疑早期浸润癌和浸润癌增加到 3 2 %。 2 5 4 %的细胞学不能明确诊断意义的不典型鳞状上皮病变中 ,5 2 6 % (5 0 /95 )为炎症或未见异常 ,4 7 4 % (45 /95 )为CINⅠ以上的病变。 374例患者中 ,行CCT检查者 188例 ,TPT检查者 186例 ,两种细胞学检查结果分别与阴道镜检查结果相比 ,TPT的符合率显著高于CCT(P<0 0 1)。细胞学检查诊断为LSIL及以下病变的符合率 (79 7% )显著高于诊断为HSIL以及癌变者的符合率 (2 0 3% ) ,两者比较 ,差异有显著性 (P <0 0 1) ,而两种细胞学检查方法间无差别。人乳头状瘤病毒 (HPV)感染的发生率为 34 0 % ,阴道镜检查的     

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，?     

冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变患者的预后影响因素分析

目的探讨冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变（HSIL）患者的预后影响因素。方法回顾分析1999年1月至2004年1月间,卫生部北京医院妇产科266例冷刀锥切手术切缘阴性的HSIL患者的临床资料,分析影响预后的因素,并随访治疗结局。其中宫颈上皮内瘤变（CIN）II20例,CIN11246例（包括原位癌82例）;腺体累及者40例,无腺体累及者226例;257例检测高危型人乳头状瘤病毒（HPV）患者中,高危型HPV阳性244例,阴性13例。结果中位数随访时间46个月,总复发率为8．6％（23／266）,无浸润癌发生。CINⅡ患者中1例（5．0％,1／20）复发,CINⅢ患者（不包括原位癌）中9例（5．5％,9／164）复发,而82例原位癌中13例（15．8％,13／82）复发,原位癌与CINⅡ及CINⅢ（不包括原位癌）患者复发率比较,差异均有统计学意义（P〈0．05）。腺体累及者中7例（17．5％,7／40）复发,无腺体累及者中16例（6．0％,16／226）复发,两者比较,差异有统计学意义（P〈0．05）。高危型HPV阳性者中21例（8．6％,21／244）复发,而13例高危型HPV阴性者中无一例复发,两者比较,差异有统计学意义（P〈0．05）。结论冷刀锥切术切缘阴性的HSIL复发率低;病理分级高和腺体受累是影响疗效及预后的因素。     

Telomerase Activation in Cervical Neoplasia

Objective: To examine the critical point at which telomerase activation occurs in the course of cervical carcinogenesis.Methods: Telomeric repeat assay protocol was used to measure telomerase activity in cell samples obtained from 155 Japanese women with various cervical conditions: normal cytology (n = 62), cervical intraepithelial neoplasia (CIN) (n = 63), and invasive squamous cell carcinoma (n = 30).Results: Telomerase activity was detected in five (8%) women with normal cytology, in 26 (41%) patients with CIN (26% of patients with CIN I, 35% with CIN II, and 68% with CIN III), and in 29 (97%) patients with invasive carcinoma. Telomerase activation was significantly more frequent in CIN than in normal cervices (P < .001), and the positive rate in CIN III was significantly higher than that in CIN I (P < .01) and CIN II (P < .05). Furthermore, telomerase activation was significantly more frequent in invasive carcinoma than in CIN III (P < .01).Conclusion: Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates well with grade of cervical lesion.     

子宫颈癌组织中水通道蛋白8和bcl-2蛋白的表达及其相关性

目的 探讨水通道蛋白(AQP)8、bcl-2蛋白在宫颈癌组织中的表达及其相关性.方法 采用免疫组化Envision二步法检测AQP8和bcl-2蛋白在74例宫颈癌(其中鳞癌46例、腺癌28例)、34例宫颈上皮内瘤变(CIN)和15例正常宫颈组织中的表达情况,并分析两者的相关性.结果 AQP8和bcl-2蛋白主要在CIN异型细胞和宫颈癌细胞的细胞质内表达,AQP8蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为98%、61%、71%和53%,鳞癌高于腺癌、CIN和正常宫颈组织,差异有统计学意义(P＜0.01);腺癌与CIN、正常宫颈组织比较,CIN与正常宫颈组织比较,差异均无统计学意义(P＞0.05).bcl-2蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为74%、71%、53%和20%,鳞癌与腺癌组织比较,差异无统计学意义(P＞0.05);鳞癌、腺癌高于CIN、正常宫颈组织,CIN也高于正常宫颈组织,差异均有统计学意义(P＜0.01).AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关(rs=0.463,P=0.000).结论 AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关,AQP8蛋白表达上调可能与宫颈癌的发生、发展有一定的关系.     

Alterations in the expression of selected MHC antigens in premalignant lesions and squamous carcinomas of the uterine cervix

BACKGROUND: The objective of the study was to determine whether there is a correlation between expression of selected major histocompatibility complex (MHC) antigens and the presence of carcinoma and premalignant lesions of the cervix. We also attempted to determine whether there is a correlation between expression of the selected MHC antigens in each grade of cervical intraepithelial neoplasia (CIN) and invasive carcinoma of the cervix. METHODS: Quantitative comparative analysis of MHC class I and class II expression between specimens of the uterine cervix was carried out. For detecting human leukocyte antigen (HLA) class I molecules, two primary antibodies were used, recognizing either epitopes of all free heavy chain class I molecules or epitopes of the HLA-Bw4 antigen. HLA class II antigens were detected by antibodies reacting with the alpha-chain of the HLA-DR molecule. An indirect immunoperoxidase technique was carried out using paraffin-embedded sections. The following groups of sections were formed: squamous metaplasia, CIN of different grades, and invasive carcinoma. The specimens were taken from women in whom routine histopathologic diagnosis of cervical lesions had been performed. RESULTS: A significant decrease in the mean number of stained cells showing expression of MHC class I antigens (HC 10 and Bw4) was found in the invasive cancer group of specimens. A decrease in Bw4 expression was also found in the CIN III group. The highest expression of the HLA-DR antigens was detected in the metaplastic epithelium compared to the other groups. In the dysplastic epithelium the expression of the HLA-DR antigens was increased in the highest grade of dysplasia (CIN III). Upregulation of HLA-DR expression was detected in invasive cancer specimens. CONCLUSIONS: Alterations in MHC expression are found in premalignant lesions and squamous carcinomas of the uterine cervix. Quantitative assessment with the use of an image analysis system is valuable in helping to discriminate staining patterns of HLA expression. Further studies are indicated to evaluate the prognostic value of the expression of selected MHC antigens.     

Laminin-5 gamma 2 chain expression in cervical intraepithelial neoplasia and invasive cervical carcinoma

BACKGROUND. To analyze the expression of laminin-5 gamma 2 chain, a protein which plays a major role in keratinocyte migration, in cervical intraepithelial neoplasia (CIN), and invasive cervical carcinoma associated with high-risk oncogenic human papillomaviruses (HR-HPVs). MATERIAL AND METHODS. The expression of laminin-5 gamma 2 chain protein has been analyzed by immunohistochemistry in 17 cases of low-grade squamous intraepithelial lesions (LSIL-CIN1), 35 high-grade squamous intraepithelial lesions (HSIL-CIN2/3), 18 microinvasive or invasive carcinomas, and three metastatic lymph nodes. All these lesions have been proved to contain HR-HPVs and were also positive for p16 protein which classically is overexpressed at all stages of cervical neoplasia and dysplasia linked with HR-HPVs. 20 cases of normal cervix served as controls. RESULTS. The expression of laminin-5 gamma 2 chain protein was observed in 100% of invasive or microinvasive carcinoma and in their related lymph node metastasis with an immunoreactivity located preferentially at the invasive front of the lesions. All the HSILs (100%) associated with invasive carcinoma were also positive. In contrast, in HSILs without associated invasive component, the expression of the protein has been found in only 34% of cases. In positive HSILs, laminin-5 gamma 2 protein was expressed in basal layers. In LSILs and normal epithelium, no expression of the protein was noted. CONCLUSIONS. We conclude the following: (i) the expression of laminin-5 gamma 2 is a late event in cervical carcinogenesis increasing with the grade of dysplastic lesions; (ii) laminin-5 gamma 2 expression facilitates the identification of invasive and microinvasive lesions which could be difficult to diagnose on the basis of routine stains; (iii) laminin-5 gamma 2 expression in HSILs could potentially identify those lesions with a more increased risk of tumor progression.