外阴病变组织中精子相关抗原-9的表达及意义

目的:研究外阴鳞状上皮内瘤变(VIN)和外阴鳞状细胞癌组织中精子相关抗原-9(SPAG9)的表达及其潜在的临床意义。方法:应用免疫组织化学技术检测16例VIN、41例侵袭性外阴鳞状细胞癌和10例正常外阴皮肤组织中SPAG9蛋白的表达。结果:SPAG9蛋白在VIN及侵袭性外阴鳞状细胞癌中的表达率均为100%,在正常外阴皮肤中表达率为0;根据H-score分值比较:SPAG9蛋白在外阴鳞状细胞癌组织中的表达高于VIN组织,G2～G3肿瘤组织中SPAG9蛋白表达高于G1者,有淋巴结转移者肿瘤组织内SPAG9蛋白的表达高于无淋巴结转移者,差异均有统计学意义(P<0.05);外阴鳞状细胞癌Ⅱ～Ⅲ期患者肿瘤组织中SPAG9蛋白的表达高于Ⅰ期,差异无统计学意义(P>0.05)。结论:SPAG9蛋白可能在外阴癌的发生和发展发挥重要作用,有望成为外阴癌早期诊断和预后评估的生物学标记物。     

果蝇zeste基因增强子蛋白在宫颈鳞状细胞癌中的表达及意义

目的 研究EZH2蛋白在宫颈鳞状细胞癌中的表达及其与宫颈癌临床病理参数之间的关系.方法 用SP免疫组织化学染色的方法检测正常宫颈组织30例,宫颈上皮内瘤变78例和宫颈鳞状细胞癌78例组织中EZH2的表达.结果 EZH2蛋白在正常宫颈组织、宫颈上皮内瘤变、宫颈鳞癌中表达率依次增强,分别为0、48、7%、78.2%.鳞状细...     

联合检测COX-2及bFGF在卵巢上皮性癌中的表达和意义

目的:探讨环氧化酶-2(COX-2)及碱性成纤维细胞生长因子(bFGF)在卵巢上皮性癌中的表达及意义.方法:采用免疫组化方法检测19例正常卵巢组织及50例卵巢上皮性癌中COX-2与bFGF的表达情况.结果:COX-2及bFGF在卵巢上皮性癌中的表达率分别为76%和78%,明显高于正常卵巢组织,两者在不同病理类型的卵巢上皮性癌中表达均无统计学差异,但在肿瘤的不同FIGO分期及分级中表达有统计学差异.COX-2与bFGF在卵巢上皮性癌中的表达有一致性.结论:COX-2及bFGF与卵巢上皮性癌的分化程度密切相关,检测COX-2及bFGF可作为判断卵巢上皮性癌恶性程度的生物学指标.     

宫颈鳞状上皮细胞癌组织中钙激活性中电导钾离子通道蛋白产物表达分析

目的探讨正常宫颈和宫颈癌组织中钙激活性中电导钾离子通道(IKCa1)与人类宫颈鳞状上皮细胞癌的相关性。方法取2007年10月至2008年4月泸州医学院附属医院手术治疗的30例不同分化程度的宫颈鳞状上皮细胞癌患者病变部位组织作为实验组,同时期18例正常宫颈上皮组织作为对照组,分别采用免疫组织化学方法检测上述组织中IKCa1蛋白产物表达部位及表达水平。结果 IKCa1在30例宫颈鳞状上皮细胞癌组织细胞核及细胞膜上均呈阳性表达,阳性表达率为100.0%;18例正常宫颈上皮组织中仅1例在鳞状上皮部位细胞膜部位有较弱表达,阳性表达率为5.6%,IKCa1蛋白产物在宫颈鳞状上皮细胞癌组织中的表达程度及表达部位均与正常宫颈组织中存在明显差异(Z=-6.109,P=0.00,P<0.05)。在不同分化程度的宫颈鳞状上皮细胞癌组织中,高分化鳞癌组阳性表达率为40.0%,中分化鳞癌组阳性率为90.0%,低分化鳞癌组阳性率为100.0%;IK-Ca1蛋白产物表达程度与癌细胞分化程度呈负相关(χ2=8.4,P<0.05)。结论宫颈鳞状上皮细胞癌组织中IK-Ca1蛋白产物的表达明显高于正常宫颈组织;且IKCa1蛋白产物表达水平与癌细胞的分化程度呈负相关;过高表达的IKCa1与宫颈鳞状上皮细胞癌的发生和发展可能存在重要联系。     

宫颈鳞癌中Cyclin E的表达和HPV16感染的相关研究

目的探讨Cyclin E在宫颈鳞状细胞癌中的表达及其与HPV16感染的关系.方法应用免疫组化S-P法对34例宫颈鳞状细胞癌组织进行Cyclin E与HPV16的检测,并与宫颈不典型增生和正常宫颈组织进行比较.结果正常宫颈组织无Cyclin E表达,宫颈不典型增生组织仅有少量袁达(11.11%),宫颈鳞状细胞癌有58.52%表达(P＜0.001),且与HPV16感染有明显相关性(P＜0.05).结论高危HPV感染是宫颈癌的重要病因,HPV感染通过多种途径改变了细胞的周期性调控,诱发细胞周期GI-S期检测点异常,引起细胞恶性增生,HPV感染与Cyclin E异常表达在宫颈癌的发生发展中起重要作用.     

CARM1、p16INK4a在子宫颈鳞状细胞癌中的表达及临床意义

目的检测子宫颈鳞状细胞癌(CSCC)、宫颈上皮内病变及正常宫颈组织中组蛋白精氨酸甲基转移酶1(CARM1)、p16INK4a的表达,探讨两者在子宫颈鳞癌发生发展中的作用。方法运用免疫组化技术检测CSCC、宫颈上皮内病变及正常宫颈组织中CARM1、p16INK4a表达,分析二者表达与子宫颈鳞状细胞癌临床病理特征及生存预后的关系,并评价两者的相关性。结果CARM1、p16INK4a蛋白阳性表达率在正常子宫颈组织、低级别鳞状上皮内病变(LSIL)、高级别鳞状上皮内病变(HSIL)、CSCC中呈递增趋势;子宫颈鳞状细胞癌组织CARM1蛋白阳性表达率为70.24%,与组织分化程度和浸润深度相关;p16INK4a蛋白阳性表达率为92.86%,表达与组织分化程度相关;单因素分析显示CARM1表达与OS相关,多因素分析显示仅FIGO分期是OS独立预后因素;CARM1和p16INK4a表达相关系数Rs=0.325,呈弱正相关关系。结论CARM1、p16INK4a可能参与了子宫颈鳞癌发生发展进程,是子宫颈鳞状细胞癌的不良预后因子,两者可能存在部分协同作用。     

黏蛋白-1在子宫颈癌中的表达及其临床意义

目的研究黏蛋白(mucins,MUC1)-1与宫颈鳞状细胞癌的发生发展及临床意义。方法选取宫颈鳞状细胞癌标本80例(研究组)和慢性宫颈炎标本20例(对照组),采用免疫组织化学、Western blot技术及QRT-PCR技术检测两组标本中MUC-1的表达。结果研究组中MUC-1的表达程度相比对照组明显增高(P0.05),而且在宫颈管壁浸润深度3 mm的癌组织中的表达较浸润深度≤3mm的表达增强(P0.05);但与宫颈癌患者年龄、组织分化程度、癌组织的浸润范围、是否淋巴结转移无关(P均0.05)。结论 MUC-1蛋白的表达可能与子宫颈鳞状细胞癌的发生和发展有关。     

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。     

人抗原RmRNA与蛋白和环氧合酶-2蛋白在卵巢浆液性肿瘤组织中的表达及其意义

目的 探讨人抗原R（human antigen R,HuR）mRNA与蛋白和环氧合酶-2（COX-2）蛋白在卵巢浆液性肿瘤组织中的表达及其与卵巢浆液性癌临床病理生物学特征的关系。方法 采用RT-PCR技术、免疫组化方法分别检测中国医科大学附属盛京医院2006年1月至2008年2月收集的31例卵巢浆液性癌组织标本、22例卵巢浆液性良性瘤组织标本中HuR mRNA与蛋白和COX-2蛋白的表达,并以8例正常卵巢组织作为对照组。结果 （1）HuR mRNA在卵巢浆液性癌中表达明显高于卵巢浆液性良性瘤和正常卵巢组织（P<0.05）。HuR mRNA 的表达与卵巢浆液性癌细胞分化有关（P<0.05）,与手术病理分期、淋巴结转移无关（P>0.05）。（2）HuR蛋白相对含量和胞浆表达阳性率在卵巢浆液性癌中的表达显著高于卵巢浆液性良性瘤和正常卵巢组织（P<0.05）。HuR蛋白相对含量和胞浆表达阳性率与卵巢浆液性癌细胞分化有关（P<0.05）,与手术病理分期、淋巴结转移无关（P>0.05）。（3）COX-2蛋白相对含量与卵巢浆液性癌手术病理分期有关（P<0.05）,与细胞分化、淋巴结转移无关（P>0.05）。依据31例卵巢浆液性癌中免疫组化结果半定量分析,经Spearman等级相关分析发现HuR与COX-2之间呈正相关（r=0.680,P=0.000）。结论 卵巢浆液性肿瘤的发展与胞浆中HuR的过表达有一定相关性,HuR与COX-2蛋白在卵巢浆液性癌中的表达呈正相关。     

外阴硬化性苔藓外阴上皮局部免疫状态初探

目的:探索外阴硬化性苔藓、外阴鳞状细胞癌上皮局部免疫状态。方法:选取2015年8月～2017年10月正常外阴患者15例、外阴硬化性苔藓患者30例和外阴鳞状细胞癌患者5例,免疫组化法检测外阴鳞状上皮免疫因子IFN-γ、IL-4、IL-17、HD-5、IgG的表达情况,透射电镜观察超微结构特点。结果:正常外阴组织、外阴硬化性苔藓、外阴癌鳞状上皮均不同程度表达IFN-γ、IL-4、IL-17、HD-5及IgG。外阴硬化性苔藓鳞状上皮IFN-γ、IgG免疫组化染色较正常外阴更深。与正常外阴鳞状上皮相比,外阴硬化性苔藓、外阴癌鳞状上皮IFN-γ、IL-4、IL-17、HD-5及IgG表达无显著差异。与外阴硬化性苔藓相比,外阴癌鳞状上皮上皮源性IgG表达显著下降。电镜下可见外阴硬化性苔藓鳞状上皮载色素细胞的减少。外阴鳞状细胞癌鳞状上皮可见细胞间桥减少,桥粒增多;细胞浆中张力源纤维减少;核仁中可见核小体等。结论:外阴硬化性苔藓发病可能与Th1类细胞因子IFN-γ、上皮源性IgG表达升高相关,与IL-4、IL-17及HD-5无显著相关性。     

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.     

子宫内膜癌组织中环氧化酶-2增强表达的临床意义

目的:探讨环氧化酶2(COX2)在子宫内膜癌组织中的表达,COX2与雌激素受体(ER)表达的关系及COX2在子宫内膜癌发生发展中的意义。方法:应用RTPCR技术检测30例子宫内膜癌、相应癌旁正常内膜腺体及15例子宫良性肿瘤中COX2mRNA的表达。应用免疫组化方法测定30例内膜癌中ER表达情况。结果:COX2mRNA在30例子宫内膜癌组织中有28例表达水平明显增高,癌组织与正常内膜腺体或良性肿瘤间COX2的表达差异有显著性意义(P<0.05)。ER阳性组与ER阴性组的COX2表达差异有非常显著性意义(P<0.01)。结论:子宫内膜癌组织中COX2mRNA表达水平高于正常内膜腺体或子宫良性肿瘤,激素依赖型子宫内膜癌中COX2表达高于非激素依赖型内膜癌且其表达在子宫内膜癌的发生、发展中具有重要意义。     

Expression of cyclooxygenase-2 (COX-2) and Ki67 as related to disease severity and HPV detection in squamous lesions of the cervix

OBJECTIVES: To assess the expression of cyclooxygenase (COX-2) and Ki67 in cervical squamous lesions in relation to disease severity and human papillomavirus (HPV) detection. SUBJECTS AND METHODS: For this cross-sectional study, 223 women subjected to diathermic conization of the cervix have been enrolled, between February 2001 and April 2004. All patients undertook pelvic examination, including colposcopy and collection of samples for Hybrid Capture II (HCII). Pathological assessment disclosed: 9 cases of normal epithelium/cervicitis, 33 CIN1, 28 CIN2, 146 CIN3 and 7 invasive squamous cell carcinomas. COX-2 and Ki67 protein expression was determined with immunohistochemistry. COX-2 immunoreactivity grading was based on the German ImmonoReactive score. The continuum percentage of positive cells was used for the assessment of nuclear Ki67 expression. RESULTS: Expression of COX-2 did not correlate with disease severity and with Ki67 expression. The HPV detection rates did not differ significantly across COX-2 protein expression strata, ranging from negative to strong expression. Ki67 expression, however, was higher in the CIN3 group (P = 0.001) as compared to the specimens rendered as normal/cervicitis. CONCLUSIONS: COX-2 protein expression did not correlate with disease severity or Ki67 expression.     

Prevalence and prognostic significance of COX-2 expression in stage IB cervical cancer

OBJECTIVES: To evaluate the prevalence of cyclooxygenase-2 (COX-2), correlation with various clinicopathologic factors and prognostic significance of COX-2 in stage IB cervical cancer patients. METHODS: 89 paraffin-embedded specimens of patients with stage IB cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy at King Chulalongkorn Memorial Hospital during 1 January 1997-31 December 2002 and were stained with polyclonal goat antiserum against COX-2 using immunohistochemical method. Medical records were reviewed; clinicopathological variables were retrieved and used for analysis. RESULTS: The prevalence of positive COX-2 expression in stage IB cervical cancer in this study was 49.4%. Positive COX-2 expression in cervical adenocarcinoma was higher than squamous cell carcinoma (86.7% versus 40.6%, P < 0.05) and significantly expressed when lymph node metastasis was presented (100% versus 46.4%, P < 0.05). However, COX-2 expression was possibly associated with parametrial involvement (80% versus 47.6%, P > 0.05). There was no correlation between COX-2 expression and patient's age, tumor size, depth of stromal invasion and lymphovascular space invasion. Five-year disease free survival and 5-year overall survival in patients with positive COX-2 expression were 81% and 98% which were not differed from patients with negative COX-2 expression (92% and 95%, P > 0.05). CONCLUSIONS: Strong correlation was found in cervical adenocarcinoma and lymph node metastasis. However, COX-2 expression failed to demonstrate as a significant prognostic factor in stage IB cervical cancer.     

Cyclooxygenase-2 and c-erbB-2 expression in uterine cervical neoplasm assessed using tissue microarrays

OBJECTIVES: Cyclooxygenase-2 (COX-2) and c-erbB-2 are involved in the pathogenesis of solid organ tumors. Chemotherapeutic agents targeting COX-2 and c-erbB-2 are used to treat colon and breast cancers. This study evaluated the significance and relationship of COX-2 and c-erbB-2 protein expression in untreated uterine cervical neoplasm. METHODS: This study included 332 patients with uterine cervical neoplasm. We constructed tissue microarray blocks that included two cores from each donor tumor and immunostained them with primary anti-cyclooxygenase-2 and anti-c-erbB-2 monoclonal antibodies. The clinical features and survival data were compared. RESULTS: Three hundred and eighteen tumor samples (95.8%) could be interpreted after immunohistochemical staining. COX-2 protein expression was noted in 140 cases of uterine cervical neoplasm (44.0%): In 26.7% of the cervical intraepithelial neoplasia III (16/60 cases), 37.9% of the microinvasive squamous cell carcinoma (39/103 cases), 51.6% of the invasive squamous cell carcinoma (64/124 cases), and 76.2% of the adenocarcinomas (16/21 cases) (P < 0.005). By contrast, except for one case of adenoid cystic carcinoma, none of the uterine cervical neoplasm expressed c-erbB-2 protein. COX-2 protein expression correlated with histology (P < 0.005) and stage (P < 0.05), but was not associated with patient survival. CONCLUSION: COX-2 may participate in the progression of cervical squamous cell lesions, while the contribution of c-erbB-2 to cervical carcinogenesis is probably small.     

Cyclooxygenase-2 and epidermal growth factor receptor expressions in different histological subtypes of cervical carcinomas.

This study was designed to evaluate the significance of cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) expression in a series of cervical adenocarcinoma (AC), cervical adenosquamous carcinoma (ASC), and cervical squamous cell carcinoma (SCC). One hundred thirty cases of cervical carcinoma (30 ASC, 50 AC, and 50 SCC) were analyzed for COX-2 and EGFR expressions using specific primary antibodies. Samples were scored semiquantitatively as follows: (-), 0% of immunoreactive cells; (+), <5% of immunoreactive cells; (++), 5% to 50% of immunoreactive cells; and (+++), >50% of immunoreactive cells. The COX-2 expression was more frequently positive than EGFR in all cervical cancers studied. The COX-2 expression was also more prominent in AC than in ASC (P = 0.003). Expression of either COX-2 or EGFR was significantly different when comparing SCC with AC (P < 0.001 and P = 0.04, respectively). There was no significant correlation between COX-2 and EGFR expressions and age at diagnosis, recurrence, distant metastasis, and/or positive status of regional lymph nodes, neither between COX-2 and EGFR coexpression and the clinical data analyzed. Nevertheless, our data support that there are significant differences between EGFR and COX-2 expressions in the 3 different histogenetic types of cervical cancer. Also, in terms of therapeutic strategies, our data can be valuable in the selection of patients eligible to receive specific EGFR/COX-2-targeted therapy.     

High cyclooxygenase-2 expression in cervical adenocarcinomas

OBJECTIVE: The purpose of this study was to examine the relationships between cyclooxygenase-2 (COX-2) expression and prognostic factors in cervical carcinomas. METHODS: We studied COX-2 expression in 53 women with cervical cancers, including 35 squamous cell carcinomas (SCCs), 1 adenosquamous cell carcinoma (ASCC), and 17 adenocarcinomas (ACs), using commercially available polyclonal antibodies on Formalin-fixed, paraffin-embedded tissues. Normal cervical tissues were obtained as from other patients with uterine myomas treated with a total hysterectomy (n = 16). The immunoreactivity was quantified using an immunohistochemical scoring system that approximates the use of an image analysis-based system. RESULTS: Twenty-two cervical cancer tissues (41.5%), including 10 SCCs and 12 ACs, expressed COX-2 at a moderate to strong level, which significantly, differed from the negligible expression found in the control group of 16 normal cervical tissues (P = 0.001). Different cell types showed significantly different expression levels of COX-2 (SCC at 28.6% vs AC at 70.6%, P = 0.004). The presence of deep stromal invasion (n = 40) showed a significant inverse relationship to COX-2 expression (32.5% vs 69.2%, P = 0.02). The expression of COX-2 in well-differentiated carcinomas was significantly increased compared to that in moderately and poorly differentiated carcinomas (72.7% vs 33.3%, respectively, P = 0.018). CONCLUSIONS: Overexpression of COX-2 was found in both SCC and AC, but SCCs showed infrequent and low expression. These findings suggest that increased COX-2 expression may play an important role in cervical adenocarcinomas.     

宫颈鳞状细胞癌组织细胞凋亡调控机制的研究

目的：通过对Fas、FasL和caspase的蛋白表达及与细胞凋亡关系的观察,探讨宫颈鳞状细胞癌组织中细胞凋亡的机制。方法：应用原位末端标记法（TUNEL）、双重荧光染色法等检测5例正常宫颈组织和34例不同分化程度的宫颈鳞状细胞癌组织的细胞凋亡和Fas、FasL、caspase－3、caspase－8蛋白的表达。结果：宫颈正常及鳞癌组织上有细胞凋亡及Fas、FasL、caspase－3蛋白的表达,各指标之间有相关性。癌组织中,Fas、FasL、caspase－3蛋白阳性细胞明显增多,双重荧光染色显示,部分细胞Fas及cspase－3蛋白与凋亡细胞同时阳性染色。宫颈正常及癌组织中无caspase－8蛋白表达。结论：正常宫颈及宫颈鳞癌组织中,细胞凋亡处于动态调整过程中,Fas／FasL可能通过活化caspase－3参与细胞凋亡的调节。