Human Papillomavirus Genotypes and Methylation of CADM1, PAX1, MAL and ADCYAP1 Genes in Epithelial Ovarian Cancer Patients

Background: High-risk types of human papillomavirus (HR-HPV) may play a role in the development of epithelial ovarian cancer (EOC). The aim of this study was to determine any HPV genotypes and correlations to CADM1, PAX1, MAL and ADCYAP1 gene methylation in Egyptian EOC patients. Materials and methods: The prevalence of HR-HPV in 100 formalin fixed paraffin embedded EOC tissues was determined using nested polymerase chain reaction (PCR) with MY09/MY11 and GP5+/GP6 + primers to amplify a broad spectrum of HPV genotypes in a single reaction. DNA sequencing was applied to identify HPV genotypes for the positive samples. All samples negative for HPV were re-analyzed for HR-HPV and low-risk HPV subtypes using type specific primers. Results: The prevalence of HPV was 10% in our EOC cases. HPV-16 and HPV-18 were the predominant genotypes followed by HPV−33, all being associated with advanced stages. Other HR-HPV and low risk HPV genotypes were not found. CADM1 was hypermethylated in 100% of patients infected with HPV-16 and HPV-33 and in 75% of patients infected with HPV-18. Hypermethylation of PAX1 was evident in 80% and in 75% of patients infected with HPV-16 and HPV-18 while MAL was hypermethylated in 100% and ADCYAP1 was hypermethylated in 60% and in 75%, respectively. Conclusion: The presence of high risk HPV genotypes among epithelial ovarian carcinoma may reflect an importance of infection in the pathogenesis of EOC. In HR-HPV infected cancers, DNA methylation may be one of the mechanisms triggering the alteration in CADM1, PAX1, MAL and ADCYAP1 gene expression levels.     

上皮性卵巢癌hTERT表达及端粒酶活性的研究

目的探讨人端粒酶反转录酶(hTERT)表达及端粒酶活性与卵巢癌发生、发展的关系,评价其可否作为卵巢癌的肿瘤标志物及预后指标.方法应用RT-PCR及端粒重复扩增方法对43例上皮性卵巢癌、11例良性卵巢肿瘤和卵巢正常组织以及4例交界性卵巢肿瘤共69份标本进行hTERTmRNA及端粒酶活性检测.结果hTERT表达及端粒酶活性率在卵巢癌中分别为83.7%(36/43)及76.7%(33/43),良性肿瘤中均为9%(1/11),在正常卵巢组织和交界性卵巢肿瘤中阴性,其差异在卵巢癌与良性肿瘤及正常组织间均有显著性(P值分别为0.0004及0.0001).hTERT及端粒酶阳性率在某些预后因素如肿瘤类型、组织学分级、临床分期及肿瘤转移之间的差异皆无显著性.结论卵巢癌中存在高频率的hTERT表达及端粒酶激活,表明hTERT作为端粒酶的催化亚基,在肿瘤细胞端粒酶的激活中起关键作用.hTERT表达及端粒酶活性可望作为有价值的肿瘤标志物而用于卵巢癌的早期诊断,但其预后价值尚有待于进一步研究.     

Diagnostic Performance of HPV E6/E7 mRNA and HPV DNA Assays for the Detection and Screening of Oncogenic Human Papillomavirus Infection among Woman with Cervical Lesions in China

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HRHPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with highgrade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.     

Lack of HPV in Benign and Malignant Epithelial Ovarian Tumors in Iran

Background: Ovarian epithelial tumors one of the most common gynecological neoplasms; we here evaluated the presence of HPV in benign and malignant examples. Methods: In this cross-sectional study the records of 105 patients with epithelial ovarian tumors (benign and malignant) referred to Imam Hossein University Hospital from 2012 to 2015 were evaluated along with assessment of the presence of the HPV infection using PCR. Results: Among 105 patients, comprising 26 (24.8%) with malignant and 79 (75.2%) with benign lesions, the factors found to impact on malignancy were age at diagnosis, age at first pregnancy, number of pregnancies and hormonal status. However, malignancies was not related to abortion, late menopause, and early menarche. In none of the ovarian tissues (benign and malignant) was HPV DNA found. Conclusion: In this study HPV DNA could not be found in any epithelial ovarian tumors (benign and malignant) removed from 105 women; more studies with larger sample size are needed for a definite conclusion.     

卵巢上皮性癌组织中长链非编码RNA PURPL的表达及其意义

  目的  检测长链非编码RNA PURPL（p53 upregulated regulator of p53 levels）在卵巢上皮性癌（epithelial ovarian cancer,EOC）组织中的表达情况,探讨其在卵巢癌发生发展中的作用。  方法  选用开放医学数据库lncRNASNP2、GEPIA和Kaplan-Meier Plotter检索PURPL在EOC组织中的表达及其与预后的关系。收集2012年10月至2015年10月郑州大学第一附属医院105例患者的临床病理资料,其中包括正常卵巢组织20例、良性卵巢上皮性肿瘤组织20例、EOC组织65例,采用实时荧光定量PCR检测上述不同卵巢组织中的PURPL表达情况,分析EOC组织中PURPL表达与EOC临床病理指标的关系,Kaplan-Meier法分析PURPL表达对EOC患者生存的影响。  结果  数据库检索显示,EOC组织中PURPL的表达显著高于正常卵巢组织,PURPL表达升高与EOC患者的总生存（overall survival,OS）率和无复发生存期（recurrence-free survival,RFS）缩短相关。实时荧光定量PCR检测显示,晚期EOC组织中的PURPL表达为0.530±0.004,显著高于正常卵巢组织的0.029±0.001、良性卵巢上皮性肿瘤组织的0.135±0.001和早期EOC组织的0.488±0.006的表达（P<0.0001）。临床分期越晚（χ2=10.785,P=0.001）、有淋巴结转移（χ2=4.481,P=0.034）的EOC组织中的PURPL高表达。PURPL表达水平相对较高的EOC患者的OS和RFS,明显短于PURPL表达水平相对较低的患者（P<0.05）。  结论  PURPL高表达提示EOC患者预后不良,可作为EOC预后监测的潜在标记物。      

Double HPV infection in African cervical cancer detected by polymerase chain reaction

Biopsy samples from 13 Kenyan patients with squamous cell carcinoma of the cervix were analysed for the presence of type specific HPV DNA by polymerase chain reaction (PCR). HPV 16 was confirmed in 11 (85%) and HPV 18 in 9 (69%) samples. HPV 6 DNA was detectable in only 3 (23%) samples and no HPV 33 was found. Infection with either HpV16 or 18 was seen in 12 (92%) and infection with both in 8 (62%) cases. The prevalence of double infection found is higher than in previous reports. The significance of this and possible effects of parity on cervical neoplastic changes are discussed.     

卵巢上皮性癌组织中DAPK基因启动子甲基化及其蛋白表达的研究

  目的  研究卵巢上皮性癌组织中DAPK基因启动子甲基化及其蛋白表达在卵巢癌发生发展过程中的作用及意义。  方法  应用甲基化特异性PCR(MSP)检测55例卵巢上皮性癌(恶性组)、25例卵巢交界性上皮性肿瘤(交界组)、30例卵巢良性上皮性肿瘤(良性组)、25例正常卵巢上皮组织(正常组)的石蜡包埋组织中DAPK基因启动子的甲基化情况。应用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接(S-P)法检测上述蜡块组织中DAPK蛋白的表达情况。  结果  DAPK启动子在正常组、良性组、交界组、恶性组的甲基化率分别为0(0/25)、6.7%(2/30)、16.0%(4/25)、47.3%(26/55), 差异有统计学意义(P < 0.001), 恶性组的甲基化率高于其他三组; DAPK蛋白在正常组、良性组、交界组、恶性组的阳性表达率分别为96.0%(24/25)、90.0%(27/30)、48.0%(12/25)、30.9%(17/55), 差异有统计学意义(P < 0.001), 恶性组、交界组的阳性表达率均低于正常组和良性组; DAPK基因启动子甲基化和DAPK蛋白表达呈负相关。  结论  DAPK基因启动子甲基化导致基因沉默、失活, 引起蛋白表达下调或缺失, 并参与了卵巢上皮性癌的发生发展。      

Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer

Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated bypromoter hypermethylation in many cancers. The current study was performed to evaluate the methylationstatus of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expressionand clinicopathologic characteristics. Method: We detected methylation of the RASSF2A gene in tissues andcorresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 withnormal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expressionof mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2’-deoxycytidine (5-azadC).Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrantmethylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas suchhypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression ofRASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylatedgroup (p﹤0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in theSkov3 cell line. Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation mayplay an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be avaluable molecular marker for the early detection of EOC.     

MTDH和VEGF在上皮性卵巢癌中的表达及临床意义

目的 探讨异黏蛋白（MTDH）及血管内皮生长因子（VEGF）在上皮性卵巢癌中的表达及其与上皮性卵巢癌临床病理特征的关系。方法 采用逆转录 聚合酶链反应（RT-PCR）及免疫组化SP法检测42例上皮性卵巢癌组（恶性组）、20例卵巢良性上皮性肿瘤组织（良性组）及15例正常卵巢上皮组织（正常组）中MTDH和VEGF mRNA及蛋白的表达,分析两者表达与上皮性卵巢癌临床病理特征的关系。结果 MTDH和VEGF mRNA在恶性组中的相对表达量分别为0.672±0.115和0.714±0.129,显著高于良性组（0.324±0.041、0.251±0.039）和正常组（0.317±0.035、0.243±0.031）,差异均有统计学意义（P＜0.01）。MTDH及VEGF蛋白在恶性组中的阳性表达率分别为69.0％、80.9％,显著高于良性组（20.0％、35.0％）和正常组（13.3％、20.0％）,差异均有统计学意义（P＜0.01）。MTDH和VEGF mRNA及蛋白的表达与上皮性卵巢癌的临床分期、淋巴结转移有关（P＜0.05）,而与病理类型及分化程度无关（P＞0.05）。在上皮性卵巢癌中MTDH与VEGF蛋白的表达呈正相关（r=0.420,P＜0.01）。 结论 MTDH和VEGF表达与上皮性卵巢癌的发生、发展有关。     

Prevalence of human papillomavirus in saliva of women with HPV genital lesions

Background

The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation.

Methods

Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA.

Results

The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes.

Conclusion

This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.

     

采用原位杂交法检测生殖系统尖锐湿疣和鳞状细胞癌内乳头瘤病毒的感染

目的　探讨HPV感染与生殖系统尖锐湿疣和鳞状细胞癌的关系。方法　采用HPV6 /11、16 /18原位杂交试剂盒 ,对 5 5例生殖系统不同病变中乳头瘤病毒感染状况进行分析检测。结果　 2 0例生殖系统尖锐湿疣 19例阳性 ,其中 17例为HPV6 /11型 ,2例为HPV16 /18型。 2 0例生殖系统鳞状细胞癌中 ,15例阳性 ,均为HPV16 /18型。 10例正常生殖系统鳞状上皮组织和 5例外阴白斑组织均呈阴性。结论　HPV6 /11多与生殖系统良性疣状病变有关 ,而HPV16 /18感染多见于生殖系统恶性病变。     

Prevalence of high--risk human papillomavirus infections in women with benign cervical cytology: a hospital based study from North India

INTRODUCTION: Cervical cancer is the commonest cancer among Indian women. High-risk human papillomavirus (HPV) detection holds the potential to be used as a tool to identify women, at risk for subsequent development of cervical cancer. There is a pressing need for identifying prevalence of asymptomatic cervical HPV infection in the local population. OBJECTIVE: To determine the prevalence of high-risk HPV DNA in women with benign cervical cytology. MATERIALS AND METHODS: Women visiting the gynecology outpatient with varied complaints were subjected to Pap smear. Four hundred and seventy two samples were subjected to polymerase chain reaction, using consensus primers for low and high-risk HPV (types 6, 11, 16, 18, 31 and 33). The samples that were positive for HPV DNA were subsequently assessed for high-risk consensus primers, types 16, 18, 31 and 33 as well as for HPV type 16 and 18. RESULTS: One hundred and seventy four (36.8%) women tested positive for HPV DNA. Thirty nine (8.2%) of the entire cohort tested positive for high-risk HPV. Fifteen samples were positive for type 16, 22 for type 18 and two for both types 16 and 18. A statistically higher prevalence of high-risk HPV was observed in poorly educated and rural groups. No association of HPV prevalence was noted with age, parity and age at marriage. CONCLUSION: The study generates epidemiological data of prevalence of sub-clinical HPV in the women visiting a tertiary care institute as well as peripheral health centres. The data generated will be useful for laying guidelines for mass screening of HPV, treatment and prophylaxis in the local population.     

HPV Genotyping Linear Assay Test Comparison in Cervical Cancer Patients: Implications for HPV Prevalence and Molecular Epidemiology in a Limited-resource Area in Bandung,Indonesia

Background: Persistent infection with high risk human papillomavirus (hrHPV) is strongly associated withcervical cancer. Normal cervical cells may also harbor hrHPV, and detection of early hrHPV infection mayminimize risk of cervical cancer development. This study aimed to compare two commercial HPV genotypingassays that may affordable for early screening in a limited-resource setting in Bandung, Indonesia. Materialsand Methods: DNA from cervical biopsies with histologically confirmed as squamous cell cervical cacinoma wereHPV genotyped by Linear Assay 1 (Roche Diagnostics, Mannheim, Germany) or Linear Assay 2 (Digene HPVGenotyping RH Test, Qiagen Gaithersburg, MD). In a subset of samples of each group, HPV genotype results werethen compared. Results: Of 28 samples genotyped by linear assay 1, 22 (78.6%) demonstrated multiple infectionswith HPV-16 and other hrHPV types 18, 45 and/or 52. In another set of 38 samples genotyped by linear assay 2,28 (68.4%) were mostly single infections by hrHPV type 16 or 18. Interestingly, 4 samples that had been testedby both kits showed discordant results. Conclusions: In a limited-resource area such as in Indonesia, countrywith a high prevalence of HPV infection a reliable cervical screening test in general population for early hrHPVdetection is needed. Geographical variation in HPV genotyping result might have impacts for HPV prevalenceand molecular epidemiology as the distribution in HPV genotypes should give clear information to assess theimpact of HPV prophylactic vaccines.     

MMP7蛋白及mRNA在卵巢上皮性肿瘤中的表达及意义

目的 探讨MMP7在上皮性卵巢癌组织中的表达及临床意义。方法 采用免疫组化方法及原位杂交方法检测10例正常卵巢组织、10例良性上皮性卵巢肿瘤组织和54例上皮性卵巢癌组织中MMP7蛋白的表达。结果 正常卵巢组织及良性卵巢肿瘤组织中,MMP7蛋白不表达;上皮性卵巢癌组织中,MMP7阳性表达率为88.89%。MMP7的表达与上皮性卵巢癌的临床分期和病理分级有关,与淋巴结转移无关。MMP7的mRNA与蛋白表达呈正相关(P＜0.0001)。结论 上皮性卵巢癌组织中,MMP7蛋白高度表达。MMP7蛋白在上皮性卵巢癌的发生过程中发挥着重要的作用,MMP7蛋白及mRNA表达水平可以作为判断卵巢癌预后的指标。     

Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer

It has been proposed that the frequent loss of heterozygosity (LOH) of an entire chromosome 17 contig in epithelial ovarian cancers (EOC) is the consequence of the inactivation of multiple tumour suppressor genes on this chromosome. We report the characterization of a 453 Kb 17q25 locus shown previously to exhibit a high frequency of LOH in EOC samples. LOH analysis further defined the minimal region of deletion to a 65 Kb interval flanked by D17S2239 and D17S2244, which contains RHBDF2, CYGB and PRCD as tumour suppressor gene candidates. Tissue specific expression excluded PRCD as a candidate. RHBDF2 was expressed at low levels in the majority of benign and low malignant potential (LMP) tumours, and in a subset of malignant ovarian tumour samples, as compared with primary cultures of normal ovarian surface epithelial cell (NOSE) samples. CYGB was expressed at low levels in the majority of LMP and malignant samples compared with benign and NOSE samples. In contrast to CYGB expression, RHBDF2 was expressed at low or undetectable levels in EOC cell lines exhibiting tumourigenic characteristics and up-regulated in a genetically modified EOC cell line rendered non-tumourigenic. DNA sequence analysis identified variants but no apparent deleterious mutations in either gene. Methylation-specific PCR analysis suggested that promoter methylation of CYGB but not RHBDF2 occurred in 6 of 31 malignant samples. The results combined suggest that RHBDF2 and CYGB may play distinctive roles in ovarian cancer and could be added to the growing roster of chromosome 17 genes implicated in this disease.     

Low Prevalence of HPV in Male Sexual Partners of HR-HPVInfected Females and Low Concordance of Viral Types inCouples in Eastern Guangdong

Objective: To investigate the prevalence of genital high-risk human papillomavirus (HR-HPV) in male sexualpartners of HR-HPV infected women and the concordance of viral types in couples in China, and comprehendthe role of men play in HPV transmission to women. Methods/Materials: 94 asymptomatic women and theirhusbands from rural Chaozhou participated in epidemiologic screening for HPV infection. Cervical cells fromfemales were collected for high risk HPV screening by real time-PCR, and they were positive for at least 1 of 13HR-HPV subtypes, then these samples were genotyped. Approximately one mouth later, penile epithelial cellsfrom 94 asymptomatic husbands were collected for HPV genotyping. At the same time, a cross-sectional studywas conducted in 366 male patients from sexually transmitted disease (STD) outpatient clinic in China for theprevalence of genital HR-HPV infection in men having frequent sex behavior. Penial epithelial cells were collectedfor HPV 6/11 and HPV 16/18 detection by fluorescent real-time quantified PCR. Results: Among 94 couples,the prevalence of genital HR-HPV infection in men whose wife was positive for cervical HR-HPV was 5.32%(5/94). Only 2.63% (2/76) had the same high risk viral type presented by their wife. HPV 16 proved to be themost prevalent viral type in men and in couples. Of 366 male patients from STD outpatient clinic, the prevalenceof HPV 16/18 infection in men with or without HPV 6/11 was 6.85% and 8.16%, respectively. The incidenceof HPV 16/18 was higher in men aged more than 35 years than the young men (18-35 years). Conclusion: Theprevalence of genital HR-HPV infection in male sexual partners of HPV-positive women in China was lowerthan that expected, and the concordance of high risk viral type between couples was extremely low. These datasuggested that infected men consitute an important viral reservoir, contributing to transmission of HR-HPV towomen and maintenance of infection, but HR-HPV infection may be less likely to persist in men than in women.     

Human Papillomavirus (HPV) Infection in Women Participating in Cervical Cancer Screening from 2006 to 2010 in Shenzhen City,South China

Purpose: Human papillomavirus (HPV) infection plays an important role in the development of cervicalcancer, but the prevalence of HPV infection in women of Shenzhen city remains unclear. The present study wasperformed to describe the change of cervical HPV infection in females who participated in voluntary cervicalcancer screening from 2006 to 2010 in Shenzhen city, China. Methods: A total of 4, 413 women were recruited.HPV infections were genotyped by polymerase chain reaction (PCR) and reversed dot blot hybridization inShenzhen Maternity and Child Health Hospital. Results: The prevalence of HPV infection was 13.8%. The fivemost commonly found HPV types were HPV16 (3.47%), HPV58 (1.68%), HPV33 (1.38%), HPV43 (1.36%) andHPV18 (1.27%). The secular trends of major HPV type-specific were diverse. Among of them, the prevalence ofHPV18 increased sharply while others increased slowly or even decreased in the period. The change of total HPV,single HPV and multiple HPV infection were similar during the five years. Conclusions: Our findings suggestedthat HPV infection is common with HPV16 and HPV 58 as the primary subtypes in women in Shenzhen city.The prevalence of HPV 18 infection is increasing faster than any others, which will lead it to be one of the mainsubtypes in this city in the future.     

诱骗受体3在上皮性卵巢癌组织中的表达及临床意义

目的:诱骗受体3(decoy receptor 3,DcR3)是肿瘤坏死因子受体(TNFR)家族的成员,影响着多种肿瘤的发生发展,本实验研究探讨其与卵巢癌发生发展及预后的关系。方法:应用免疫组织化学SP法检测38例正常卵巢组织、29例卵巢良性肿瘤及86例卵巢上皮性癌组织中DcR3蛋白的表达情况。结果:DcR3蛋白在卵巢癌组织中的表达明显高于卵巢良性肿瘤及正常组织中的表达;DcR3蛋白在卵巢上皮性癌Ⅰ-Ⅱ期表达较Ⅲ-Ⅳ期明显减弱;在高中分化组织中的表达明显低于低分化组织;在淋巴结转移组的表达高于无淋巴结转移组,各组间差异均具有统计学意义（P<0.05）。DcR3蛋白表达越强,患者生存时间越短（P<0.05）。结论:DcR3表达水平与卵巢上皮性癌临床分期、组织分化、肿瘤浸润、转移及预后有关,有可能成为一种卵巢癌肿瘤特异性指标。     

Identification of novel variant, 1484delG in the 3'UTR of H3F3B, a member of the histone 3B replacement family, in ovarian tumors

Previous studies have implicated the chromosomal region at 17q25 as harboring tumor suppressor genes based on the frequent loss of heterozygosity (LOH) observed in epithelial ovarian cancers (EOC). RT-PCR validation of Affymetrix GeneChip expression of H3F3B, a member of the 3B histone family that maps to 17q25.1, revealed a doublet band in cDNA from one of four EOC cell lines, OV90. In contrast to three other EOC cell lines (TOV81D, TOV112D and TOV21G) and primary cultures derived from normal ovarian surface epithelial cells (NOSE), sequence analysis of the cDNA revealed a deletion of G at position 1484 of the transcribed sequence which is located within the 3'UTR of H3F3B. OV90 was derived from ascites fluid of an undifferentiated adenocarcinoma of ovarian origin. The variant allele was identified in 1 of 65 (2%) healthy women with no prior history of cancer and in 5 participants with ovarian tumors comprising of 4 of 79 (5%) malignant EOC, none of 10 low malignancy potential tumors, and 1 of 8 (13%) benign tumors. All carriers of the variant alleles were heterozygous and tumor samples did not exhibit preferential LOH of the normal allele. The variant allele was identified in EOC samples of clear cell (1 of 20), mucinous (1 of 8), mixed cell (1 of 3) and undifferentiated (1 of 2) histopathological subtypes but none of 34 serous or 12 endometrioid subtype tumors. One of 3 mucinous benign tumors also harbored the variant allele. The functional significance of the variant is unknown, however its presence in rare subtypes of ovarian epithelial tumors warrants further investigation.     

人成纤维细胞生长因子类似表达基因和成纤维细胞生长因子2在上皮性卵巢肿瘤组织中的表达

目的 探讨人成纤维细胞生长因子类似表达基因(hSef)和成纤维细胞生长因子2(FGF-2)在上皮性卵巢肿瘤组织中的表达及二者的关系.方法 采用免疫组化SP法检测31例卵巢恶性上皮性肿瘤(卵巢癌组)、18例卵巢良性上皮性肿瘤(良性组)和10例正常卵巢组织(正常组)中hSef和FGF-2蛋白的表达.采用逆转录聚合酶链反应(RT-PCR)检测卵巢癌组、良性组和正常组各24例组织中hSef和FGF-2 mRNA的表达水平.结果 与良性组、正常组相比,卵巢癌组hSef蛋白呈低表达(P＜0.001),而FGF-2蛋白呈高表达(P=0.002).hSef蛋白与FGF-2蛋白的表达呈负相关(rs=-0.324,P=0.012).hSefmRNA在正常组、良性组、卵巢癌组的表达呈下降趋势,而FGF-2mRNA表达呈增高趋势(P ＜0.001).hSef mRNA和FGF-2 mRNA的表达呈负相关(正常组rs=-0.910,P＜0.001;良性组rs=-0.859,P＜0.001;卵巢癌组rs=-0.888,P＜0.001).结论 在卵巢癌组织中,hSef表达下降,FGF-2表达增强.hSef的低表达减弱了FGF-2对细胞的增殖作用,促进了卵巢肿瘤的发生与发展.