The role of EMMPRIN expression in ovarian epithelial carcinomas

Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas.

Methods: EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemisty.

Results: EMMPRIN siRNA treatment resulted in a lower growth, G₁ arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P < 0.05), and positively correlated with dedifferentiation and FIGO staging (P < 0.05). Immuhistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P < 0.05).

Conclusions: Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.     

WT-1、Smac蛋白在上皮性卵巢癌中的表达和临床意义研究

目的:探讨WT-1和Smac蛋白在上皮性卵巢癌中的表达及其临床意义。方法:应用免疫组织化学染色方法检测40例正常卵巢组织,40例卵巢上皮性良性肿瘤组织,60例全面分期手术治疗的上皮性卵巢癌组织中WT-1、Smac蛋白的表达,并分析WT-1、Smac蛋白的表达与上皮性卵巢癌临床病理特征的相关性及二者之间的相关性。结果:WT-1蛋白在上皮性卵巢癌组织中的表达明显高于正常卵巢组织或卵巢上皮性良性肿瘤组织(P0.05);Smac蛋白在上皮性卵巢癌组织中表达明显低于正常卵巢组织或卵巢上皮性良性肿瘤组织(P0.05)。上皮性卵巢癌组织中WT-1、Smac蛋白的表达与肿瘤临床分期、组织分化程度、淋巴结有无转移均显著相关(P0.05)。且上皮性卵巢癌中WT-1、Smac蛋白的表达呈明显负相关性(r=-0.35,P0.05)。结论:WT-1蛋白高表达或Smac蛋白低表达可能在上皮性卵巢癌的发生、发展中发挥重要作用,检测WT-1、Smac蛋白的表达有助于上皮性卵巢癌恶性程度的判断和预后评估。     

EGFR和KRAS在上皮性卵巢癌组织中的表达及临床意义

目的:探讨表皮生长因子受体(EGFR)和鼠Kirsten肉瘤病毒致癌基因(KRAS)蛋白在上皮性卵巢癌组织中的表达水平及临床意义。方法:利用免疫组化SP法对上皮性卵巢癌组织(病例组,n=57)、卵巢良性肿瘤组织(良性组,n=50)以及正常卵巢组织(对照组,n=50)中的EGFR、KRAS蛋白水平进行检测,并分析其在上皮性卵巢癌发生发展中的作用。结果:病例组的EGFR、KRAS蛋白阳性率高于良性组和对照组(P0.05),良性组和对照组的EGFR、KRAS蛋白阳性率差异无统计学意义(P0.05)。浆液性腺癌组EGFR、KRAS蛋白的阳性表达率高于非浆液性腺癌组,Ⅲ~Ⅳ期的上皮性卵巢癌组织中EGFR、KRAS蛋白阳性表达率高于Ⅰ~Ⅱ期,中、低分化组中EGFR、KRAS蛋白阳性表达率高于高分化组,差异均具有统计学意义(P0.05)。上皮性卵巢癌组织中EGFR与KRAS的蛋白的阳性表达率呈正相关关系(r=0.469,P0.05)。结论:EGFR及KRAS蛋白在上皮性卵巢癌组织中的表达水平明显升高,可能参与了上皮性卵巢癌的发生发展过程,且两者之间呈正相关关系,联合检测可作为早期诊断上皮性卵巢癌的重要指标。     

转录因子FOXM1在上皮性卵巢癌中的表达及临床意义

FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关.     

The O-Linked Glycome and Blood Group Antigens ABO on Mucin-Type Glycoproteins in Mucinous and Serous Epithelial Ovarian Tumors

Background

Mucins are heavily O-glycosylated proteins where the glycosylation has been shown to play an important role in cancer. Normal epithelial ovarian cells do not express secreted mucins, but their abnormal expression has previously been described in epithelial ovarian cancer and may relate to tumor formation and progression. The cyst fluids were shown to be a rich source for acidic glycoproteins. The study of these proteins can potentially lead to the identification of more effective biomarkers for ovarian cancer.

Methods

In this study, we analyzed the expression of the MUC5AC and the O-glycosylation of acidic glycoproteins secreted into ovarian cyst fluids. The samples were obtained from patients with serous and mucinous ovarian tumors of different stages (benign, borderline, malignant) and grades. The O-linked oligosaccharides were released and analyzed by negative-ion graphitized carbon Liquid Chromatography (LC) coupled to Electrospray Ionization tandem Mass Spectrometry (ESI-MSⁿ). The LC-ESI-MSⁿ of the oligosaccharides from ovarian cyst fluids displayed differences in expression of fucose containing structures such as blood group ABO antigens and Lewis-type epitopes.

Results

The obtained data showed that serous and mucinous benign adenomas, mucinous low malignant potential carcinomas (LMPs, borderline) and mucinous low-grade carcinomas have a high level of blood groups and Lewis type epitopes. In contrast, this type of fucosylated structures were low abundant in the high-grade mucinous carcinomas or in serous carcinomas. In addition, the ovarian tumors that showed a high level of expression of blood group antigens also revealed a strong reactivity towards the MUC5AC antibody. To visualize the differences between serous and mucinous ovarian tumors based on the O-glycosylation, a hierarchical cluster analysis was performed using mass spectrometry average compositions (MSAC).

Conclusion

Mucinous benign and LMPs along with mucinous low-grade carcinomas appear to be different from serous and high-grade mucinous carcinomas based on their O-glycan profiles.     

Co-Expression of Lewis y Antigen with Human Epididymis Protein 4 in Ovarian Epithelial Carcinoma

Objective

The main aims of this study were to explore the molecular structural relationship between Human epididymis protein 4 (HE4) and Lewis y antigen by determining their expression patterns and clinical significance in ovarian epithelial carcinoma.

Methods

The structural relationship between HE4 and Lewis y antigen was examined using immunoprecipitation and confocal laser scanning microscopy. HE4 and Lewis y were detected in tissues from malignant (53 cases), borderline (27 cases), benign (15 cases) and normal ovarian tissues (15 cases) using immunohistochemical analysis.

Results

HE4 was present in ovarian cancer, benign tumor tissues, ovarian carcinoma cells, and culture medium, and contained Lewis y antigen. Moreover, expression of Lewis y antigen in HE4 from ovarian cancer was higher than that from benign tumor (P<0.05). HE4 possibly exists as two protein isoforms, both containing Lewis y antigen. Our immunohistochemistry data revealed significantly higher positive expression rates of HE4 in malignant ovarian tissues, compared to benign tumor and normal tissue (P<0.05), similar to Lewis y antigen levels in ovarian cancer (P<0.05). Notably, tissues displaying marked expression of HE4 simultaneously expressed high levels of Lewis y antigen. A linear correlation between the expression patterns of HE4 and Lewis y antigen was evident. Consistently, double-labeling immunofluorescence experiments illustrated co-localization of HE4 and Lewis y antigen within the same area.

Conclusions

HE4 contains Lewis y antigen. Our results further demonstrate a close correlation between the expression levels of the two antigens, which are significantly high in ovarian cancer.     

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Human cytomegalovirus (HCMV) has been detected in various types of tumors. We studied the prevalence of HCMV in ovarian cancer and its relation to clinical outcome. Paraffin-embedded tissues obtained prospectively from 45 patients with ovarian cancer and 30 patients with benign ovarian cystadenoma were analyzed for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Plasma was analyzed for HCMV serology. HCMV-IgG levels were higher in patients with ovarian cancer or benign cystadenoma than in age-matched controls (P?=?.002, P?<?.0001, respectively). HCMV IgM was detected in 12% of ovarian cancer patients and 3% of patients with benign tumors but was absent in controls. In patients with ovarian cancer, higher IgG levels were associated with better outcomes (P?=?.04). Extensive HCMV-IE protein expression was detected in 75% of ovarian cancers and 26% of benign tumors; pp65 was detected in 67% of ovarian cancers and 14% of benign tumors. A higher grade of HCMV infection was associated with higher stage of disease. Extensive HCMV-pp65 expression was associated with shorter median overall survival than focal expression (39 versus 42.5?months, P?=?.03). At study closure, 58% of ovarian cancer patients with focal pp65 expression were alive versus 27% of patients with extensive pp65 expression (P?=?.03). Thus, HCMV proteins are detected at different levels in ovarian tumors and benign cystadenomas. Ovarian cancer patients with focal HCMV-pp65 expression in their tumors and high IgG levels against HCMV lived longer, highlighting a need for in-depth studies of the oncomodulatory role of HCMV in ovarian cancer.     

卵巢上皮肿瘤淋巴转移与血管内皮生长因子C的表达

The aim of the present study was to explore the role of vascular endothelial growth factor-C (VEGF-C) in the process of angiogenesis, lymphangiogenesis and lymphatic metastasis in epithelial ovarian tumors. In situ hybridization and immunohistochemical staining for VEGF-C were performed in 30 epithelial ovarian carcinomas, 9 borderline tumors and 26 benign cystadenomas. Endothelial cells were immunostained with anti-VEGFR-3 pAb and anti-CD31 mAb, and VEGFR-3 positive vessels and microvessel density (MVD) were assessed by image analysis. VEGF-C mRNA and protein expression in ovarian epithelial carcinomas were significantly higher than that in borderline tumors and benign cystadenomas (p < 0.05 or p < 0.01). In ovarian epithelial carcinomas, VEGF-C protein expression, VEGFR-3 positive vessels and MVD were significantly higher in the cases of clinical stage III-IV and with lymphatic metastasis than those of clinical stage I-II and without lymphatic metastasis respectively (p < 0.05 or p < 0.01), VEGFR-3 positive vessels and MVD was significantly higher in the VEGF-C protein positive tumors than negative tumors (p < 0.05), VEGFR-3 positive vessels was significantly correlated with MVD(p < 0.01). These data suggest that VEGF-C might play a role in lymphatic metastasis via lymphangiogenesis and angiogenesis in epithelial ovarian carcinomas, and VEGF-C could be used as a biologic marker of metastasis in ovarian epithelial carcinomas.     

上皮性卵巢癌患者血清及肿瘤中Prostasin变化及意义

目的：检测prostasin在上皮性卵巢癌患者血清及组织中的表达,探讨prostasin在上皮性卵巢癌中的临床意义。方法：运用免疫组织化学发检测组织prostasin在20例正常卵巢组织、40例卵巢上皮性良性肿瘤以及26例卵巢癌中的表达,分析其与各临床参数间的相关性,并通过ELISA法检测26例上皮性卵巢癌患者血清prostasin水平,探讨血清prostasin与组织prostasin的相关性。结果：prostasin在正常卵巢组织中无表达,在卵巢良性及恶性肿瘤中的表达率分别为24．00％和71．47％,差异具有统计学意义（x2=16．37,P〈0．005）;prostasin表达与病理类型、分化程度呈正相关（P=0．001,P=0．002）,与临床分期无明显相关性（P=0．154）;血清prostasin在卵巢上皮性癌组为14．07μg／ml,明显高于良性肿瘤组及正常对照组（P〈0．001）;卵巢癌组术后7天血清prostasin水平7．88μg／ml,明显低于术前（P=0．000）;术前血清prostasin浓度与组织prostasin表达呈线性相关（r=0．601）。结论：prostasin对上皮性卵巢癌的发生发展、诊断及预后评估具有意义。     

上皮性卵巢癌患者组织P53、Ki67表达及其临床意义

摘要 目的：探讨上皮性卵巢癌患者组织P53、Ki67表达及其临床意义。方法：选择卵巢肿瘤102例,其中病理诊断为良性卵巢肿瘤40例(良性组)和上皮性卵巢癌62例(恶性组),采用免疫组化法检测组织P53、Ki67表达水平,调查患者的临床病理特征并进行相关性分析。结果：恶性组的P53、Ki67表达阳性率为80.6 %和72.6 %,显著高于良性组的10.0 %和12.5 %(P<0.05)。在恶性组中,不同浸润转移、分化程度、病理分期患者的P53、Ki67表达阳性率对比差异有统计学意义(P<0.05)。直线相关分析显示上皮性卵巢癌患者P53表达阳性率与Ki67表达阳性率呈现显著正相关性(r=0.872,P=0.000)。多因素logistic回归分析显示浸润转移、分化程度、病理分期都为影响P53、Ki67表达阳性率的主要因素(P<0.05)。结论：上皮性卵巢癌患者组织P53、Ki67都呈现高表达状况,与患者的临床病理特征显著相关,两者也可互相影响,共同参与上皮性卵巢癌的发生与发展。     

中国人卵巢上皮性肿瘤nm23H1基因遗传不稳定性的研究

The aim of this study was to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in the epithelial ovarian tumors, which may provide experimental basis for the mechanism of nm23H1 gene and tumor metastasis. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 gene. In our experiments, the frequency of heredity instability of malignant ovarian tumors was 40%, which is higher than that of borderline ovarian tumors, while there were no heredity instability occurred in benign ovarian tumors and normal ovarian tissue. Among 25 epithelial ovarian carcinomas, the frequency of LOH in lymph node metastasis cases (66.67%) was significantly higher than those without metastasis (10.53%). Moreover, the frequency of LOH was higher in FIGO stage III and IV than in stage I and II. However, the frequency of MSI showed no correlation with any clinicopathologic characteristics. The positive frequency of nm23H1 protein in the ovarian epithelial carcinoma and borderline tumors were 56.00% and 57.14%, respectively. They were both higher than those of the benign tumors and normal ovarian tissue. In the epithelial ovarian carcinomas, the positive frequency of nm23H1 protein in lymph node metastasis case was significantly lower than those without metastasis. FIGO stage III and IV also exhibited lower positive frequency of nm23H1 protein compared with stage I and II. Furthermore, there was no difference in nm23H1 protein expression intensity analyzed by computer imaging. In the epithelial ovarian carcinomas, the positive frequency of nm23H1 protein in LOH positive group was 0.00%, which is lower than that of LOH negative group (P < 0.01). The results indicated that the heredity instability of nm23H1 gene might be implicated in pathogenesis and progression of epithelial ovarian tumor. The occurrence of LOH might be the molecule marker of the deteriorism of ovarian tissue. Both MSI and LOH of nm23H1 gene controlled development of the epithelial ovarian tumor independently in different paths. LOH could inhibit the expression of nm23H1 in local tissue of the epithelial ovarian carcinoma, which endowed it with high aggressive and poor prognosis. Increasing the amount of nm23H1 protein expression could effectively restrain metastasis of the ovarian epithelial carcinoma and improve prognosis of patients.     

趋化因子受体CCR3在上皮性卵巢癌中的表达及临床意义

目的:探讨趋化因子受体CCR3在上皮性卵巢癌组织中的表达情况,以及其与卵巢癌临床病理特征的关系。方法:收集上皮性卵巢癌组织、良性上皮性卵巢肿瘤组织以及正常卵巢组织标本各30例,采用多聚腺苷酸加尾实时荧光定量反转录聚合酶链反应[poly(A)-RT-qPCR]检测其CCR3的表达,并分析上皮性卵巢癌组织中CCR3的表达与患者临床病理特征之间的关系。结果:上皮性卵巢癌组织中CCR3的表达显著高于良性卵巢肿瘤组和正常卵巢组,差异有统计学意义(P0.05);且上皮性卵巢癌组织中CCR3的表达与患者的分期、组织分级及淋巴结转移均显著相关(P0.05)。结论:CCR3在上皮性卵巢癌组织中呈高表达,且在上皮性卵巢癌的发生和发展过程中均起着十分重要的作用。     

Nerve growth factor induces the expression of chaperone protein calreticulin in human epithelial ovarian cells

Epithelial ovarian cancer is highly angiogenic and high expression of Nerve Growth Factor (NGF), a proangiogenic protein. Calreticulin is a multifunctional protein with anti-angiogenic properties and its translocation to the tumor cell membrane promotes recognition and engulfment by dendritic cells. The aim of this work was to evaluate calreticulin expression in human normal ovaries, benign and borderline tumors, and epithelial ovarian cancer samples and to evaluate whether NGF regulates calreticulin expression in human ovarian surface epithelium and in epithelial ovarian cancer cell lines. Calreticulin mRNA and protein levels were analyzed using RT-PCR, Western blot and immunohistochemistry in 67 human ovarian samples obtained from our Institution. Calreticulin expression induced by NGF stimulation in cell lines was evaluated using RT-PCR, Western blot and immunocytochemistry. We found a significant increase of calreticulin mRNA levels in epithelial ovarian cancer samples as compared to normal ovaries, benign tumors, and borderline tumors. Calreticulin protein levels, evaluated by Western blot, were also increased in epithelial ovarian cancer with respect to benign and borderline tumors. When HOSE and A2780 cell lines were stimulated with Nerve Growth Factor, we found an increase in calreticulin protein levels compared to controls. This effect was reverted by GW441756, a TRKA specific inhibitor. These results suggest that NGF regulates calreticulin protein levels in epithelial ovarian cells through TRKA receptor activation.     

上皮性卵巢癌中Maspin蛋白与血管内皮生长因子-C的表达及其相关性

目的：探讨上皮性卵巢癌组织中maspin蛋白与血管内皮生长因子-C（VEGF-C）表达的临床意义及其相关性。方法：采用免疫组化技术检测75例上皮性卵巢癌中maspin蛋白与VEGF-C的表达情况,以卵巢良性肿瘤及正常卵巢作为对照。结果：maspin和VEGF-C在上皮性卵巢癌中的阳性表达率分别为61.3%、82.7%,均明显高于卵巢良性肿瘤（13.3%、20%）和正常卵巢组织（0%、0%）,maspin蛋白在上皮性卵巢癌中的表达与FIGO分期高、组织学分级高、腹水形成和淋巴结转移有关;VEGF-C与FIGO分期高、淋巴结转移和腹水形成有关;上皮性卵巢癌中maspin蛋白与VEGF-C的表达成正相关。结论：maspin和VEGF-C在上皮性卵巢癌中表达上调,在卵巢上皮性癌的浸润、转移中起重要作用。     

Inhibition of Ovarian Epithelial Carcinoma Tumorigenesis and Progression by microRNA 106b Mediated through the RhoC Pathway

Epithelial ovarian cancer (EOC) is the most lethal of the gynecological malignancies. Exploring the molecular mechanisms and major factors of invasion and metastasis could have great significance for the treatment and prognosis of EOC. Studies have demonstrated that microRNA 106b (miR-106b) may be a promising therapeutic target for inhibiting breast cancer bone metastasis, but the role of miR-106b in EOC is largely unknown. In this work, miRNA-106b expression was quantified in various ovarian tissues and tumors. Ovarian carcinoma cell lines were transfected with miR-106b, after which, cell phenotype and expression of relevant molecules was assayed. Dual-luciferase reporter assays and xenograft mouse models were also used to investigate miR-106b and its target gene. MiR-106b mRNA expression was found to be significantly higher in normal ovarian tissues and benign tumors than in ovarian carcinomas and borderline tumors (p < 0.01), and was negatively associated with differentiation (Well vs. Por & Mod) and the International Federation of Gynecology and Obstetrics (FIGO) staging (stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). MiR-106b transfection reduced cell proliferation; promoted G1 or S arrest and apoptosis (p < 0.05); suppressed cell migration and invasion (p < 0.05); reduced Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6K), Bcl-xL, Matrix metallopeptidase 2 (MMP2), MMP9 mRNA and protein expression; and induced p53 expression (p < 0.05). Dual-luciferase reporter assays indicated that miR-106b directly targets RhoC by binding its 3’UTR. MiR-106b transfection also suppressed tumor development and RhoC expression in vivo in xenograft mouse models. This is the first demonstration that miR-106b may inhibit tumorigenesis and progression of EOC by targeting RhoC. The involvement of miR-106b-mediated RhoC downregulation in EOC aggression may give extended insights into molecular mechanisms underlying cancer aggression. Approaches aimed at overexpressing miR-106b may serve as promising therapeutic strategies for treating EOC patients.     

NDRG2在上皮性卵巢癌中的表达及与预后的关系

目的:探讨NDRG2在上皮性卵巢癌中的表达及其与预后的关系。方法:收集新鲜的上皮性卵巢癌和正常卵巢组织各15例,采用real-time PCR检测和比较其NDRG2 m RNA的表达。收集上皮性卵巢癌病理切片96例进行免疫组化检测其NDRG2蛋白的表达,并收集患者的临床病理资料,随访患者的生存情况,分析NDRG2蛋白的表达与上皮性卵巢癌患者临床病理特征和预后的关系。结果:上皮性卵巢癌组织中NDRG2 mRNA和蛋白的表达均显著低于正常卵巢组织(P0.05)。NDRG2在上皮性卵巢癌组织中的表达随着上皮性卵巢癌病理分期的升高而降低,而且其表达降低和患者不良预后显著相关(P=0.002),但其表达和不同上皮性卵巢癌的病理类型、分化程度以及年龄均无明显相关性。去除手术病理分期的影响,NDRG2表达下调和肿瘤细胞减灭术的满意程度以及术后规范化疗是三个影响上皮性卵巢癌预后的重要因素。结论:NDRG2在上皮性卵巢癌中的表达下降,并与患者的不良预后呈显著正相关。     

Decreased Expression of Beclin 1 Correlates Closely with Bcl-xL Expression and Poor Prognosis of Ovarian Carcinoma

Background

It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.

Methodology/Principal Findings

In the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.

Conclusions/Significance

Our findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.     

Nucleostemin基因在卵巢上皮性肿瘤的表达及与病理分型的关系

目的：研究核干细胞因子Nucleostemin（NS）基因在卵巢上皮性肿瘤中的表达,探讨其与肿瘤病理分型的关系。方法：采用RT-PCR及Western blot检测36例卵巢癌组织手术标本,32例卵巢良性上皮肿瘤组织手术标本,12例正常卵巢组织标本中Nu-cleostemin基因及相应蛋白的表达,采用分组对照的方法对比3组样本中NS基因及蛋白的表达情况,并进行相对定量研究。采用统计学方法检测NS基因的表达是否与临床病理分级及血清CA125存在关联。结果：①卵巢癌组织中NS的阳性表达率显著高于良性肿瘤组织及正常卵巢组织;②卵巢癌组织中,淋巴结转移组NS的表达水平高于未转移组;③临床分期Ⅲ期组的表达水平高于ⅠB期组;④中、低分化组的表达水平高于高分化组。结论：卵巢癌组织中存在NS基因的高表达,其表达量与组织类型无关,而与临床TNM分期及组织分级正相关。     

Expression of serum amyloid A, in normal, dysplastic, and neoplastic human colonic mucosa: implication for a role in colonic tumorigenesis.

Serum amyloid A (SAA) is an acute phase reactant, whose level in the blood is elevated in response to trauma, infection, inflammation, and neoplasia. Elevated levels of SAA in the serum of cancer patients were suggested to be of liver origin rather than a tumor cell product. The role of SAA in human malignancies has not been elucidated. We investigated the expression of SAA at various stages of human colon carcinoma progression. Nonradioactive in situ hybridization applied on paraffin tissue sections from 26 colon cancer patients revealed barely detected SAA mRNA expression in normal looking colonic epithelium. Expression was increased gradually as epithelial cells progressed through dysplasia to neoplasia. Deeply invading colon carcinoma cells showed the highest levels of SAA. Expression was also found in colon carcinoma metastases. Cells of lymphoid follicles of the intestinal wall, inflammatory cells, ganglion cells, and endothelial cells, also expressed SAA mRNA. Immunohistochemical staining revealed SAA protein expression that colocalized with SAA mRNA expression. RT-PCR analysis confirmed the expression of the SAA1 and SAA4 genes in colon carcinomas, expression that was barely detectable in normal colon tissues. These findings indicate local and differential expression of SAA in human colon cancer tissues and suggest its role in colonic tumorigenesis.     

HE4、ALDH1、CD44在卵巢良恶性肿瘤鉴别诊断中的检测效能观察

摘要 目的：观察人附睾蛋白4（HE4）、乙醛脱氢酶1（ALDH1）、黏附分子CD44在卵巢良恶性肿瘤鉴别诊断中的检测效能。方法：选取2020年1月~2022年5月我院收治的100例卵巢癌患者、100例卵巢良性肿瘤患者，分为纳入恶性组与良性组，另外选取同期体检的100例健康女性作为对照组。比较三组患者血清中HE4、ALDH1及组织中CD44的表达情况，并采用受试者工作特征（ROC）曲线分析其对卵巢良恶性肿瘤的鉴别诊断价值。结果：恶性组患者的HE4、ALDH1水平及CD44阳性表达率均高于良性组与对照组（P＜0.05），良性组患者的HE4、ALDH1水平及CD44阳性表达率高于对照组（P＜0.05）。与临床分期为Ⅰ~Ⅱ期、未发生淋巴转移患者比较，临床分期为Ⅲ~Ⅳ期、发生淋巴转移的卵巢癌患者HE4、ALDH1水平及CD44阳性表达率更高（P＜0.05），Spesrman相关性分析结果显示，HE4、ALDH1水平及CD44阳性表达率均与卵巢癌患者临床分期、淋巴转移成正相关（P＜0.05）。ROC特征曲线结果显示，HE4、ALDH1、CD44鉴别卵巢良恶性肿瘤的曲线下面积（AUC）分别为0.837、0.768及0.610，采用3项指标联合（并联）鉴别卵巢良恶性肿瘤的AUC及敏感度均高于单一指标诊断（P＜0.05）。结论：卵巢恶性肿瘤患者血清中HE4、ALDH1及组织中CD44均呈现高表达，且表达水平与卵巢癌患者临床分期、淋巴转移密切相关，HE4、ALDH1联合CD44检测对卵巢良恶性肿瘤具有较高的的鉴别诊断价值。