Immunologic studies on the cystic effusions of ovarian epithelial neoplasms.

Cystic effusions from 12 epithelial tumors of the ovary and pooled normal ovarian tissue were studied by immunodiffusion for the presence of immunoglobulins G (IgG), M (IgM), and A (IgA) and free secretory component (FSC). In pooled normal ovarian tissue, IgG was the only immunoglobulin detected. In the neoplastic samples studied, IgG was detected in each of the 12 samples (100%), IgM was found in 10 of the 12 samples (83%), and IgA was detected in 11 of the 12 samples (92%). There was no discernible correlation between the immunoglobulins detected and the composition of the effusions or the pathologic classification of the tumors. FSC was detected in all mucinous samples studied, malignant as well as benign. This substance was not detected in any of the nonmucinous samples or in pooled normal ovarian tissue. The data suggest a correlation between the presence of FSC and the mucinous composition of the tumor effusion. Possible use of FSC assays in the study of mucinous tumors of the ovary is discussed.     

Quantitation of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in the effusions of ovarian epithelial neoplasms.

OBJECTIVE: Our objective was to determine the presence and quantities of multifunctional cytokines in cyst and ascites fluids obtained from patients with ovarian cancer. STUDY DESIGN: Cyst and ascites fluids obtained from 35 patients with ovarian epithelial neoplasms were analyzed for the multifunctional cytokines tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. The fluids were classified on the basis of the pathologic diagnosis of the tumor tissue. Data were evaluated by analysis of variance. RESULTS: The fluids from patients with papillary forms of adenocarcinoma had high levels of all three cytokines when compared with all other pathologic groups. Interleukin-6 was significantly higher than tumor necrosis factor-alpha or interleukin-1 beta in fluids from all diagnostic categories (p < 0.01). Interleukin-6 levels were significantly higher in fluids from patients with papillary serous cystadenocarcinoma (817 +/- 137 pg/ml) and papillary adenocarcinoma (838 +/- 171 pg/ml) (p < 0.01). Interleukin-1 beta was significantly elevated (p < 0.01) in neoplastic effusions from papillary serous cystadenocarcinomas (53 +/- 8 pg/ml), mucinous cystadenomas (51 +/- 12 pg/ml), and endometrioid carcinomas (54 +/- 18 pg/ml). Tumor necrosis factor-alpha was highest in fluids from patients with papillary adenocarcinoma (46.2 +/- 22.8 pg/ml); however, these levels were not significantly different from the mean quantities of tumor necrosis factor-alpha in other fluids. CONCLUSIONS: The detection of interleukin-1 beta and interleukin-6 in neoplastic effusions provides possible evidence for a host immune response to ovarian cancer. These multifunctional cytokines have been implicated in growth stimulation and cytotoxicity of ovarian tumor cells.     

Detection of human ovarian tumor-associated antigens by antibodies isolated from ovarian carcinoma ascitic fluid

Ascitic fluid from patients with ovarian epithelial cancer contains large amounts of soluble immune complexes and is a potential source of antibodies and antigens associated with the tumor. The antibodies against tumor-associated antigens were purified from the ascitic fluids of patients with ovarian serous cystadenocarcinoma. These antibodies showed specificity toward ovarian epithelial cancer when tested against ovarian tumor cell lines and paraffin-embedded tissue sections of ovarian cancer. The antigens in sera of patients were separated from IgG and IgG complexes by affinity chromatography and the free antigens were isolated. With the antibodies purified from ascitic fluid, the levels of tumor-associated antigens in sera of 10 patients with serous cystadenocarcinoma and 12 control patients were detected by an enzyme-linked immunosorbent assay. The antigens in patients with ovarian epithelial cancer were 2 to 10 times higher than those in control patients. These studies demonstrate that the antibodies isolated from ascitic fluid detect the tumor-associated antigens on tumor cells as well as the shed antigens present in serum.     

Role of human papillomavirus in the development of epithelial ovarian neoplasms in Italian women

AIM: In this article, for the first time, we investigate the presence of human papillomavirus (HPV) DNA in ovarian epithelial neoplasms from a group of 71 Italian women. The follow ups of the patients with or without HPV DNA were also considered to evaluate whether HPV DNA in these tumors could be an indicator of prognosis. METHODS: HPV DNA was evaluated by polymerase chain reaction (PCR). Additionally P16 immunoreactivity was evaluated in all positive cases to demonstrate the presence of HPV. RESULTS: Only three cases out of 71 epithelial ovarian neoplasms (4.22%) in this series were weakly HPV positive. The presence of HPV DNA in these cases did not seem to be related with the type of neoplasm, their grade of differentiation, staging of development, patient's age or survival. CONCLUSION: The presence of HPV could be an expression of a latent infection. In both positive and negative HPV ovarian neoplasms, cervix showed only chronic cervicitis and no signal for HPV DNA on PCR analysis.     

卵巢上皮性肿瘤cyclinE表达的临床意义

目的 :检测卵巢上皮性肿瘤中cyclinE的表达 ,分析其临床意义。方法 :应用免疫组化S -P法检测cyclinE在 2 0例良性、10例交界性、55例恶性卵巢上皮性肿瘤中的表达情况 ,并分析它们与临床病理指标的关系。结果 :cyclinE在良性、交界性、恶性卵巢上皮性肿瘤中表达总阳性率分别为 30 %、50 %、78.18% ,强阳性率分别为 10 %、2 0 %、4 3.6 % ,差异均有显著性。在恶性卵巢上皮性肿瘤中cyclinE阳性表达与低组织分化 ,淋巴结转移及腹水显著有关 (P <0 .0 5) ,cyclinE阳性的肿瘤细胞多发生转移 ,预后差。结论 :cyclinE在卵巢上皮性肿瘤中的表达 ,可作为估计卵巢肿瘤恶性程度和预后的重要指标之一     

Seprase在上皮性卵巢癌胸腹水中的表达及其临床预后意义

目的 探讨Seprase在上皮性卵巢癌胸腹水癌细胞中的表达及其临床预后意义。方法 选择郑州大学第一附属医院和挪威奥斯陆大学附属肿瘤医院2001-2003年住院的65例上皮性卵巢癌患者的胸腹水标本75份，采用免疫组化技术检测了65份卵巢癌腹水和10份胸水细胞石蜡包埋组织中Seprase蛋白的表达，并对其中34份新鲜腹水细胞进行免疫印迹分析，同时检测9份良性腹水脱落细胞作为对照。结果 上皮性卵巢癌胸腹水中Seprase蛋白阳性表达率77．33％（58／75），显著高于良性胸腹水的22．22％（2／9），P〈0．01。Seprase蛋白的表达与卵巢癌患者年龄、FIGO分期、组织学分级和组织学类型无关，而与患者预后呈负相关（P〈0．05）。蛋白印迹表明27／34样本中同时检测到170ku Seprase二聚体和97ku单体，1份仪表达170ku Seprase二聚体。结论 Seprase参与了卵巢癌的发生发展，并与患者不良预后有关，可能成为卵巢癌的预后指标。     

肿瘤相关粘蛋白MUC1及其mRNA与卵巢上皮性肿瘤关系的研究

目的 :初步探讨肿瘤相关粘蛋白MUC1基因及其蛋白与卵巢上皮性肿瘤的关系。方法 :采用原位杂交法和免疫组化ABC法 ,检测 6 5例卵巢上皮性肿瘤组织和 8例正常卵巢组织MUC1mRNA及其蛋白的表达。结果 :MUC1mRNA和MUC1阳性表达皆位于胞浆和胞膜 ,多呈灶状分布。MUC1mRNA和MUC1在卵巢癌中的检出率分别为 75 .6 % ,80 .0 % ,显著高于良性上皮性肿瘤的 4 0 % ,4 5 %和正常卵巢组织的 2 5 .0 % ,37.5 % (P <0 .0 0 5 )。二者高表达与卵巢癌的期别晚、组织分化差及淋巴结转移有关。结论 :MUC1作为新型肿瘤标志物 ,与卵巢癌的发生、发展密切相关     

An immunohistochemical study of the incidence and significance of human chorionic gonadotrophin synthesis by epithelial ovarian neoplasms

In an immunohistochemical study of the presence of the beta subunit of human chorionic gonadotrophin (hCG) in ovarian neoplasms it was found that hCG was detectable in 42% of ovarian epithelial tumors, an incidence of hCG synthesis which very closely approximates that found in radioimmunoassay studies. There was no relationship between the capacity of an ovarian neoplasm to synthesize hCG and the histologic type of the tumor, the degree of malignancy of the neoplasm, or the prognosis.     

Quantitation of immunoglobulin A in the human chorioamniotic membrane

Thirty-eight chorioamniotic membranes were obtained from normal patients divided into three groups according to time of rupture. A protein extract was obtained by destruction and differential centrifugation and immunoglobulin A was measured by the method of Mancini. The authors demonstrated that it is possible to quantitate immunoglobulin A. No statistically significant differences were observed between groups.     

溶血磷脂酸受体在卵巢癌细胞系3AO、OVCAR3、SKOV3及卵巢癌组织中的表达

目的:研究溶血磷脂酸受体在人卵巢癌细胞系和人卵巢癌组织中蛋白的表达。方法:用免疫细胞化学和免疫组织化学法检测LPA1,LPA2和LPA3蛋白在人卵巢癌细胞系3AO、OVCAR3、SKOV3和人卵巢癌组织中的表达水平。结果:免疫细胞化学显示LPA1,LPA2和LPA3蛋白在人卵巢癌细胞系中均有表达;免疫组织化学显示LPA1蛋白在正常卵巢上皮和卵巢良性肿瘤中高表达,LPA2和LPA3蛋白在人卵巢癌组织中高表达。结论:LPA1,LPA2和LPA3在人卵巢癌细胞系和人卵巢癌组织中均有广泛表达;LPA2,LPA可能与卵巢癌的发生发展密切相关。     

Anion transport by human placenta: a study of chloride and sulphate efflux from isolated placental tissue fragments.

The efflux of radiolabelled sulphate and chloride from fragments prepared from normal human term placentae has been examined so that a comparison between the transport properties of whole tissue and isolated placental membranes may be made. Sulphate efflux was found via a temperature- and DIDS sensitive mechanism. External chloride and sulphate were able to trans-accelerate the egress of labelled sulphate from tissue fragments via a DIDS-inhibitable route. These results are consistent with sulphate transport being mediated via an anion-exchange process. Chloride efflux from fragments of placenta was via a system which could be trans-stimulated by external Cl-: this moiety of transport was inhibited by DIDS. Several differences between the characteristics of placental tissue anion transport and isolated membrane vesicles were noted and are discussed.     

Isolation of human spermatozoa membrane antigens binding sperm-immobilizing and sperm-agglutinating antibodies.

Peptides of human spermatozoa were dissolved with Hyamine 2389 and Triton X-100 and separated by chromatography on Biogel P4 columns into seven fractions. The antigenic activities of the separated sperm-membrane fractions were tested according to their capacity to inhibit sperm agglutination and sperm immobilization (immune inhibition test) in human sera of sterile patients. Sperm-agglutinating and sperm-immobilizing activity was tested by the microtray agglutination and microtray immobilization test. A titer reduction was achieved only in sperm-immobilizing sera. Four sperm antigenic fractions revealed in the majority of the repeatedly tested sperm-immobilizing sera an inhibition of the antigen-antibody reaction. No reaction was observed after exhaustive absorption of the tested seven antigen fractions with sperm-agglutinating sera. Therefore the conclusion can be drawn that sperm-agglutinating and sperm-immobilizing antibodies react with different sperm antigens. Normal human sera without sperm antibodies served as control. As no sperm agglutination or sperm immobilization was obtained after absorption of these control sera our antigen fractions do not produce sperm agglutination or sperm immobilization.     

Activation of SPARC expression in reactive stroma associated with human epithelial ovarian cancer.

OBJECTIVE: SPARC (secreted protein, acidic, rich in cysteine) is a calcium-binding counteradhesive glycoprotein that has the potential to play an important role in promoting tumor progression and invasiveness. SPARC has been reported to be markedly down-regulated in ovarian carcinomas relative to the normal surface epithelium and has been suggested to act as a tumor suppressor in ovarian cancer. To more precisely define potential changes in SPARC expression associated with malignant transformation of the ovary, we compared the distribution of SPARC mRNA and protein expression in patient specimens of malignant and nonmalignant ovaries. METHOD: SPARC mRNA and protein expression was examined in 24 human invasive ovarian cancers, 5 tumors of low malignant potential (LMP), and 8 nonmalignant ovaries by in situ hybridization and immunohistochemistry. RESULTS: In nonmalignant ovaries, SPARC mRNA expression was restricted to thecal and granulosa cells of vessiculated follicles. Cytoplasmic SPARC immunoreactivity was observed in these compartments, whereas variable SPARC immunostaining was observed in normal surface epithelial cells. In contrast, high-level expression of SPARC mRNA and protein was detected in stroma of ovaries containing malignant tumor cells, particularly at the tumor-stromal interface of the invading tumors. Lower levels and a more diffuse pattern of SPARC mRNA expression were associated with LMP specimens. SPARC mRNA was not expressed by ovarian adenocarcinoma or by surface epithelial cells. Consistent with the in situ hybridization data, SPARC immunoreactivity was found throughout the reactive stroma of specimens containing ovarian carcinoma. However, despite the lack of detectable SPARC mRNA, SPARC immunoreactivity was consistently observed within the cytoplasm of cancer cells. CONCLUSION: The pattern of SPARC expression shown in this study indicates that SPARC is up-regulated in reactive stroma associated with invasive ovarian cancer. Moreover, these results raise the possibility that SPARC secreted from the stroma is internalized by ovarian cancer cells and may exert important intracellular effects upon these cells.     

荷人卵巢上皮癌裸鼠冻融卵巢组织移植的效果评价

目的:获取人卵巢上皮癌裸鼠原位移植瘤癌旁正常卵巢组织,经安全筛查并冻融后移植至去势裸鼠体内,探讨移植后效果,为临床应用提供依据。方法:将人卵巢上皮癌OVCAR3细胞种植于裸鼠皮下以获取瘤源,并进行卵巢原位移植,建立卵巢癌原位移植瘤模型,解剖裸鼠获取癌旁正常卵巢组织。癌旁组:取筛选后的癌旁卵巢组织进行玻璃化冷冻,复苏后分别进行皮下及原位移植,各20例;对照组:同龄正常裸鼠卵巢组织,皮下移植及原位移植各20例;去势裸鼠组:20只同龄去势裸鼠;正常卵巢组:20只同龄正常裸鼠。移植12周后,分析各组裸鼠卵巢组织内卵泡形态及激素分泌功能。结果:40只人卵巢上皮癌裸鼠原位移植瘤模型中共获取35份活检正常的癌旁卵巢组织,获取率87.5%(35/40)。玻璃化冷冻前后卵巢组织中卵泡形态及各级卵泡比例均无显著差异(P>0.05),癌旁冷冻组织和癌旁新鲜组织的异常卵泡比例差异无统计学意义(P>0.05),冷冻组织以初级卵泡及次级卵泡等窦前卵泡为主。癌旁组皮下移植组织存活率80%(16/20),对照组皮下移植组织存活率90%(18/20),癌旁组原位移植组织存活率90%(18/20),对照组原位移植组织存活率95%(19/20)。移植后组织内卵泡以次级卵泡及窦状卵泡为主,各级卵泡的形态及构成比和未移植的同龄正常裸鼠卵巢相似(P>0.05);癌旁组卵泡数明显低于对照组(P<0.05)及正常卵巢组(P<0.01);皮下移植和原位移植组织内的各级卵泡数差异无统计学意义(P>0.05)。癌旁组卵泡刺激素水平明显低于去势裸鼠组,而雌二醇水平明显高于去势裸鼠组(P<0.01);癌旁组卵泡刺激素水平明显高于对照组(P<0.05)及正常卵巢组(P<0.01),而雌二醇水平明显低于对照组(P<0.05)及正常卵巢组(P<0.01);皮下移植和原位移植的卵泡刺激素水平和雌二醇水平差异无统计学意义(P>0.05)。结论:癌旁卵巢组织冻融移植后有正常卵泡发育及激素分泌功能;皮下移植和原位移植均可取得较好的效果;癌旁卵巢组织冻融移植有望作为卵巢上皮癌患者治疗后恢复卵巢内分泌功能的有效手段。     

HER-2/neu及细胞角蛋白在卵巢上皮性肿瘤原发灶和转移灶中表达的检测及临床意义的研究

目的：了解卵巢上皮性肿瘤原发灶和转移灶中癌基因ＨＥＲ－２／ｎｅｕ和细胞角蛋白表达状况及其临床意义。方法：用免疫组化法检测卵巢上皮肿瘤原发灶６９份及转移灶３８份（５１处）标本中ＨＥＲ－２／ｎｅｕ和细胞角蛋白的表达，并与术后组织学分级及患者生存期分析相结合。结果：原发灶中二者阳性表达率与术后患者生存期无相关性（Ｐ＞０．０５）。角蛋白与组织学分级有关（Ｐ＜０．０５），而且在转移灶癌细胞中表达较稳定。在转移灶中ＨＥＲ－２／ｎｅｕ的表达明显低于原发灶中者（Ｐ＜０．０５），在原发灶和转移灶中都呈阳性表达的患者预后较差（Ｐ＜０．０５）。结论：在卵巢上皮性肿瘤原发灶和转移灶中ＨＥＲ－２／ｎｅｕ的表达有显著差别，其原因有待进一步研究。原发灶和转移灶中ＨＥＲ－２／ｎｅｕ都表达的患者提示预后不良。角蛋白与卵巢上皮性肿瘤分化程度有关，在转移灶中表达较稳定     

Photodynamic therapy of human ovarian epithelial carcinoma, OVCAR-3, heterotransplanted in the nude mouse.

OBJECTIVE: Our objective was to develop an animal model for the study of photodynamic therapy in the treatment of human ovarian epithelial carcinoma. STUDY DESIGN: The human ovarian carcinoma OVCAR-3 was heterotransplanted into nude, athymic mice and treated with photodynamic therapy consisting of the hematoporphyrin derivative Photofrin II 10 ng/kg and argon-pumped dye laser light at 630 nm (200 J/cm2). Growth of tumors on one side of seven mice (treated tumors, n = 7) was compared with contralateral tumors (control tumors, n = 8) not exposed to laser. Hematoporphyrin derivative uptake was determined in tumor and other tissues. RESULTS: Photodynamically treated tumors were completely ablated, and all remained absent. Hematoporphyrin derivative uptake was nonselective for tumor compared with other tissues. CONCLUSION: This model provides reproducible parameters for the study of photodynamic therapy in the treatment of gynecologic malignancies and demonstrates the need for methods to increase selective uptake of hematoporphyrin derivatives.