Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids.

Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids.     

Adenovirus-mediated gene transfer of placental growth factor to perivascular tissue induces angiogenesis via upregulation of the expression of endogenous vascular endothelial growth factor-A

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that binds specifically to VEGF receptor (VEGFR)-1. However, the mechanism of PlGF- and VEGFR-1-mediated angiogenesis has remained unclear and some in vitro studies suggest that VEGF-A/VEGFR-2 signaling may also play a role in PlGF-mediated angiogenesis. To clarify these issues we evaluated angiogenic responses in a well-characterized periadventitial angiogenesis model using adenovirus-mediated PlGF-2 (AdvPlGF-2) gene transfer. We also investigated the roles of VEGFR-1 and VEGFR-2 in PlGF-2-mediated angiogenesis. Using a periadventitial collar technique, AdvPlGF-2 (1 x 10(9) plaque-forming units/ml) was transferred to the adventitia of New Zealand White rabbits alone or together with adenoviruses encoding soluble VEGFR-1 (sVEGFR-1) or soluble VEGFR-2 (sVEGFR-2). Adenoviruses encoding LacZ were used as controls. All animals were killed 7 days after gene transfer. Increased neo-vessel formation, upregulation of endogenous VEGF-A expression, and a significant inflammatory response were seen in AdvPlGF-2-transduced arteries. The neo-vessels were large and well perfused. sVEGFR-1 and sVEGFR-2 suppressed the angiogenic response of PlGF-2 by 80 and 71.7%, respectively. We conclude that adenovirus-mediated PlGF-2 gene transfer to vascular tissue increases endogenous VEGF-A expression and produces significant angiogenesis. Both sVEGFR-1 and sVEGFR-2 can inhibit PlGF-2-mediated angiogenesis. PlGF-2 is a potentially useful candidate for the induction of therapeutic angiogenesis in vivo.     

Functional significance of vascular endothelial growth factor and its receptor (receptor-1) in various lung cancer types

OBJECTIVES: VEGF is one of the key factors in tumor angiogenesis that may be involved in tumor growth and metastasis. VEGF receptor, a naturally occurring soluble form of the VEGFR-1 (sVEGFR-1. flt-1), is produced by endothelial cells by differential splicing of the flt-1 gene, and is a negative counterpart of the VEGF signaling pathway. DESIGN AND METHODS: We investigated the levels of VEGF and sVEGFR-1, a known intrinsic inhibitor of VEGF, in 42 patients with various types of lung cancers before beginning treatment and 18 healthy subjects. RESULTS: Serum sVEGFR-1 levels (mean +/- SD; pg/ml) were 465.17 +/- 158.34 in patients and were significantly higher than those of the healthy subjects (156.39 +/- 89.17) (P < 0.0001). Serum VEGF levels of patients (449.48 +/- 175.54 pg/ml) were significantly higher in patients than in healthy subjects (77.06 +/- 47.26 pg/ml) (P < 0.0001). CONCLUSIONS: We conclude that increased sVEGFR-1 and VEGF levels are important parameters in lung cancers.     

子宫内膜异位症患者VEGF、TNF-α和IL-6的表达及与R-AFS分期的相关性研究

目的探讨血管内皮生长因子(VEGF)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)在子宫内膜异位症患者血清和腹腔液中的表达及与病情发展的关系。方法选取2012年9月至2013年5月期间收治子宫内膜异位症患者80例作为实验组,并选同期在本院住院非子宫内膜异位症患者80例作为对照组。采用酶联免疫分析法测定两组患者血清和腹腔液中VEGF、TNF-α、IL-6的含量,并用相应的统计学方法对两组进行比较。结果 1子宫内膜异位症组血清及腹腔液中VEGF、TNF-α、IL-6含量均高于对照组,差异有统计学意义(P0.05);2子宫内膜异位症患者R-AFS临床分期各期血清及腹腔液中VEGF、TNF-α、IL-6含量有显著差异,并存在明显的正相关关系,差异有统计学意义(P0.05)。结论 1VEGF、TNF-α、IL-6在子宫内膜异位症发生发展过程中可能起协助作用;2血清及腹腔液中VEGF、TNF-α、IL-6含量可以作为子宫内膜异位症诊断及疾病严重程度判断的辅助指标。     

Role of transvaginal sonography in the detection of endometriomata

Endometriosis is a common cause of pelvic pain and infertility in young women. Transvaginal sonography is major means for diagnosing ovarian masses. In our study, we scanned 60 patients with endometriomata who underwent laparotomy or laparoscopy. We compared preoperative ultrasonographic diagnosis with histological reports. The sonographic criteria for the diagnosis of endometriomata were (1) cystic structure with low, homogeneous echogenicity and (2) thick cystic wall with regular margins. In 50 patients, sonography suggested an endometrioma. In 47 cases, the diagnosis was correct. The false-positive cases were all caused by cystic teratomas with a homogeneous sonographic pattern. Ten false-negative cases were diagnosed by ultrasonography as functional ovarian cysts (5), teratomas (3), and benign ovarian cystoma (1). Only 1 case of a 5-mm endometrioma was demonstrated by laparoscopy but not by TVS. The sensitivity of TVS for diagnosing endometriomata was 82.4% and specificity 97.7%; the positive and negative predictive values were 94% and 92.8%, respectively. The diagnostic accuracy of TVS was 93%. In our experience, TVS is a very specific means for diagnosing endometriomata when the typical pattern is detected; however, the sensitivity of the technique needs to be improved. © 1995 John Wiley & Sons, Inc.     

促红细胞生成素在子宫内膜异位症中的表达及意义

【目的】探讨促红细胞生成素（EP0）在子宫内膜异位症（简称内异症）中的表达及意义。【方法】选择34例内畀症患者（I～Ⅱ期12例,Ⅲ～Ⅳ期22例）和30例非内异症患者,采用双抗体夹心酶联免疫分析方法检测其血清及腹腔液中EPO的表达,分析内异症患者血清及腹腔液中EP0的相关性。【结果】①内异症组血清及腹腔液中EPO的表达显著高于对照组（P〈o．05）;②I～Ⅱ期内异症患者血清及腹腔液中EPO的表达与Ⅲ～Ⅳ期患者相比无显著性差异（P〉O．05）;③内异症组EPO在血清中表达与腹腔液中的表达成正相关。【结论】内异症患者血液及腹腔液中EPO过度表达,提示其可能是内异症发病机制中的重要一环,为内异症治疗提供新的思路。     

Treatment of malignant pleural effusion in non-small cell lung cancer with VEGF-directed therapy

BackgroundVascular endothelial growth factor (VEGF) is a critical regulator of malignant pleural effusion (MPE) in non-small-cell lung cancer (NSCLC). Bevacizumab (BEV) and apatinib (APA) are novel VEGF blockers that inhibit lung cancer cell proliferation and the development of pleural effusion.MethodsIn this study, we established Lewis lung cancer (LLC) xenograft mouse models to compare the therapeutic effect of APA and BEV in combination with cisplatin (CDDP) against MPE. The anti-tumour and anti-angiogenic effects of this combination therapy were evaluated by ¹⁸F-FDG PET/CT imaging, TUNEL assay and Immunohistochemistry.ResultsThe triple drug combination significantly prolonged the overall survival of the tumour-bearing mice by reducing MPE and glucose metabolism and was more effective in lowering VEGF/soluble VEGFR-2 levels in the serum and pleural exudates compared to either of the monotherapies. Furthermore, CDDP + APA + BEV promoted in vivo apoptosis and decreased microvessel density.ConclusionsMechanistically, LLC-induced MPE was inhibited by targeting the VEGF-MEK/ERK pathways. Further studies are needed to establish the synergistic therapeutic effect of these drugs in NSCLC patients with MPE.

KEY MESSAGES

• Combined treatment of MPE with apatinib, bevacizumab and cisplatin can prolong the survival time of mice, reduce the content of MPE, decrease the SUV_max of thoracic tumour tissue, down-regulate the content of VEGF and sVEGFR-2 in serum and pleural fluid, and promote the apoptosis of tumour cells. Angiogenesis and MPE formation can be inhibited by down-regulation of HIF-1α, VEGF, VEGFR-2, MEK1 and MMP-2 molecular signalling pathway proteins.

     

Serum levels of vascular endothelial growth factor and its receptors in patients with severe autism

Objective:To study vascular endothelial growth factor (VEGF) and its soluble receptors sVEGFR-1 and -2 in autism.Design and methods:We measured serum levels of angiogenic molecules in 22 patients with severe autism and 28 controls.Results:Patients and controls had similar sVEGFR-2 levels, but VEGF levels were lower and sVEGFR-1 higher in patients with autism.Conclusion:The imbalance between VEGF and its receptor sVEGFR-1 may be involved in the pathophysiology of autism.     

HE4、CA125及CA72-4在子宫内膜异位症及卵巢癌中的诊断差异研究

目的 寻找互补的生物标记物来帮助鉴别诊断子宫内膜异位症或其他卵巢良性肿瘤与卵巢癌.方法 收集50例健康女性、17例良性卵巢肿瘤、57例子宫内膜异位症及39例卵巢癌患者的血液样本,并分析血清中的CA125、HE4及CA72-4的含量.结果 血清CA125含量在子宫内膜异位症及卵巢癌患者血清中升高,但在其他卵巢良性肿瘤未见明显变化.HE4仅在卵巢癌患者血清中显著升高（P＜0.05）,在子宫内膜异位症及卵巢良性肿瘤患者中未增加.此外,CA72 4在66.7％的卵巢癌患者血清中上升,与子宫内膜异位症相比,也有显著统计学意义（P＜0.05）.结论 在血清CA125水平较高的女性中,通过检测HE4及CA72-4水平可帮助鉴别诊断子宫内膜异位症与卵巢癌.     

Suppression of lymphangiogenesis by soluble vascular endothelial growth factor receptor-2 in a mouse lung cancer model

The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2 into lung cancer cells and evaluated the influence on tumor progression and on genes regulating lymphatic formation and metastasis in vivo. A retroviral vector was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC), which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture supernatant by these cells were detected by western blotting using specific antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC-sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14 days after injection, immunohistochemistry was performed using an antibody directed against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were directly inoculated into the left lung in C57BL/6 mice and the number of micro-metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant. There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2 into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2 group compared with the control group. Furthermore, there were fewer micro-metastases in the pulmonary lymph nodes of the LLC-sVEGFR-2 group compared with the control group after cells were directly inoculated into the lung. These findings indicate that introduction of sVEGFR-2 suppressed lymphangiogenesis in primary lung cancer and also suppressed lymphogenic metastasis by inhibiting VEGF-C, followed by down-regulation of VEGFR-2, VEGFR-3 and MMPs. Accordingly, sVEGFR-2 might be a promising target for treatment of cancer by regulating lymphangiogenesis and lymphogenic metastasis.     

子宫内膜异位症腹水内血管内皮细胞生长因子及白介素8的测定

目的 :探讨子宫内膜异位症 (内异症 )患者腹腔液中血管内皮细胞生长因子 (VEGF)及白细胞介素 8(IL - 8)在内异症发病中的作用。方法 :采用双抗体夹心酶联免疫吸附法 (ELISA)检测 2 5例内异症患者 (Ⅰ、Ⅱ期 13例 ,Ⅲ、Ⅳ期 12例 ) ,15例非内异症患者 (对照 )腹腔液中VEGF及IL - 8的含量 ,分析VEGF、IL - 8的浓度及其与内异症分期 [美国生殖协会修正标准分期 (R -AFS) ]的相关性。结果 :内异症患者腹腔液中VEGF及IL - 8的浓度明显高于对照组 ( P <0 0 5及 P <0 0 1) ,VEGF及IL - 8与R -AFS分期无相关 ,VEGF与IL - 8之间无明显相关。结论 :内异症患者腹水中VEGF、IL - 8的水平升高是腹腔微环境改变导致内异症的可能及部分原因     

电视腹腔镜保守性手术治疗卵巢子宫内膜异位囊肿的价值

目的：评价电视盆膜镜下保守手术治疗卵巢子宫内膜异位囊肿的价值及探讨式的选择。方法：对30例卵巢子宫内膜异位囊肿患者在电视腹腔镜下行保守手术临床分析。结果：21例行卵巢囊肿剥除电凝缝合术，9例行卵巢囊肿穿刺缝合术，其中10例同时行粘连松解术。症状缓解有效率为85．7％，受孕率为42％，囊肿治疗率为93．3％。结论：电视腹腔镜下保守性手术治疗卵巢子宫内膜异位囊肿创伤小、恢复快、并发症少，但不能提高症状缓解有效率及受孕率；镜下术式选择卵巢子宫内膜异位囊肿直径大于3cm者以囊肿剥除电凝缝合整形术为主，异位囊肿直径小于3cm者以囊肿穿刺电凝术为好。     

Activity of eosinophils and immunoglobulin E concentration in the peritoneal fluid of women with endometriosis.

Autoinflammatory phenomena, including autoantibody production and atopy, have been regarded as associated with endometriosis. The present study investigates the activity of eosinophils and the distribution of immunoglobulin E concentrations in the peritoneal fluid of women with early endometriosis. The study group consisted of 30 patients with laparoscopically diagnosed early endometriosis. The healthy control group consisted of 18 females with no evident changes in the abdominal cavity and no endometrial foci. Concentrations of immunoglobulin E in serum and peritoneal blood were determined by enzyme immunoassay. The activity of eosinophils was estimated according to the expression of the early activation molecule CD69 by the flow cytometry method. The concentrations of immunoglobulin E in the peripheral blood and peritoneal fluid were similar in both groups. However, the count of CD69+ eosinophils was higher in the peritoneal fluid of women with endometriosis. The results indicate that activated eosinophils accumulate in the peritoneal fluid in early endometriosis and can play a significant role in the pathogenesis of the disease.     

Vascular endothelial growth factor in thyroid cyst fluids

BACKGROUND: The pathogenesis of cystic thyroid nodules is incompletely understood. Based on the assumption that vascular endothelial growth factor (VEGF) may play an important role in the pathogenesis of thyroid cyst fluid, we investigated the VEGF concentration in cyst fluids of thyroid lesions. DESIGN: Cyst fluids from 24 patients (age 31-84 years) were obtained using ultrasound-guided fine-needle aspiration. The patients' cystic thyroid nodules were of different origins. METHODS: Thyroid and cyst volumes were determined using high-resolution ultrasonography. VEGF concentrations were determined using a solid-phase enzyme-linked immunosorbent assay (ELISA). RESULTS: Differing elevated VEGF concentrations were demonstrated in cyst fluids of thyroid nodules of varied origins. The VEGF concentration in cyst fluid of patients with adenomatous goiter was significantly higher (P < 0.05) than that in thyroid nodules with cystic degeneration. The highest level of VEGF was found in bloody cyst fluid when compared with levels in other cyst fluids (P < 0.05). Interestingly, there was significant correlation (P < 0.01) between thyroid volume and VEGF concentration in cyst fluid, but no significant correlation (P = 0.20) between cyst volume and VEGF concentration. CONCLUSION: Significantly increased VEGF concentrations were found in bloody cyst fluid and in cyst fluid of thyroid adenomatous goiter, compared with VEGF concentrations in degenerative thyroid cysts. Our results suggest that VEGF may play an important role in the pathogenesis of thyroid cyst fluid.     

Comparison of endovaginal ultrasound and cytological evaluation of cystic ovarian tumors

Endovaginal ultrasound is a good diagnostic tool for distinguishing between cystic and solid tumors. Unilocular cysts in the lower pelvis seem to carry a very low risk of malignancy in women of all ages. Cytological evaluation of the fluid from a cystic ovarian tumor has rather poor accuracy in diagnosing malignancy. For such a reason, this study compares the diagnostic accuracy of endovaginal ultrasound to that of cytology of the cyst content. Furthermore, we wanted to determine whether irrigation after puncture of a cystic tumor could increase the number of cells in the fluid and thereby increase the diagnostic accuracy of the cytological evaluation. Fifty women admitted to surgery due to a cystic tumor were endovaginally scanned the day before surgery. After the intact tumor had been removed from the abdomen, its contents were aspirated by means of a double-channelled needle. Irrigation was performed with Ringer acetate. Cytological evaluation was performed on both portions of the cyst fluid. The negative predictive value with respect to malignancy was 77% for cytology of the first portion of the aspirate, 81% for irrigation, and 100% for ultrasound. The corresponding figures for positive predictive value were 100%, 100%, and 73%. We conclude that cytological evaluation after irrigation of a cystic ovarian tumor does not significantly increase accuracy in diagnosing malignancy compared to endovaginal ultrasound.     

子宫内膜异位症患者外周血及腹腔液中sICAM-1的检测及意义

目的:检测子宫内膜异位症患者外周血及腹腔液中可溶性细胞粘附分子-1(sICAM-1)的水平,并进一步探讨它们在子宫内膜异位症免疫发病机制中的作用。方法:应用酶联免疫吸附法(ELASA)检测了子宫内膜异位症患者和正常对照组妇女外周血及腹腔液中的sICAM-1的水平。结果:sICAM-1在子宫内膜异位症患者外周血及腹腔液中的水平均高于正常对照组,有显著性差异(P<0.05);重度子宫内膜异位症患者血清中的sICAM-1高于轻度患者,有显著性差异(P<0.05);重度子宫内膜异位症患者腹腔液中的sI-CAM-1水平高于轻度患者,但无显著性差异(P>0.05)。结论:sICAM-1在子宫内膜异位症患者外周血及腹腔液中的水平升高。这些异常变化导致子宫内膜异位症患者腹腔局部免疫微环境发生改变,促进了子宫内膜异位症的发生发展。     

Antiangiogenic Gene Therapy With Soluble VEGFR-1, -2, and -3 Reduces the Growth of Solid Human Ovarian Carcinoma in Mice

We studied antiangiogenic and antilymphangiogenic effects of sVEGFR-1 (sFlt-1), sVEGFR-2 (sFlk-1/KDR), and sVEGFR-3 (sFlt-4) gene transfers and their combinations in intraperitoneal ovarian cancer xenograft mice (Balb/c-Anu, n = 55). Gene therapy was initiated when the presence of sizable tumors was confirmed in magnetic resonance imaging (MRI). Adenovirus-mediated gene transfer was performed intravenously via tail vein as follows: AdLacZ as a control (group I), AdsFlt-1 (group II), AdsKDR (group III), AdsFlt-4 (group IV) and two combination groups of AdsFlt-1 and AdsFlt-4 (group V) and AdsFlt-1, AdsKDR, and AdsFlt-4 (group VI). Antitumor effectiveness was assessed by sequential MRI, immunohistochemistry, microvessel density, overall tumor growth, and survival time. In combination group VI, intraperitoneal tumors were significantly smaller than in the control group at the end of the follow-up (P < 0.001). Furthermore, in group VI the microvessel density (microvessels/mm²) in tumor tissue and the total area of tumors covered by microvessels were significantly smaller than in the controls. One mouse in group V was cured. The combined antiangiogenic gene therapy with soluble VEGFRs reduced tumor growth, tumor vascularity, and ascites formation in ovarian cancer xenografts. The results suggest that the combined antiangiogenic gene therapy is a potential approach for the treatment of ovarian cancer patients.     

IVF-ET中彩色多普勒超声及VEGF水平评价卵巢反应性的研究

目的研究IVF-ET中卵巢基质和卵泡周边的血供情况、体内VEGF水平与卵巢反应性之间的关系,探讨影响卵巢反应性的机制。方法42例行IVF-ET治疗的女性,长周期方案促排卵,根据检测侧卵巢内获取的卵母细胞数目分为低反应(1~3个)、正常反应(4~8个)和高反应卵巢组(8个以上),于hCG注射日采用经阴道彩色多普勒超声检测该侧卵巢基质内动脉的收缩期峰值血流速度(PSV)、舒张末期血流速度(EDV)、搏动指数(PI)、阻力指数(RI)、收缩期/舒张期流速比值(S/D),并对卵泡周边血流分布分级评分;ELISA法检测取卵日血清和卵泡液中VEGF浓度。结果低反应卵巢组卵巢基质内动脉的PSV、EDV、卵泡周边血流分布评分较正常和高反应卵巢组显著降低,PSV、EDV、卵泡周血流分布评分与获取的卵母细胞数量具有正相关关系;所有研究对象卵泡液VEGF水平显著高于血清VEGF水平,低反应卵巢组卵泡液VEGF水平显著高于正常反应和高反应卵巢组,卵泡液VEGF水平与获取的卵母细胞数量呈负相关关系。结论卵巢基质内血流的PSV、EDV和卵泡周血流分布、卵泡液VEGF水平与卵巢的反应性密切相关,卵巢基质内血流速度升高、卵泡周边血流丰富,有助于提高卵巢的反应性;低反应卵巢组卵泡液VEGF水平显著升高,推测是由于其卵巢基质内血流速度低,卵泡周血管分布少,导致VEGF代偿性分泌增加。     

Laboratory testing for endometriosis

Background: Typically, endometriosis is diagnosed surgically by laparoscopy. CA-125 is the principal serum marker used in the diagnosis and management of late-stage endometriosis. The search for a body fluid marker of early stage disease has included studies of serum, peritoneal fluid (PF), and/or tissue levels of secretory proteins, cell adhesion molecules, cytokines, tumor necrosis and vascular endothelial growth factors (VEGFs), chemokines, antiendometrial antibodies, autoantibodies to oxidized lipoproteins, aromatase P-450 expression, cytokeratins, and hormone receptors. We compared the diagnostic accuracy and clinical utility of these various types of substances in the non-surgical identification of patients with endometriosis. Method: We reviewed the MEDLINE database for all publications on serum, peritoneal fluid and tissue markers of endometriosis. Results: Except for serum interleukin (IL)-6 and peritoneal fluid tumor necrosis factor (TNF)- levels, the diagnostic accuracy of other markers of endometriosis was either similar or worse than that of CA-125 (sensitivity 24–94%; specificity 83–93%). The diagnostic accuracy of IL-6 and TNF- was 90–100% (sensitivity) and 67–89% (specificity). Conclusion: CA-125 has limited diagnostic accuracy in the identification of early stage endometriosis and none of the other markers we reviewed dramatically outperformed CA-125 in this regard with the possible exception of serum IL-6 and peritoneal fluid TNF- levels.     

Measurement of human chorionic gonadotropin-related immunoreactivity in serum, ascites and tumour cysts of patients with gynaecologic malignancies

Abstract. Human chorionic gonadotropin (hCG)-like molecules have been reported to be elevated in a substantial fraction of serum samples from patients with various gynaecologic tumours and have been discussed as possible markers in these malignancies. Employing highly sensitive and specific immunoradio-metric assays, we determined total hCG-related immunoreactivity (hCG/hCGβ), as well as free α-subunit (α-SU), common to all glycoprotein hormones, in serum ( n = 106) and malignant effusions ( n = 26) of women with gynaecologic malignancies. For comparison, we also measured hCG/hCGβ in nonmalignant ascitic fluids ( n = 21). HCG/hCG serum levels were elevated (>5 IU L^-1) in 39 of 106 patients (37%) with gynaecologic malignancies, whereas free α-SU was above normal range only in seven (6.6%). Frequencies of hCG/hCGβ elevations were similar in women with endometrial ( n = 39), cervical ( n = 40) and ovarian ( n = 27) cancer, being 30%, 35% and 41%, respectively. In malignant ascites ( n = 15) and tumour cyst fluids ( n = 11) of patients with ovarian cancer, hCG/ hCGβ concentrations were significantly higher than in the corresponding serum samples and benign ascitic samples. Free α-SU, on the other hand, was increased in only one of 26 malignant effusions. In conclusion, hCG/hCGβ is frequently elevated in serum of patients with endometrial, cervical and ovarian cancer and may serve as a tumour marker in these malignancies, particularly in patients where other markers are negative. In this respect, analysis of ascitic or tumour cyst fluids may be of higher diagnostic value as serum measurements.