卵巢肿瘤患者血清微量元素与CA125关系的研究

联合测定１９例卵巢良性肿瘤、１７例卵巢恶性肿瘤及２１例健康妇女血清ＣＡ１２５及微量元素。结果发现肿瘤患者血清Ｃｒ、Ｆｅ水平较对照组明显降低，Ｃｕ、Ｚｎ和ＣＡ１２５水平明显升高；良、恶性肿瘤间无差异。恶性肿瘤患者Ｃｒ和ＣＡ１２５异常率高于良性肿瘤，两者的Ｃｕ、Ｚｎ和Ｃｕ／Ｚｎ比值异常率相近。表明联合测定ＣＡ１２５及Ｃｒ有助于卵巢恶性肿瘤的早期诊断。     

肿瘤标志物在卵巢癌早期诊断中的应用进展

卵巢癌（ovarian carcinoma）是女性生殖道常见的恶性肿瘤之一,尽管其发病率在女性生殖系统肿瘤中居第3位,死亡率却居第1位[1]。不同期别卵巢癌预后差异很大,早期卵巢癌患者通过手术和化疗其5年生存率可在90%以上,但目前能在早期获得诊断的患者不足25%。因此,早期诊断对提高卵巢癌患者生存率尤为重要。CA125是目前公认的卵巢癌术前诊断、疗效观察、术后复发和预后评估最具价值的观测指标,但CA125的合成受许多因素影响,如子宫内膜异位症,盆腔炎症等均可见CA125不同程度地升高,有研究发现40%～50%的Ⅰ～Ⅱ期卵巢癌患者的血清CA125检测值并不升高[2],     

卵巢癌规范性治疗中的若干问题

卵巢癌是女性生殖道恶性肿瘤致死率最高的肿瘤,我国目前发病率为8.14/10万,死亡率为3.13/10万[1]。由于缺乏有效的早期诊断方法,70%的患者在首次就诊时已是晚期,治疗存在相当难度。因此早期诊断和规范性治疗已成为卵巢癌诊治中最重要的问题。     

血清肿瘤标志物诊断早期卵巢癌的相关研究进展

卵巢癌是女性生殖道常见的恶性肿瘤之一。近年来,卵巢癌的诊疗技术得到了明显的提高,但卵巢癌的5年生存率未见明显改善。究其原因,主要与卵巢癌难以在早期发现有关。因此,寻找有效的卵巢癌早期检测手段,尤其是血清肿瘤标志物,对改善卵巢癌预后具有重要的意义。早期卵巢癌血清肿瘤标志物的研究一直是卵巢癌研究的热点之一,并取得了一定进展。     

血清CA125、CA199、CA153在卵巢浆、粘液性囊腺癌诊断和动态观察中的价值

目的：探讨血清中ＣＡ１２５、ＣＡ１９９、ＣＡ１５３对卵巢癌浆、粘液性囊腺癌的诊断和动态观察中的价值。方法：采用微粒子酶免疫测定法，于术前对４５例卵巢浆、粘液性囊腺癌和２３例附件良性疾病患者血清中的ＣＡ１２５、ＣＡ１９９、ＣＡ１５３水平进行测定，以观察其在诊断上的敏感性和特异性。对１８例卵巢浆液囊腺癌和１５例粘液囊腺癌行上述三种抗原作治疗中的动态观察，以探讨其价值。结果：此三项指标对浆、粘液卵巢癌诊断的敏感性和特异性，ＣＡ１２５分别为７３．３％和５０．０％；ＣＡ１９９为４２．２％和７７．３％；ＣＡ１５３为１５．６％和９０．９％。卵巢癌液囊腺癌ＣＡ１２５阳性率为１００％，明显高于粘液腺癌（Ｐ＜０．０１）；而卵巢粘液囊腺癌ＣＡ１９９阳性率为７８．３％明显高于浆液腺癌（Ｐ＜０．０１）；ＣＡ１５３在两癌中的阳性率分别为１３．６％及１７．４％，两者无差异性（Ｐ＞０．０５）。治疗中动态观察显示，ＣＡ１２５与ＣＡ１９９对卵巢浆、粘腺癌经满意手术和术后１～２疗程有效化疗后的患者，可降至正常；对术中有较大残留灶者两抗原值虽有下降，但常未能达正常；对复发患者，其值亦升高。结论：ＣＡ１２５和ＣＡ１９９均是卵巢浆、粘液囊腺癌诊断和监     

卵巢恶性肿瘤诊断与治疗指南(2021年版)

卵巢癌是严重威胁妇女健康的恶性肿瘤之一,发病率在女性生殖系统恶性肿瘤中位居第3位,病死率居妇科恶性肿瘤之首.卵巢癌发病隐匿,因目前尚缺乏有效的筛查及早期诊断措施,绝大多数患者在确诊时已存在局部或远处播散, 5年生存率约为46％.据其组织病理学特征,卵巢癌主要分为上皮性卵巢癌、生殖细胞肿瘤以及性索-间质肿瘤三大类.上皮性...     

线粒体DNA变异检测在卵巢癌临床诊治中的研究进展

卵巢癌发病率呈逐年上升趋势，死亡率位于女性生殖道恶性肿瘤之首。早期诊断是改善预后，提高长期生存率和生活质量的重要途径。但是，目前用于卵巢癌早期诊断及治疗监测的方法仍不能获得满意的效果。线粒体DNA（mitochondrial DNA，mtDNA）具有基因组小、突变率高、拷贝数高等特点，且与肿瘤的发生发展关系密切，故检测mtDNA变异有望在卵巢癌中发挥重要作用。本文综述了近年来卵巢癌中mtDNA变异检测的进展，以及mtDNA作为生物标志物在卵巢癌早期诊断、鉴别诊断、肿瘤进展监测以及化疗药物耐药性分析等方面的作用。     

CA125检测在卵巢上皮癌诊治监测中的价值探讨

１９９１年１月～１９９５年５月首次入院治疗的原发性卵巢上皮癌患者１５０例，复发性卵巢上皮癌患者２６例，卵巢癌第二次剖腹探查术１５例（共１９１例）。对ＣＡ１２５在卵巢上皮癌中的诊治监测价值进行探讨。结果发现１５０例首次治疗的卵巢上皮癌中，１３０例血ＣＡ１２５＞３５ｕ／ｍｌ，敏感性为８７％，特异性为８０％。其中浆液性上皮癌敏感性最高为９６％。Ｉ、Ⅱ期血ＣＡ１２５值为２１０±１０１ｕ／ｍｌ，Ⅲ、Ⅳ期为３９０±１５０ｕ／ｍｌ，Ｉ、Ⅱ期与Ⅲ、Ⅳ期ＣＡ１２５值之间有显著性等异（ｐ＜０．０５）；２６例复发卵巢癌中２２例血ＣＡ１２５值＞３５ｕ／ｍｌ，敏感性为８５％。１５例二探病人中，４例ＣＡ１２５值二探均为阳性。１１例血ＣＡ１２５值正常者中，６例二探结果为阳性，５例为阴性。提示ＣＡ１２５是目前辅助诊断卵巢上皮癌特别是浆液性腺癌最敏感的肿瘤指标；ＣＡ１２５的动态观察对卵巢上皮癌的治疗选择及预后判断具有重要价值。ＣＡ１２５的检测对二探的选择可提供可靠依据。     

分子诊断标记物在卵巢癌中的研究现状及进展

卵巢癌是女性常见的肿瘤之一，致死率较高，而且发病率呈逐年上升的趋势［1-6］。卵巢的解剖学位置较为特殊，早期仅出现腹痛、胃消化不良等常见症状，缺少早期准确的预警，早期诊断困难。多数卵巢癌确诊时已达到晚期，患者5年生存率不足20％［7］。因此早诊断、早治疗是降低女性卵巢癌患者死亡率的关键［8］。分子诊断标记物在肿瘤的诊断、监测、预后等多方面均有重要的意义［9］。本综述的重点在于分析已经用于尚在研究的分子诊断标记物，以探索更好的早期诊断卵巢癌的方法。     

血清CA125水平监测上皮性卵巢癌临床复发的作用

目的：分析血清ＣＡ１２５对上皮性卵巢癌临床复发的监测作用。方法：应用放射免疫法测定血清ＣＡ１２５对经过治疗病情稳定,ＣＡ１２５降到正常的２８例上皮性卵巢患者,定期测定血清ＣＡ１２５水平及其他临床检查项目,直到临床诊断肿瘤复发,分析血清ＣＡ１２５水平与肿瘤复发的关系（以ＣＡ１２５〈３５Ｕ／ｍｌ为正常值）。结果：本组２８例患者中,血清ＣＡ１２５〉３５Ｕ／ｍｌ者１２例,阳性率为４２．９％;血清ＣＡ１２５     

Application of monoclonal antibody OC 125 in gynecological oncology

This study was undertaken to determine whether the measurement of CA125 could effect an early diagnosis and a method for monitoring the course of gynecologic tumors. CA 125 in serum of 195 patients, including 15 apparently healthy women; 39 benign gynecologic tumors; 2 borderline ovarian tumors; 139 malignancies were measured by CENTOCOR cancer antigen 125 kits. Diagnosis of all patients was confirmed by pathology. None of the healthy women; 10% of benign tumors; 78% of epithelial ovarian cancers; 31% of endometrial adenocarcinomas and one out of five adenocarcinoma of uterine cervix had CA 125 level over 65 U/ml. In addition, 23 cases of ovarian cancer were monitored serially up to 9 months. In more than 80% of these patients, CA 125 levels were correlated with the regression or progression of the disease. The significance of this assay for early diagnosis and monitoring the course of ovarian cancer is discussed. It is considered that CA 125 is a promising and useful antigenic marker for monitoring the course of ovarian cancers.     

Soluble epidermal growth factor receptor (sEGFR) [corrected] and cancer antigen 125 (CA125) as screening and diagnostic tests for epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.     

Ovarian cancer early detection by circulating CA125 in the context of anti‐CA125 autoantibody levels: Results from the EPIC cohort

CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non‐cases. Anti‐CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether these antibodies (1) can serve as early detection markers, providing evidence of an immune response to a developing tumor, and (2) modify the discriminatory capacity of CA125 by either masking CA125 levels (resulting in lower discrimination) or acting synergistically to improve discrimination between cases and non‐cases. We investigated these objectives using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to four matched controls. Circulating CA125 antigen and antibody levels were quantified using an electrochemiluminescence assay. Adjusted areas under the curve (aAUCs) by 2‐year lag‐time intervals were calculated using conditional logistic regression calibrated toward the absolute risk estimates from a pre‐existing epidemiological risk model as an offset‐variable. Anti‐CA125 levels alone did not discriminate cases from controls. For cases diagnosed <2 years after blood collection, discrimination by CA125 antigen was suggestively higher with higher anti‐CA125 levels (aAUC, highest antibody tertile: 0.84 [0.76–0.92]; lowest tertile: 0.76 [0.67–0.86]; p_het = 0.06). We provide the first evidence of potentially synergistic discrimination effects of CA125 and anti‐CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection.     

晚期卵巢癌化疗中CA125下降的临床意义

Objective: The aim of this study was to compare the serum CA125 regression in advanced ovarian carcinoma patients treated with paclitaxel/platinum (TP) and platinum/epirubicin/ifosfamide (PAC) during early chemotherapy.The relationship between survival and CA125 regression during first line chemotherapy was evaluated.Methods: This retrospective TP or PAC chemotherapy, respectively.Only epithelial ovarian cancers were included.CA125 half-life was calculated by mono-compartmental logarithmic regression.Every patient's nadir CA125 concentration was also studied.T-test was used in comparing CA125 half-life and nadir CA125 between two groups.Survival analyses for progression-free survival (PFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) models for all of the patients.Results: There was not significant difference in CA125 half-life and nadir CA125 concentration between two groups (P > 0.05).CA125 half-life and nadir CA125 concentration had a univariate prognostic value for PFS and OS (P < 0.0001) in all of the patients.However pre-chemotherapy CA125 and different chemotherapy agents were not prognostic factors for PFS and for OS (P > 0.05, for each).In Cox models, CA125 half-life (P = 0.0006), residual tumour (P < 0.0001), and nadir concentration (P = 0.0032) were significant prognostic factors for disease free survival (DFS).For OS, CA125 half-life (P = 0.0013), residual tumor (P < 0.0001), and nadir concentration (P = 0.0118) were also the significant prognostic factors.Conclusion: There isn't significant difference in serum CA125 regression between patients who are treated with PAC or PT during early chemotherapy.CA125 half-life and nadir CA125 concentration are independent prognostic factor in advanced ovarian cancer.     

Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer.     

Multiple biomarker panels for early detection of ovarian cancer

Ovarian cancer is the eighth most common cause of cancer mortality in women. It is diagnosed in more than 20,000 women in the USA each year and approximately 15,000 women die of the disease annually. The majority of patients are diagnosed with advanced-stage ovarian cancer, as this deadly disease causes minimal and nonspecific symptoms until late in the course of the disease. No standardized screening test exists to reliably detect ovarian cancer. Cancer antigen (CA)-125 is a protein antigen found at abnormally high levels in the blood of many women with ovarian cancer. Most healthy women have CA-125 levels of below 35 units/microl of blood serum. However, a number of noncancerous conditions can cause elevated CA 125 levels, and many women with early-stage ovarian cancer have normal CA-125 levels. Owing to these limitations, this test is not recommended for routine screening in women who are not at high risk or who do not have specific symptoms of the disease. Currently, many researchers are focusing on simultaneous examination of multiple markers to increase sensitivity of the screening test for early detection of ovarian cancer. Analysis of the current literature shows that combining several biomarkers dramatically improves sensitivity of CA-125 in ovarian cancer patients. This article provides a comprehensive overview of existing studies in the area of multimarker panel development for the early detection and monitoring of ovarian cancer. Our literature review demonstrates that a multimarker approach for the generation of a prototype assay for early detection of ovarian cancer has a great potential to lead to the development of a screening test for this disease.     

Significance of CA 125 antigen levels in patients with ovarian cancer

CA 125 antigen levels were measured in patients with ovarian cancer (54 cases) by the RIA method using a monoclonal antibody OC 125 and were examined as a marker for ovarian cancer. The upper normal limit of CA 125 of 35 U/ml was derived from the mean value (15.7 U/ml) + 2 SD (9.3 U/ml) of CA 125 in healthy controls. The mean value of CA 125 in patients with ovarian cancer (1160 +/- 1850 U/ml) was statistically (p less than 0.001) higher than those of healthy controls, benign ovarian tumors (28 +/- 20 U/ml) and cervical cancers (226 +/- 526 U/ml). Elevated CA 125 levels were also found in the early stages pregnancy and endometriosis, but these cases did not show such high CA 125 values as those of ovarian cancers. In addition, CA 125 levels were not affected by the menstrual cycle. Among ovarian malignancies, elevated CA 125 values were specifically demonstrated in serous cystadenocarcinoma (positivity 89%) and markedly low in mucinous cystadenocarcinoma (positivity 16%). No positive correlation of CA 125 values with clinical stage (FIGO) were found in any ovarian cancer patients. The rise or fall of CA 125 level was well correlated with the progression or regression observed in cancer patients with positive CA 125 levels. In conclusion, serum CA 125 determinations may be useful in patients with ovarian cancer (except for mucinous type) for diagnosis and for monitoring the results of treatment.     

晚期卵巢癌化疗中CA125 下降的临床意义

目的:比较晚期卵巢癌TP方案和PAC 方案化疗血清CA125 下降情况。评价化疗中CA125 下降情况对晚期卵巢癌生存预后的预测作用。方法:122 例和95例Ⅱc～Ⅳ期卵巢癌患者肿瘤细胞减灭术后分别采用TP和PAC 方案化疗。每一个疗程化疗前取静脉血免疫法测定血清CA125,计算CA125 半衰期使用单项分割Log 减低法。t 检验用于比较两治疗组间CA125 半衰期和CA125 最低值间差异,应用单因素（Kaplan-Meier）和多因素Cox 回归分析全部患者化疗中CA125 下降情况对无进展生存和总生存期的意义。结果:两化疗组间CA125 半衰期和最低值间无显著性差异。单变量分析全部患者CA125 半衰期和最低值是无进展生存和总生存期的预后指标,而不同化疗方案及化疗前CA125 水平不是预后指标。多变量分析结果显示:CA125 半衰期,残存病灶,CA125 最低值是无进展生存和总生存期的独立预后指标。结论:晚期卵巢癌应用TP和PAC 方案化疗CA125 下降无显著性差异;一线化疗中CA125 半衰期和最低值是晚期卵巢癌独立的预后因素。      

Does Human Epididymis Protein 4 (HE4) Have a Role in Prediction of Recurrent Epithelial Ovarian Cancer

Background: Despite the fact that ovarian cancer is the seventh most common cancer in women worldwide and the fth leading cause of cancer death, It is the most common cause of death due to reproductive cancers in Thailand where epithelial ovarian cancer (EOC) is commonly found. According to a Thai statistical analysis in 2010 by the Department of Medical Services, epithelial ovarian cancer was the sixth most common cancer in Thailand from 2001 to 2003.The incidence of 5.1 per 100,000 women per year. Human epididymis protein 4 (HE4) is a novo diagnostic tumor marker for EOC. The combination of HE4 and carcinoma antigen 125 (CA 125) is a tool for detecting epithelial ovarian cancer (EOC) better than using CA 125 alone. Therefore, the researcher is interested in HE4 does have a role to predict recurrent epithelial ovarian cancer. Materials and Methods: The patients who had complete response after diagnosed with epithelial ovarian cancer by pathology, FIGO stage 3 or more had been treated through surgery and chemotherapy at the Sunpasitthiprasong Hospital from June 2014 until March 2016. The patients were followed up every three months, using tumor marker (CA 125, HE4,Carcinoma antigen 19-9) together with other checkup methods, such as rectovaginal examination, CXR every year and other imaging as indication. Afterwards, the data was analyzed for the ability of HE4 to detect recurrence of epithelial ovarian cancer. Results: In 47 patients in this study follow-up for 22 months after complete response treatment from surgery and chemotherapy in epithelial ovarian cancer, 23 had recurrent disease and HE4 titer rising .The patients with recurrent epithelial ovarian cancer demonstrated high levels of both HE4 and CA125 with sensitivity of 91.3% and 52.7% respectively, speci city of 87.5% and 95.6% and positive predictive values of 87.5% and 85.7% . HE4 can predict recurrent epithelial ovarian cancer (p-value=0.02242). Comparing HE4 and CA125 in predicting recurrent epithelial ovarian cancer HE4 had more potential than CA125 (p-value =0.8314). Conclusions: The present study showed HE4 to have a role in predicting recurrent epithelial ovarian cancer and HE4 is potentially better than CA125 as a marker for this purpose.     

The ROC 'n' role of the multiplex assay for early detection of ovarian cancer

In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to assess response to chemotherapy, detect recurrence, and distinguish malignant from benign disease; however, this marker is elevated in only 50-60% of stage I ovarian cancers, making it inadequate for early detection of malignancy. In this Practice Point, we discuss Visintin et al.'s attempt to validate a novel multiplex assay that uses a panel of six serum biomarkers -- leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA125. The study included 362 healthy controls and 156 patients with newly diagnosed ovarian cancer. The final model yielded 95.3% sensitivity, 99.4% specificity, a positive predictive value of 99.3% and a negative predictive value of 99.2%. These results indicate potential utility of this assay for early detection of ovarian cancer, although further validation is needed in a sample set representative of the general population.