CA 125 and vascular endothelial growth factor in the differential diagnosis of epithelial ovarian tumors

Tumor markers have been investigated in differentiation of benign and malignant tumors. We analyzed CA 125 and vascular endothelial growth factor (VEGF) levels in serum and cyst fluid in patients with epithelial ovarian tumors. Serum and tumor cyst fluid of 50 patients with ovarian epithelial tumors (7 malignant, 3 bordeline and 40 benign) were assayed for VEGF by ELISA and CA 125 levels by chemoluminescence. CA 125 serum levels were significantly higher in patients with malignant and borderline tumors than in patients with benign cysts (p = 0.0005). CA 125 cyst fluid contents were comparable for malignant, borderline and benign ovarian tumors (p = 0.39). Significantly higher levels of VEGF were present in cyst fluid for malignant and borderline tumors compared with benign cysts (p < 0.0001); however, serum levels of VEGF were similar among all patients (p = 0.25). The CA 125 serum levels correlated with matched VEGF cyst fluid levels (r = 0.44, p = 0.0015). Serum CA 125 and cystic VEGF were good methods to differentiate benign and malignant epithelial ovarian tumors. Patients with elevated intracystic VEGF levels presented significantly higher CA 125 serum levels, although the CA 125 intracystic content overlapped. The angiogenesis and enhancement of vascular permeability induced by VEGF represents a new hypothesis for the release of the CA 125 antigen into the circulation in patients with ovarian epithelial neoplasm.     

CA_(125)、CA_(19.9)、CEA在卵巢上皮性交界性肿瘤中的临床价值

目的 :探讨测定血清CA12 5、CA19.9、CEA在诊断卵巢上皮性交界性肿瘤中的临床价值。方法 :回顾分析卵巢交界性肿瘤 5 0例血清CA12 5、CA19.9、CEA水平与临床资料。结果 :浆液性及粘液性肿瘤中CA12 5的阳性率分别为 5 3.85 %和 60 % ,差异无显著性 (P >0 .0 5 ) ,临床分期晚者CA12 5阳性率有增高趋势 ;粘液性肿瘤中CA19.9的阳性率为 4 3.75 % ;CEA阳性率为 12 % ,仅见于粘液性或以粘液性为主的肿瘤中 ;与术前相比 ,术后CA12 5、CA19.9水平及阳性率均显著下降 (P <0 .0 5 )。结论 :CA12 5、CA19.9对卵巢上皮性交界性肿瘤的术前诊断及疗效监测有一定价值 ,CEA则在鉴别组织学类型中有一定价值。     

Serum levels of six tumor markers in patients with benign and malignant gynecological disease

Summary We studied the pretreatment serum levels of 6 tumor markers in gynecological patients with and without malignant disease. The tumor markers were carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), ferritin, Schwangerschaftsprotein 1 (SP₁), Schwangerschaftsprotein 3 (SP₃) and cancer antigen 125 (CA125). The results were as follows: (1) Serum CA125 and TPA levels were raised in 81% and 57% of patients with ovarian serous cystadenocarcinoma: CEA and SP₃, in 52% and 43% respectively of patients with ovarian mucinous cystadenocarcinoma; CA125, TPA and SP₃, in 76%, 48% and 48% respectively of patients with other ovarian malignancies; and TPA and SP₃, in 56% and 40% respectively of patients with endometrial carcinoma. (2) Serum levels of TPA, ferritin and CA125 were more often raised with advancing stages of malignant disease. (3) Serum TPA levels were elevated in 55% of patients with stage I endometrial carcinoma, and serum SP₃ levels were elevated in 35% of patients with a stage I malignant ovarian neoplasm and in 45% of patients with endometrial carcinoma. (4) One of the 6 tumor markers showed a raised level in 84% of patients with gynecologic malignancy as against 56% in those with benign gynecologic diseases.     

Relation between serum levels of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125) and their immunohistochemical identification in benign and malignant gynecological disease

Summary We studied immunohistochemical stains for TPA and CA125 in patients with benign and malignant gynecologic diseases. The results were as follows: (1) CA125 was not found in ovarian mucinous cystadenocarcinoma but was demonstrated immunohistochemically in 82% of ovarian serous cystadenocarcinomas and 83% of Krukenberg's tumors. (2) TPA was demonstrated in 65% of ovarian serous and 75% of ovarian mucinous cystadenocarcinomas, and in 58% of endometrial carcinomas. (3) TPA was found in all trophoblastic tumors examined, while CA125 was found in none. Eighty-three percent of patients with trophoblastic diseases had raised serum TPA levels. (4) When serum CA125 levels were raised, CA125 was demonstrated immunohistochemically in 71% of patients with ovarian serous cystadenocarcinomas, 67% of patients with Krukenberg's tumors and 100% of patients with tubal carcinomas. (5) Despite elevated serum levels, CA125 and TPA were not identified by immunohistochemistry in 64% cases of benign ovarian disease and in 80% of patients with uterine myomata. (6) It would seem that CA125 was more easily released from tumor cells than TPA.     

The effect of maternal age, parity, and fetal sex on the amniotic fluid and maternal serum levels of CA 125, CA 19.9, CA 15.3, and CEA

OBJECTIVE: To determine the effects of maternal age, parity and fetal sex on amniotic fluid (AF) and maternal serum (MS) levels of CA 125, CA 19.9, CA 15.3 and carcinoembryonic antigen (CEA). SUBJECTS AND SETTING: MS samples for CA 125, CA 19.9, CA 15.3 and CEA assay were obtained from 62 pregnant women at 16-20 weeks of gestation. AF was obtained from the same patients during genetic amniocentesis. METHODS: Radioimmuno assay to determine tumor marker concentrations. RESULTS: The following statistically significant differences were observed: (1) MS CA 19.9 and CA 15.3 values were elevated in the primigravida group. MS mean CA 19.9 value was also abnormally elevated. (2) MS mean CA 19.9 and CEA values and AF mean CA 19.9 value were elevated in the female fetus group. CONCLUSIONS: Parity and fetal sex were associated with AF and MS levels of some tumor markers. Therefore, to prevent misinterpretation of the tumor marker values during pregnancy further investigation is needed to find normal values for each trimester, paying particular attention to parity and fetal sex.     

Clinical evaluation of MRI in the diagnosis of borderline ovarian tumors

OBJECTIVE: To evaluate the clinical potential of contrast-enhanced MRI with Gd-DTPA (gadopentetate dimeglumine) in the diagnosis of borderline ovarian tumors. METHODS: Thirteen patients with 14 borderline ovarian tumors were evaluated with serum levels of four tumor markers (CA125, CA19-9, SLX and CEA) and contrast-enhanced MRI. RESULTS: Among the 13 patients, five had normal serum levels of all four tumor markers, and five had high serum levels of plural tumor markers. The positive rates of CA125, CA19-9, SLX, and CEA were 46.2% (6/13), 38.5% (5/13), 30.8% (4/13), and 7.7% (1/13), respectively. With contrast-enhanced MRI, all 13 patients were diagnosed as having malignant tumors using the widely accepted criteria of MRI findings for the diagnosis of malignant ovarian tumors. CONCLUSIONS: In the present study, all 14 borderline tumors had similar MRI findings to those of malignant tumors and were diagnosed as ovarian cancers with contrast-enhanced MRI, unrelated to the serum levels of tumor markers.     

The diagnostic value of multiple tumor markers in malignant ovarian neoplasms

Ovariancanceristhemostfrequentcauseofdeath fromgynecologicalcancer.Almost90%ofpatientsare diagnosedwithmetastaticdiseaseinthepelvisorabdo menandforthesepatients5yearsurvivalratesareless than30%.Incontrast,thesmallproportionofpatients diagnosedwithstageIovariancancerconfinedtotheo varieshavea5yearsurvivalrateinexcessof90%[1].Tumormarkerisakindofsubstancecorrelatedwiththe occurrenceoftumor.Itarisesfromthetumortissue,ex istsinthetumor,orexcretesintobloodorotherbody fluid[2].Nowadaysmorethan100ki…     

The diagnostic value of multiple tumor markers in malignant ovarian neoplasms

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.     

Ultrasonographic criteria and tumor marker assay are good procedures for the diagnosis of ovarian neoplasia in preselected outpatients

PURPOSE OF INVESTIGATION: To identify parameters for the diagnosis of ovarian neoplasia using ultrasonography (US) and serum tumor marker (TM: CA125, CA19.9, CA15.3, AFP, CEA and estradiol) assay. METHODS: Prospective study which included 373 women with increased ovarian volume (> 18 cm3 in premenopause and > 8 cm3 in postmenopause). US criteria (> or = 1) for surgery were: persistent (> 4 months) or increased cyst, cysts with > 1 thick septum or > or = 2 thin septa, cyst diameter > or = 7 cm, vegetation, calcification or cystic predominance (> 50%), solid tumor (> 50%). Doppler with a resistance index (RI) < 0.4 was considered abnormal. RESULTS: Laparotomy was performed in 164 (44%) patients with 66 (40.2%) benign neoplasias and 19 (11.6%) malignant cases (73.6% at Stage I or II). Two hundred and nine patients were maintained on clinical follow-up. The sensitivity for neoplasia and malignant neoplasia was, respectively, for RI: 17 and 63.6 and RI plus TM: 53.1 and 90.9. CONCLUSION: Ultrasound criteria and TM assay were indicated for the diagnosis of ovarian neoplasia.     

组织多肽抗原在卵巢癌诊断及监测中的应用

目的评价组织多肽抗原（ＴＰＡ）在卵巢癌诊断和监测中的临床价值。方法应用放射免疫方法测定了２４例正常妇女、２７例妇科良性疾患及６０例卵巢癌患者的血清ＴＰＡ及ＣＡ１２５值并进行比较分析。结果ＴＰＡ在卵巢上皮性癌患者中的异常检出率为８２％,ＣＡ１２５为７０％,二者总的异常检出率为９２％。在绝大多数正常妇女和卵巢良性肿瘤患者中,ＣＡ１２５和ＴＰＡ在正常范围。作为卵巢癌相关标志物,ＴＰＡ与ＣＡ１２５具有相似敏感性。１９例动态观察结果显示,ＴＰＡ和ＣＡ１２５二者与病情转归是一致的。结论ＴＰＡ和ＣＡ１２５联合应用对卵巢癌的鉴别诊断及提高总的异常检出率具有价值。     

Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.     

Is there a correlation between tumor marker panel and tumor size and histopathology in well staged patients with borderline ovarian tumors?

AIMS: To investigate whether there is a correlation between serum tumor markers panel (CA 125, CA 19-9, CA 15-3, and carcinoembryonic antigen (CEA)) and tumor size and histopathology in well staged patients with borderline ovarian tumors (BOTs). METHODS: Four tumor markers (CA 125, CA 19-9, CA 15-3, and CEA) were analysed clinically in 60 well staged patients with borderline ovarian tumor, for this retrospective observational study. RESULTS: Most patients had serous histology and early stage disease, and the mean age at the time of diagnosis was 40.70 years (range: 19-73). Twenty-nine patients (48.3%) had high CA 125 levels (>35 U/l), 15 patients (25%) had high levels of CEA (>4 ng/ml), 12 patients (20%) had high levels of CA 19-9 (>37 U/ml), and 9 patients (15%) had high levels of CA 15-3 (>30 ng/ml) at the time of initial surgery. The positive rate of CA 125, CA 19-9, CA 15-3, and CEA in serous tumor were 57.9, 7.9, 7.9 and 15.8%, respectively. These figures were 31.8, 40.9, 27.3 and 40.9% in mucinous tumor. The positive rate of CA 125 in the serous group was statistically significantly higher than that in the mucinous group, while the positive rates for CA 19-9 and CEA in mucinous histology was significantly higher than those in serous tumors. In case of grouping the tumor size as <4, 4.1-10 and >10 cm, the mean serum levels of tumor markers had significantly increased by increasing tumor size (p<0.05 for CA 125, and CA 19-9, p>0.05 for CA 15-3, and CEA). CONCLUSION: The high levels of tumor markers, especially for CA 125 and CA 19-9, may indicate the larger tumor size. The elevation of serum CA 125 may suggest serous tumors, while the high level of serum CA 19-9 and CEA may indicate mucinous BOTs.     

4种肿瘤标志物对上皮性卵巢癌定性诊断价值的初步研究

目的：探讨多胺（ＰＡ）、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９在定性诊断上皮性卵巢癌中的价值。方法：应用ＨＰ％Ｍ高效液相色谱仪和ＨＰ１０４０Ａ荧光检测器或酶联免疫吸附法测定上皮性卵巢癌４０例和卵巢良性肿瘤１８例血清中ＰＡ、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９水平。结果：４种标志物中，ＰＡ诊断卵巢癌的敏感性、阳性预测率、阴性预测率和预测准确率最高，其次是ＣＡ１２５。结论：ＰＡ对人类恶性肿瘤缺乏特异性，但可作为鉴别卵巢良、恶性病变的有价值标志物。联合测定ＰＡ和ＣＡ１２５时，其敏感率为９４．９％。因此，联合测定ＰＡ和ＣＡ１２５可作为筛查卵巢良、恶性肿瘤的方法。     

The comparison of CA-125 and CEA levels in serum and ovarian cyst fluid in girls and young women]

OBJECTIVES: The aim of the study was to compare the CA-125 and CEA levels in serum and ovarian cyst fluid. MATERIALS AND METHODS: Concentration of the CA-125 and CEA were measured at 12 girls and young women with benign, low malignant potential and functional cysts hospitalized in our teaching department. Concentrations were measured using immunoenzymatic method. RESULTS: We did not observe any difference in serum levels of CA-125 and CEA between neoplastic and functional cysts. On the contrary we found very high levels of the markers in the neoplastic cyst fluid in comparison with the functional ovarian cyst fluid. CONCLUSION: It seems that high levels of the CA-125 and CEA in neoplastic cyst fluid in comparison with functional may be useful in differential diagnosis.     

Clinical usefulness of sialyl SSEA-1 antigen as tumor marker for ovarian cancer as compared with CA125, CA19-9, TPA, IAP, CEA and ferritin

In order to determine the clinical significance of sialyl SSEA-1 antigen, we compared its usefulness as a tumor marker for ovarian cancer with simultaneously measured CA125, CA19-9, TPA, IAP, CEA and ferritin. The sialyl SSEA-1 antigen in serum was measured by radioimmunoassay with an "FH-6" Otsuka Kit. The immunohistochemical localization of sialyl SSEA-1 antigen in ovarian carcinoma tissues was determined by an immunoperoxidase method using FH-6 monoclonal antibody. Among fifty-one patients with ovarian cancer, the incidence of elevated serum levels was 54.9% with sialyl SSEA-1 antigen, 90.2% with CA125, 48.8% with CA19-9, 78.0% with TPA, 73.1% with IAP, 17.1% with CEA and 63.4% with ferritin. On the other hand, among the patients with uterine malignancies and gynecologic benign tumors, the incidence of elevated sialyl SSEA-1 antigen levels in serum was lower than that of other tumour markers. In the patients with ovarian cancer, the serum levels of sialyl SSEA-1 antigen increased in accordance with the advance of the clinical stage and were also correlated with the effect of therapy. In the examination of immunohistochemical localization of sialyl SSEA-1 antigen, a positive reaction occurred in 10 out of 30 ovarian carcinoma specimens. Intense staining appeared in the secretory materials, in the luminal surface of the glands, and in the cytoplasm of cells. Thus, sialyl SSEA-1 antigen appears to be a useful tumor marker for the diagnosis of ovarian cancer, especially when measured simultaneously with CA125, CA19-9, TPA, ferritin and IAP.     

The Chemotactic Cytokine Interleukin-8—A Cyst Fluid Marker for Malignant Epithelial Ovarian Cancer?

Due to the difficulties in separating malignant and benign ovarian cysts by transvaginal ultrasound and other techniques, there is a need for biochemical markers in serum or cyst fluids. In the present study we have evaluated the levels of the chemokine interleukin-8 (IL-8) in ovarian cysts. IL-8 is known to be expressed in the normal ovary and to influence proliferation and angiogenesis of several nonovarian types of tumors. Cyst fluids from benign (n= 15) and malignant (n= 13) ovarian tumors were analyzed. The levels of IL-8 were found to be significantly (13-fold) higher in cyst fluids from malignant tumors (18.1 ± 7.5 ng/ml; mean ± SE) compared to benign cysts (1.3 ± 0.7 ng/ml). The plasma levels of IL-8 were considerably lower (2.9 and 0.3% of levels in benign and malignant cyst fluids, respectively) than in cyst fluids. No difference in the plasma levels of patients with benign or malignant tumor could be detected. In contrast, the levels of CA 125 were significantly higher in plasma of patients with malignant disease with the inverse relation in cyst fluids. In conclusion, the levels of IL-8 are markedly elevated in cyst fluid from malignant tumors compared to benign. This specific increase indicates a role for this cytokine in ovarian tumor biology.     

Diagnostic efficacy of tumor markers, sonography, and intraoperative frozen section for ovarian tumors

Using sonography, we classified the adnexal masses of 292 patients into 4 patterns. Pattern A was benign cystic tumors; B was benign mixed tumors (cysts with a smooth solid component); C was malignant mixed tumors (cysts with an irregular solid component or thickened septum), and D was solid tumors. We diagnosed tumors showing patterns A and B as benign, while patterns C and D represented tumors with low malignant potential or actual malignancy. The sensitivity and specificity of sonography was 82.2 and 82.1%, respectively, and these values were superior to those for tumor markers (CA125, CA19-9, CA72-4). Both the sensitivity and specificity of intraoperative frozen sections were the highest, showing that this is the most reliable examination. However, 15 of 191 patients undergoing frozen section were upgraded by the final pathological diagnosis. If sonography is performed by an experienced gynecologic oncologist, this examination is more reliable than tumor markers. However, intraoperative frozen section should still be performed during surgery for patients with ovarian tumors.     

Changes in serum levels of gynecological tumor markers throughout the period from early gestation to puerperium]

The aim of this study is to elucidate the change in serum levels of gynecological tumor markers throughout the period from the early gestational stage to puerperium. We measured eight tumor markers of--CA 125, TPA, SCC, AFP, haptoglobin, ferritin, CA19-9 and CEA--in 17 healthy women with a normal course of pregnancy, delivery and puerperium, and obtained the following results: 1) Profiles of change in serum levels of CA125, SCC, haptoglobin and ferritin were similar during pregnancy, with those levels being the highest at 4-15 weeks of gestation and declining gradually from 16 to 27 weeks. Serum levels of these four markers decreased significantly (p less than 0.01) at 16-27 and 28-40 weeks of gestation, respectively. 2) A significant (p less than 0.01) increase in CA125 and SCC was observed 2 hours after delivery compared with the levels in the first stage of delivery. However, these two markers decreased to the normal range after the fifth day postpartum. 3) Serum TPA decreased significantly (p less than 0.05) in 16-27 weeks of gestation, comparing with those of 4-15 weeks. Serum CA19-9 and CEA remained almost unchanged within the normal range throughout the period from pregnancy to puerperium. 4) Tumor markers of CA125, TPA, SCC, haptoglobin, ferritin and CEA of which serum levels decreased during the course of pregnancy and puerperium might be a clue to judge whether gynecological tumors in pregnant women are malignant or benign.     

超声联合肿瘤标志物预测附件包块良恶性质的临床价值

目的研究术前超声联合肿瘤标志物预测附件包块良恶性质的临床价值。方法回顾性分析2009年1月至2010年10月间,于同济大学附属第一妇婴保健院收治的475例附件包块患者,术前超声评估附件包块性质(包括肿块大小,回声性质和血流信号)和肿瘤标志物(CA125、CA199、AFP、CEA和CA153)检查,与最终手术病理结果比较。结果手术石蜡病理提示卵巢恶性肿瘤100例,交界性肿瘤50例,良性肿瘤325例。术前超声提示囊性肿块183例,其中良性144例(78.7%)、恶性19例(10.4%);超声提示混合性肿块247例,其中良性160例(64.8%)、恶性58例(23.5%);超声提示实性肿块45例,其中良性21例(46.7%)、恶性23例(51.1%)。超声提示混合性或实性肿块与囊性肿块相比,卵巢恶性肿瘤病率显著增加(27.7%vs.10.4%)(P<0.001)。提出卵巢肿瘤预测模型1、2、3,模型1:CA125≥35kU/L+超声混合或实性;模型2:CA125≥100kU/L+超声混合或实性;模型3:CA125≥35kU/L+CA199≥37kU/L+超声混合或实性。结论超声提示附件混合性或实性包块同时合并CA125升高者,卵巢恶性肿瘤发生率显著增高。     

IL-6、CRP、CA_(125)在卵巢肿瘤定性诊断中的价值及临床意义

目的 :探讨测定血清IL 6、CRP、CA12 5水平在卵巢肿瘤定性诊断中的价值及临床意义。方法 :取卵巢肿瘤 61例患者的血浆及 17例合并腹水患者的腹水 ,用ELISA法及胶乳凝集法测定IL 6、CA12 5、CRP。结果 :IL 6诊断卵巢癌敏感性为 80 .9% ,特异性为77.3%。CA12 5诊断卵巢癌敏感性为 85 .7% ,特异性为 80 .9%。这二项指标联合检测 ,敏感性为 92 .5 % ,特异性 73.9%。CRP诊断卵巢癌敏感性达 76.2 % ,特异性 60 .0 %。临床分期晚、组织分化低者血清及腹水IL 6、CA12 5水平明显升高。结论 :IL 6、CA12 5是卵巢肿瘤定性诊断的良好指标 ,联合检测可提高定性诊断的敏感性及特异性。腹水或血中IL 6、CA12 5水平可为卵巢癌早期诊断、分期及判断预后提供有效的参考指标。