CA125 expression at clinical diagnosis by ovarian carcinoma not detected through antecedent serum CA125 screening

At the time of clinical presentation with ovarian carcinoma, 85% of women have an elevated serum level of the CA125 antigen, but the duration of the preclinical phase of expression of CA125 is unknown. From the database of The Royal London Hospital ovarian cancer screening project, 19 women were identified who had a serum CA125 level <30 IU ml⁻¹, measured between 2 and 24 months prior to their clinical diagnosis of ovarian cancer. Histological sections of tumor removed from these women were reviewed. In 17 cases tumor tissue was immunocytochemically stained for CA125 expression. Tumor blocks of 40 women presenting clinically with ovarian cancer with known preoperative CA125 levels were also stained for CA125 expression. The serum CA125 level at the time of diagnosis was available in six of the 19 screening study cases, four of which had levels> 30 IU ml⁻¹. In five of the 13 cases with unknown serum CA125 levels, ovarian tumor tissue expressed CA125. Among the 40 controls, 24 tumors expressed CA125 and all 24 had a serum level greater than 47 IU ml⁻¹. An annual screening test using serum levels of CA125 at a cut-off of 30 IU ml⁻¹, cannot detect all cases of ovarian cancer that express the antigen at the time of clinical diagnosis. The development of a panel of complementary tumor markers will be necessary to provide a test with a higher sensitivity for the detection of preclinical ovarian cancer.     

血清CA125监测卵巢上皮性癌术后复发界值探讨

目的探讨CA125在监测卵巢上皮性癌术后复发的界值。方法回顾性总结分析四川大学华西二院2005年1月至2009年12月收治的卵巢上皮性癌170例手术后患者,未复发组135例,复发组35例,以绝经后体格检查正常的105例妇女及除卵巢恶性肿瘤之外的65例术后无复发的妇科恶性肿瘤患者作为对照组。以CA125值为5kU/L、10kU/L、15kU/L、20kU/L、25kU/L、30kU/L、35kU/L分别作为界值,比较各界值对判断卵巢上皮性癌术后复发的敏感度、特异度。结果卵巢上皮性癌术后无复发患者、绝经后妇女及妇科恶性肿瘤术后患者CA125中位数值分别为7.5kU/L、8.4kU/L、6.9kU/L;均数±标准差分别为(8.3±3.6)kU/L、(9.1±4.2)kU/L、(7.3±2.6)kU/L。以15kU/L为界值判断复发,敏感度、特异度分别为74.3%、97.0%。结论以15kU/L为CA125界值配合影像学检查监测卵巢上皮性癌术后病情变化,敏感度提高,能够早期发现微小癌灶存在,早期治疗,延长患者生存期。     

CA125测定联合B超检查对卵巢上皮癌的诊断和预后的价值分析

目的　探讨CA1 2 5检测联合B超检查在卵巢上皮癌的诊断及预后的价值。方法　卵巢上皮癌、卵巢良性肿瘤术前进行CA1 2 5测定和B超检查 ,卵巢上皮癌者术后 1周及每次化疗前复查CA1 2 5和B超。结果　术前卵巢上皮癌的CA1 2 5明显高于卵巢上皮癌术后组及卵巢良性肿瘤组 ,Ⅲ、Ⅳ期卵巢上皮癌的CA1 2 5明显高于Ⅰ、Ⅱ期 ;2 7%的CA1 2 5>6 0 0U/ml患者能施行理想的肿瘤细胞减灭术。CA1 2 5联合B超使卵巢上皮癌的诊断阳性率提高达 95 %。结论　CA1 2 5是卵巢上皮癌诊断和判断预后的特异性指标 ,CA1 2 5联合B超检查可提高卵巢上皮癌的诊断率。     

CA125 and radioimmunoimaging in monitoring of epithelial ovarian carcinoma

Serum CA125 was measured by monoclonal antibody-OC125 in 50 primary and 29 suspected recurrent ovarian cancer patients. Among the later, RII examination by using 131I labelled polyclonal antibody-OCOV3 was carried out in 16 cases at the same time. For the suspected recurrent cases, the results, as checked by surgico-pathological findings, revealed a corroborative rate of 79.3% for CA125 assay and 87.5% for RII technique. The positive predictive value of both CA125 assay and RII were 100%, while the negative predictive value was only 25% for CA125 assay and 50% for RII technique. However, for each individual case if the results of the two tests were combined, the negative predictive value was also 100%. Preoperative CA125 level had no significant relationship with the prognosis in primary cases. But the two year survival rate for recurrent cases with a preoperative CA125 less than or equal to 35,000 U/L was much higher than those with CA125 greater than 35,000 U/L.     

Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.     

血清CA125半衰期判定卵巢上皮性癌预后的价值

目的 探讨血清ＣＡ１２５半衰期在卵巢上皮性癌中的预后价值。方法 回顾性分析３０例卵巢上皮性癌患者在化疗过程中血清ＣＡ１２５半衰期值（ｔ１／２）与生存时间的关系。结果 血清ＣＡ１２５半衰期值（ｔ１／２）≤２０天组的中位生存时间为３６个月,ｔ１／２〉２０天组中完全缓解率为２７．３％,两者存在极显著差异（ｐ＝０．００１）。多因素生存分析表明：ＣＡ１２５半衰期和细胞分级、残余瘤灶大小均是独立的预后因素。结     

血清CA125值的变化对判断上皮性卵巢癌疗效及预后的临床研究

目的 探讨化疗前后CA125变化对上皮性卵巢癌疗效、预后判定的临床价值.方法 对北京协和医院1989-12-01-2001-12-01初治的203例上皮性卵巢癌患者进行血清CA125的检测,计算化疗2疗程后血清CA125值较化疗前下降的百分比,观察CA125不同组复发中位时间及生存期限的差异.结果 203例患者中有102例复发,CA125下降≥75%组、50%～<75%组、<50%组各组复发的中位时间差异有显著性(F=8.422,P<0.001),且CA125下降<50%组的复发时间短;Kaplan-Meier法计算生存率,得出化疗2疗程后CA125值下降水平≥75%组的中位生存时间为42.8个月,50%~<75%组为34.6个月,<50%组为24.0个月,CA125上升组为9.3个月,以log-rank时序检验比较各组生存率曲线的分布差异有显著性(X2=33.097,P<0.001);COX风险模型分析上皮性卵巢癌预后的多因素结果表明CA125下降水平、FIGO分期、术后残存病灶大小与卵巢上皮癌预后明显相关.结论 化疗2疗程后CA125值与化疗前下降的百分比对上皮性卵巢癌的预后评定有一定的临床价值,检测该指标可协助判断复发,尽早予以相应的治疗措施.     

Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma

OBJECTIVES: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier. METHODS: We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program. RESULTS: CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125. CONCLUSION: The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.     

Elevated CA 125 serum levels and epithelial ovarian cancer metastatic to retroperitoneal lymph nodes

Elevations in CA 125 levels have been reported in approximately 80% of patients with epithelial ovarian cancer. Studies demonstrate that elevations of CA 125 at the time of second-look procedures correlate with the presence of tumor in 100% of cases. Two cases are reported with elevated CA 125 in which clinical examination and noninvasive studies with CAT scans failed to demonstrate tumor. In both cases laparotomy was performed because of the elevation of CA 125. Although intraabdominal exploration did not reveal the source of the CA 125 elevation, extensive retroperitoneal dissection demonstrated microscopic tumor in retrocaval lymph nodes in both cases. The ability to monitor patients with CA 125 is demonstrated and the importance of elevated antigen levels emphasized. Benign conditions associated with falsely positive CA 125 are discussed.     

The prognostic significance of the half-life of serum CA 125 in patients responding to chemotherapy for epithelial ovarian carcinoma

Various prognostic factors were studied in 29 patients with stage III or IV ovarian cancer who responded to initial chemotherapy after initial diagnostic surgery. The half-life of CA 125 in serum during initial chemotherapy was the most important prognostic indicator for survival (P less than 0.001) and the chance of achieving complete remission (P = 0.012). A CA 125 half-life of less than 20 days, 20-40 days and greater than 40 days appears to identify patients with a good, intermediate or poor prognosis, the two year actuarial survival being 76%, 48% and 0% respectively. The change of achieving a complete remission was 15% and 67% respectively for patients with a serum CA 125 half-life of greater than 20 or less than 20 days.     

血清CA125用于预测上皮性卵巢癌、输卵管癌及腹膜癌化疗反应性的研究

目的:探讨上皮性卵巢癌、输卵管癌及腹膜癌对铂类+紫杉醇类化疗敏感性与CA125变化的关系。方法:选取2009年1月至2011年5月上海市第一妇婴保健院手术及化疗的71例上皮性卵巢癌、6例输卵管癌和1例腹膜癌患者,以3次化疗后血清CA125能否降至正常(<35kU/L),术后前3次化疗后每次CA125同上次比较能否降低50%作为判断铂类敏感的指标,比较分析化疗敏感型患者CA125数值变化规律。结果:(1)术前CA125数值对于判断患者第2次及第3次化疗后血清CA125能否下降50%以上具有统计学意义(P<0.01);(2)术后首次CA125数值对于判断患者第2次(P=0.028),第3次(P<0.01)化疗后血清CA125能否下降50%,以及3次化疗后血清CA125能否降至正常(P=0.046)具有统计学意义;(3)较早FIGO分期(FIGOⅠ～Ⅱ期),无腹水,满意的肿瘤灭减术也是决定患者化疗敏感性的临床指标。结论:术前和术后血清CA125水平、较早的FIGO分期、无腹水、满意的肿瘤减灭术是影响卵巢癌、输卵管癌、腹膜癌患者化疗敏感性的有意义的临床指标。     

晚期卵巢上皮性癌患者初次治疗过程中血清CA125水平变化与其预后的关系

目的 探讨晚期(Ⅲ～Ⅳ期)卵巢上皮性癌(卵巢癌)患者初次治疗过程中血清CA125水平变化与其预后的关系.方法 选择1998年1月-2003年12月间中山大学肿瘤防治中心妇瘤科收治的142例晚期卵巢癌患者,回顾性分析其初次治疗过程中血清CA125水平的变化,采用Kaplan-Meier法计算其累积生存率,并采用Cox风险比例回归模型分析血清CA125水平的变化对患者预后的影响.结果 根据患者治疗前血清CA125水平不同分为≤500、>500～1500和>1500 kU/L,其3年累积生存率(分别为64%、71%及64%)比较,差异无统计学意义(P>0.05).术后接受3个疗程化疗后,血清CA125水平降至正常(0～35 kU/L)的77例患者的3年及5年累积生存率分别为84%及56%,明显高于血清CA125水平仍为异常的48例患者(分别为42%、15%,P<0.01).多因素分析表明,残留灶直径(P<0.01)及3个疗程化疗后血清CA125水平(P<0.01)是影响晚期卵巢癌患者预后的独立的因素.进一步分层分析表明,接受了满意的肿瘤细胞减灭术(残留灶直径≤1 cm)的患者中,3个疗程化疗后血清CA125水平降至正常者的3年及5年累积生存率分别为88%、64%,明显高于化疗后血清CA125笛水平仍为异常者(分别为52%、18%,P<0.01);同样,接受了不满意的肿瘤细胞减灭术(残留灶直径>1 cm)的患者中,3个疗程化疗后血清CA125水平降至正常者的3年和5年累积生存率分别为74%、32%,明显高于化疗后血清CA125水平仍为异常者的33%、13%(P<0.01).结论 3个疗程化疗后血清CA125水平正常与否可预测晚期卵巢癌患者的预后,且无论初次手术是否为满意的肿瘤细胞减灭术,3个疗程化疗后血清CA125水平降至正常者较未降至正常者预后好.     

The prognostic implications of low serum CA 125 levels prior to the second-look operation for stage III and IV epithelial ovarian cancer.

Second-look laparotomy is performed to evaluate response to chemotherapy and to determine the need for additional treatment. The relationship between absolute levels of serum CA 125 less than 35 u/ml and disease status at second-look operation was evaluated in 95 patients with advanced-stage epithelial ovarian cancer. Eighty-six patients had Stage III disease and nine patients had Stage IV cancer. Residual tumor was documented at second-look laparotomy in 52 (55%) of the patients studied. Forty-nine percent of the 82 patients with serum CA 125 values less than 20 u/ml had residual disease. In contrast, 12 of 13 (92%) patients with serum CA 125 values of 20-35 u/ml had residual tumor at second-look laparotomy. All patients with serous cystadenocarcinomas and serum CA 125 values of 20-35 u/ml had residual tumor, and two-thirds of these cases had grossly visible disease. The positive predictive value of a serum CA 125 level of 20-35 u/ml was 0.92. These data suggest that second-look laparotomy should be deferred in patients with advanced-stage ovarian cancer until serum CA 125 values are less than 20 u/ml.     

Use of CA 125 to monitor patients with ovarian epithelial carcinomas

The CA 125 radioimmunoassay has been increasingly used to monitor the course of patients with ovarian epithelial carcinomas. The purpose of this report is to describe our experience in the use of this assay and to better define its clinical utility. Fifty-one patients had serum CA 125 follow-up during primary chemotherapy. All 51 patients demonstrated either a normal CA 125 level at the completion of chemotherapy or a substantial fall in CA 125 values with treatment. In 48 of 51 patients, the drop in CA 125 levels was temporally related to the clinical regression or remission of tumor. Forty of these patients underwent second-look laparotomy; 23 patients (58%) had residual disease. A total of 45 patients had serum CA 125 determinations at the time of second-look laparotomy. Eight patients with microscopic disease and 11 of 18 patients with gross residual disease had a "negative" (less than 35 U/ml) CA 125 level. The predictive value of an elevated CA 125 level was 1.00. However, the predictive value of a negative value was only 0.50. Hence, a negative CA 125 level cannot be a substitute for a second-look laparotomy. Only 7 of 18 patients (39%) with gross residual disease at second-look surgery had an elevated CA 125 level. Patients with an elevated CA 125 and gross residual tumor at the second-look laparotomy uniformly demonstrated large, bulky disease. Furthermore, the survival of patients with gross residual disease at second-look laparotomy correlated with the preoperative CA 125 value. Serum CA 125 determinations also show promise in the follow-up of patients with a negative second-look laparotomy. The serum CA 125 level from patients with a "negative" second-look laparotomy can become elevated months before recurrent disease is appreciated.     

Tumor tissue CA125 in ovarian carcinoma patients with normal serum levels

A good correlation between elevated serum CA125 and its immunolocalization in ovarian tumor tissue has been reported. This study was undertaken in order to assess the presence of CA125 in tumor tissue obtained from ovarian carcinoma patients with normal serum levels. Eleven such ovarian carcinoma patients (nine of them serous) were identified. In seven the level was normal prior to the initial operation, and in four, prior to a positive second-look operation. Immunohistochemical staining of paraffin sections for CA125 was positive in seven of the tumor tissue samples. Tumor tissue of most ovarian carcinoma patients with a preoperative normal serum CA125 contains the antigen, but an undetermined mechanism prevents elevated serum levels.     

Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer

Serum CA 125 levels were measured preoperatively in 100 women undergoing diagnostic laparotomy for palpable adnexal masses. All 11 patients with frankly malignant nonmucinous ovarian carcinoma had serum CA 125 levels greater than 35 U/mL and nine of the 11 had serum CA 125 levels greater than 65 U/mL. If patients with mucinous and borderline lesions were included, serum CA 125 was greater than 35 U/mL in 11 of 18 and greater than 65 U/mL in nine of 18 patients. Among 14 individuals with pelvic masses and CA 125 greater than 65 U/mL, 13 had some form of gynecologic malignancy. These results suggest that CA 125 assay can be used as a diagnostic adjunct for discriminating benign from malignant pelvic masses.