Woolas R P, Xu F J, Jacobs I J, Yu Y H, Daly L, Berchuck A, Soper J T, Clarke-Pearson D L, Oram D H, Bast R C
Royal London Hospital, Cambridge University, England.
J Natl Cancer Inst. 1993 Nov 3;85(21):1748-51. doi: 10.1093/jnci/85.21.1748.
The high overall mortality from ovarian cancer (> 60%) relates, in part, to delays in diagnosis. When ovarian cancer is detected in stage I (International Federation of Gynecology and Obstetrics staging), up to 90% of patients can be cured. Transvaginal sonography can detect early-stage disease with great sensitivity, but it is expensive and lacks specificity. Although serum marker assays could provide a less expensive and more convenient initial screening test, the sensitivity of assays varies. Measurement of serum CA 125 in conjunction with ultrasound screening as a second-line test confers high specificity but detects only about one half of early stage ovarian carcinomas.
The purpose of this retrospective study was to determine whether assays of multiple serum markers would improve sensitivity by detecting a higher percentage of stage I ovarian cancers than the CA 125 assay alone.
Using immunoradiometric assays, we measured preoperative serum levels of CA 125 tumor-associated antigen, macrophage colony-stimulating factor (M-CSF), and OVX1 in 46 patients with stage I ovarian cancer of different histologies and 237 patients with benign pelvic masses. We also assayed sera from 204 apparently healthy women who had participated in a screening trial and remained free from cancer at 1 year of followup. All specimens were obtained from cryopreserved aliquots. Marker levels were considered to be elevated when levels of CA 125 were greater than 30 U/mL, M-CSF levels were greater than 3.1 ng/mL, or OVX1 levels were greater than 12.1 U/mL.
At least one of the serum markers was elevated in 98% of patients with stage I ovarian cancer; CA 125 levels were elevated in 67%. By the same criteria, 11% of healthy individuals and 51% of patients with benign pelvic masses had at least one elevated marker value. Thus, the sensitivity of the combination of assays for the three serum markers was significantly greater than the sensitivity of the CA 125 assay (P < .0005) and specificity was moderate.
A panel of these three tumor markers can identify early-stage ovarian cancer with extremely high sensitivity and moderate specificity.
Elevation of one or more serum markers should be evaluated further as an indication for transvaginal sonography in apparently healthy women. Such a strategy might substantially reduce the expense and improve the specificity of screening compared to the use of ultrasound alone. Prospective studies with a large cohort of patients at high risk for ovarian cancer will be required to confirm these findings.
卵巢癌总体死亡率较高（>60%），部分原因是诊断延迟。当卵巢癌在Ⅰ期（国际妇产科联盟分期）被检测到时，高达90%的患者可以治愈。经阴道超声检查能够以高灵敏度检测早期疾病，但费用高昂且缺乏特异性。尽管血清标志物检测可以提供一种成本较低且更便捷的初始筛查试验，但各检测的灵敏度有所不同。将血清CA 125检测与超声筛查联合作为二线检测具有高特异性，但仅能检测出约一半的早期卵巢癌。
这项回顾性研究的目的是确定多种血清标志物检测是否能通过检测出比单独CA 125检测更高比例的Ⅰ期卵巢癌来提高灵敏度。
我们使用免疫放射分析方法，测量了46例不同组织学类型的Ⅰ期卵巢癌患者、237例盆腔良性肿块患者术前血清中CA 125肿瘤相关抗原、巨噬细胞集落刺激因子（M-CSF）和OVX1的水平。我们还检测了204名参与筛查试验且在1年随访时无癌症的明显健康女性的血清。所有标本均取自冷冻保存的等分试样。当CA 125水平大于30 U/mL、M-CSF水平大于3.1 ng/mL或OVX1水平大于12.1 U/mL时，标志物水平被视为升高。
98%的Ⅰ期卵巢癌患者至少有一项血清标志物升高；67%的患者CA 125水平升高。按照相同标准，11%的健康个体和51%的盆腔良性肿块患者至少有一项标志物值升高。因此，三种血清标志物联合检测的灵敏度显著高于CA 125检测（P <.0005），且特异性中等。
这三种肿瘤标志物组合能够以极高的灵敏度和中等的特异性识别早期卵巢癌。
对于明显健康的女性，应进一步评估一种或多种血清标志物升高作为经阴道超声检查指征的情况。与单独使用超声相比，这样的策略可能会大幅降低费用并提高筛查的特异性。需要对大量卵巢癌高危患者进行前瞻性研究来证实这些发现。
