Berek J S, Bast R C
Gynecologic Oncology Service, UCLA School of Medicine 90024-1740, USA.
Cancer. 1995 Nov 15;76(10 Suppl):2092-6. doi: 10.1002/1097-0142(19951115)76:10+<2092::aid-cncr2820761331>3.0.co;2-t.
The use of serum tumor markers for the early detection of ovarian cancer has been limited because of their low sensitivity and low positive predictive value. CA 125 levels are elevated in only about one half of women with Stage I ovarian cancer, thus researchers have focused on using the serial measurement of complementary markers to improve the sensitivity, specificity, and positive predictive value of this approach for screening.
Multiple serum markers have been analyzed in women with early stage epithelial ovarian cancer. CA 125, CA 15-3, C19-9, CA 54-61, CA 72-4, CEA, HMFG2, IL-6, IL-10, LSA, M-CSF, NB70K, OVX1, PLAP, TAG72, TNF, TPA, and UGTF have been studied alone and in combination in this setting. Complementarity and logistic regression analyses have been performed to assess those markers with the highest likelihood of improving sensitivity and specificity for early detection. Serial analysis of a second-generation CA 125 measuring the intercept (initial level) and slope (change of levels over time) can be used to discriminate malignant cases from benign and normal cases.
Analyses have shown that the serial measurement of the new, more sensitive CA 125 has a high sensitivity (83%), specificity (99.7%), and positive predictive value (16%) for the early detection of ovarian cancer. OVX1 used in combination with CA 125 provides the best complementarity. Serial measurements of the two markers have sensitivities in the range of that for transvaginal ultrasonography.
The serial measurement of complementary serum markers can improve the use of marker screening for epithelial ovarian cancer. With the use of several different methods of analysis, it has been shown that this approach improves the sensitivity, specificity, and positive predictive value of serum markers CA 125 and OVX1. A procedure that measures complementary serum markers over time can be used as a primary screening technique followed by transvaginal ultrasonography. This could provide a cost-effective means of early detection and could significantly decrease the probability of surgical intervention for false-positive test results.
血清肿瘤标志物用于卵巢癌早期检测的应用一直受限，因其敏感性低且阳性预测值低。仅约一半的Ⅰ期卵巢癌女性患者CA 125水平升高，因此研究人员致力于通过连续检测互补标志物来提高该筛查方法的敏感性、特异性和阳性预测值。
对早期上皮性卵巢癌女性患者的多种血清标志物进行了分析。在此研究中，单独及联合研究了CA 125、CA 15 - 3、C19 - 9、CA 54 - 61、CA 72 - 4、癌胚抗原（CEA）、高分子量粘液糖蛋白2（HMFG2）、白细胞介素 - 6（IL - 6）、白细胞介素 - 10（IL - 10）、乳酸脱氢酶同功酶A（LSA）、巨噬细胞集落刺激因子（M - CSF）、NB70K、OVX1、胎盘碱性磷酸酶（PLAP）、肿瘤相关糖蛋白72（TAG72）、肿瘤坏死因子（TNF）、组织多肽抗原（TPA）和尿苷二磷酸葡萄糖醛酸基转移酶（UGTF）。进行了互补性和逻辑回归分析，以评估那些最有可能提高早期检测敏感性和特异性的标志物。对第二代CA 125进行连续分析，测量截距（初始水平）和斜率（水平随时间的变化），可用于区分恶性病例与良性和正常病例。
分析表明，新型、更敏感的CA 125连续检测对卵巢癌早期检测具有高敏感性（83%）、特异性（99.7%）和阳性预测值（16%）。OVX1与CA 125联合使用具有最佳互补性。两种标志物的连续检测敏感性与经阴道超声检查相当。
互补血清标志物的连续检测可改善上皮性卵巢癌标志物筛查方法的应用。通过使用几种不同的分析方法，已证明该方法提高了血清标志物CA 125和OVX1的敏感性、特异性和阳性预测值。一种随时间测量互补血清标志物的程序可作为主要筛查技术，随后进行经阴道超声检查。这可为早期检测提供一种经济有效的手段，并可显著降低因假阳性检测结果而进行手术干预的可能性。
