Romagnolo Cesare, Leon Antonette E, Fabricio Aline S C, Taborelli Martina, Polesel Jerry, Del Pup Lino, Steffan Agostino, Cervo Silvia, Ravaggi Antonella, Zanotti Laura, Bandiera Elisabetta, Odicino Franco E, Scattolo Novella, Squarcina Elisa, Papadakis Christine, Maggino Tiziano, Gion Massimo
Unit of Gynecology and Obstetrics, G. Fracastoro Hospital, Via Circonvallazione 1, 37047 San Bonifacio, Verona (VR), Italy.
Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy.
Gynecol Oncol. 2016 May;141(2):303-311. doi: 10.1016/j.ygyno.2016.01.016. Epub 2016 Jan 19.
This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC).
A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC).
Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%).
Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
本多中心研究旨在评估人附睾蛋白4（HE4）、癌抗原125（CA125）及卵巢恶性肿瘤风险算法（ROMA）在鉴别诊断上皮性卵巢癌（EOC）中的性能。
连续纳入405例因盆腔肿物可疑需手术以明确是否为EOC而转诊至妇科肿瘤专家处的患者；387例患者符合纳入标准：290例为良性疾病；15例为交界性肿瘤；82例为肿瘤（73例为EOC）。
计算最佳临界值时，CA125、HE4和ROMA在鉴别EOC患者与良性疾病患者方面具有良好的诊断性能：绝经前，特异性（SP）>86.6，敏感性（SN）>82.6，曲线下面积（AUC）≥0.894；绝经后，SP>93.2，SN>82，AUC≥0.928。将SP固定为98%时，良性疾病患者与EOC患者的性能指标如下：绝经前，CA125的SN为65.2%，阳性预测值（+PV）为75%，阳性似然比（+LR）为26.4；HE4的SN为69.6%，+PV为76.2%，+LR为28.1；ROMA的SN为69.6%，+PV为80%，+LR为35.1；绝经后，CA125的SN为88%，+PV为95.7%，+LR为38.7；HE4的SN为78%，+PV为95.1%，+LR为34.3；ROMA的SN为88%，+PV为97.8%，+LR为77.4。使用常规临界值时ROMA显示出更好的SP和SN平衡值（绝经前，SN为87%，SP为86.1%；绝经后，SN为90%，SP为94.3%）
总体而言，ROMA在鉴别EOC与良性疾病方面显示出良好的平衡诊断性能。HE4和CA125在+PV和+LR方面的显著差异表明这两种标志物在EOC诊断中可能至少部分发挥不同作用，HE4在疾病组中诊断EOC患者时似乎比CA125更有效，在绝经前和绝经后阶段的早期肿瘤中也是如此。
