Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass

Objective

Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes.

Methods

Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.

Results

809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI = 200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).

Conclusion

HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.     

IOTA SR 与 CA125、HE4、ROMA、RMI1、GI-RADS对卵巢良恶性肿瘤的诊断价值比较

目的 探讨糖链多肽抗原125(CA125)、人附睾蛋白4(HE4)、恶性肿瘤风险算法(ROMA)、恶性风险指数1(RMI1)、国际卵巢肿瘤分析简单规则(IOTA SR)、妇科影像报告与数据系统(GI-RADS)在卵巢良恶性肿瘤鉴别诊断中的价值.方法 选取2019年7 月至2020年7 月于锦州医科大学附属第一医院83例...     

血清miR-222、HE4及CA125水平联合ROMA指数对上皮性卵巢癌的诊断价值

目的:探讨血清miR-222、血清人附睾蛋白4(HE4)及糖类抗原125(CA125)水平联合ROMA指数对上皮性卵巢癌(EOC)的诊断价值.方法:选取2016年1月至2019年12月海南西部中心医院收治的120例EOC患者、100例上皮性卵巢良性肿瘤患者和50例正常健康女性作为研究对象.实时定量PCR法检测miR-2...     

血清HE4和CA125联合检测预测盆腔包块患者卵巢癌的风险

目的:探讨新型肿瘤标记物人附睾分泌蛋白4(HE4)和CA125联合检测预测盆腔包块患者上皮性卵巢癌(EOC)风险的价值。方法:将诊断为盆腔包块拟行手术的患者纳入本研究。测定患者术前血清HE4和CA125水平,分别用绝经后和绝经前预测模型(ROMA)将患者划分至高危组和低危组,评估预测模型的应用价值。结果:评估了191例患者,其中138例盆腔良性疾病,53例盆腔恶性肿瘤,包括36例EOC。绝经后组盆腔良性疾病12例,8例划分至低危组,特异性66.7%(95%CI=40.0～93.3),恶性肿瘤37例,35例划分至高危组,敏感性94.6%(95%CI=87.0～101.9),EOC28例(含9例早期),全划分至高危组,敏感性100.0%。绝经前组良性疾病126例,103例划分至低危组,特异性81.7%(95%CI=75.0～88.5),16例恶性肿瘤,12例划分至高危组,敏感性75.0%(95%CI=54.0～96.2),EOC8例(含2例早期),全划分至高危组,敏感性100.0%。结论:ROMA成功地将盆腔恶性肿瘤患者划分至高危组,其中EOC患者全被正确地划分至高危组,可用于将恶性肿瘤患者尤其是EOC患者分流至有治疗经验的肿瘤医师及治疗中心。     

CA125/HE4和超声影像指标在不同类型盆腔包块的分布特征及恶性风险中的评估价值

目的:观察CA125、HE4及超声恶性风险指标在不同类型盆腔包块的分布特征及恶性预测价值,探讨更优化的卵巢癌风险评估方法。方法:选取2015年1月到2016年6月第三军医大学附属西南医院妇科收治的盆腔包块手术患者305例,依据术后病理结果将患者分为良性组(223例)、交界性肿瘤组(12例)、卵巢癌组(70例)。分析CA125/HE4和超声指标的分布特征并评估其恶性风险预测的灵敏度、特异度。结果:上皮性卵巢癌组中CA125和HE4值显著升高,与非上皮性卵巢癌和良性组比较,差异均有统计学意义(P0.001);非上皮性卵巢癌与良性组比较,差异无统计学意义(P0.05)。卵巢癌组与交界性肿瘤组的CA125值比较,差异无统计学意义(P=0.31),交界性肿瘤的HE4值低于上皮性卵巢癌,差异有统计学意义(P0.05)。良性组子宫内膜异位囊肿CA125升高,HE4无升高,与上皮性卵巢癌比较,差异均有统计学意义(P0.001)。超声指标中,肿块血流、肿块内乳头结构、肿块有实性部分、腹水、肿块直径100mm及多个分隔囊腔六项指标的阴性预测值达78.0%~86.9%。肿块血流、乳头结构、腹水对卵巢癌诊断的特异性均达90%以上。结合血清学和超声指标,建立绝经前卵巢癌风险回归预测模型。结论:CA125和HE4升高分布于上皮性卵巢癌和交界性肿瘤,是其敏感的评估指标。单项CA125升高多分布于卵巢子宫内膜异位囊肿,HE4值是鉴别指标之一。超声六项指标灵敏度低但特异度高,其阴性预测值利于识别恶性风险。本研究的绝经前卵巢癌风险模型有助于卵巢癌的判别,且方法简便。     

The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass

ObjectiveThe purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malignant pelvis masses in Asian women.MethodsThis was a prospective, multicenter (n = 6) study with patients from six Asian countries. Patients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).ResultsA total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensitivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk.ConclusionROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.     

The value of preoperative serum CA 125 levels in patients with a pelvic mass

Serum CA 125 measurements were obtained before operation in 250 consecutive patients admitted with the diagnosis of a pelvic mass. We examined and operated on all patients. Elevated preoperative serum CA 125 levels were more predictive of malignancy in postmenopausal than in premenopausal women (0.86 vs 0.67), but normal levels did not preclude malignancy in either group. Possible limitations of routine measurement of serum CA 125 in the work-up of patients with a pelvic mass are discussed.     

The differential diagnostic potential of a panel of tumor markers (CA 125, CA 15-3, and CA 72-4 antigens) in patients with a pelvic mass

OBJECTIVE: The purpose of this study was to assess the differential diagnostic potential of a combination of CA 125, CA 15-3, and CA 72-4 antigens in the definition of malignant disease, especially ovarian carcinoma in patients with a pelvic mass. STUDY DESIGN: A total of 412 patients were evaluated in a multicenter, retrospective study. RESULTS: Two hundred twenty-six malignant, 171 benign pelvic tumors (of which 129 were benign ovarian tumors), and 15 borderline tumors were evaluated. One hundred thirty-three patients had ovarian carcinoma. In 76 cases (55%), the International Federation of Gynecology and Obstetrics stage was III or IV. Borderline tumors (n = 15) were excluded from the statistical calculations. CA 125 antigen was the most sensitive marker for ovarian carcinoma (81%). The highest specificity and positive predictive value was obtained with CA 15-3 antigen (95% and 92%, respectively). Considering a concomitant elevation of all 3 markers as positive, a positive predictive value of 97% was found. However, only 28% of the patients in the total group and 41% of the patients with ovarian carcinoma had a concomitant elevation of all 3 markers. The combination of all 3 markers with levels below the cut-off resulted in a (false-positive) positive predictive value for malignancy between 12% and 36%. With the use of logistic regression analysis, we found a correct prediction in 73% of the cases. CA 15-3 antigen makes the most significant (P <.0001) contribution to the logistic model in the prediction of malignancy in the total group, with all pelvic masses with an odds ratio of 3.86. CONCLUSION: The combination of a simultaneous elevated level of CA 125, CA 15-3, and CA 72-4 antigens was predictive for malignant disease in almost all cases. However, such concomitant elevation was found in few of the malignant masses. Logistic regression analysis revealed that CA 15-3 antigen makes the most significant contribution to a model for the prediction of malignancy in the total group. The logistic model gave a correct prediction in 73% to 83%. The present tumor marker panel seems inferior to combinations with other test modalities, which include ultrasonography and/or physical examination and/or menopausal status or age.     

Mesovarian hemangioma presenting as massive ascites, pelvic mass, and elevated CA125

Abstract.   Abu J, Brown L, Ireland D, Sizeland E. Mesovarian hemangioma presenting as massive ascites, pelvic mass, and elevated CA125. Int J Gynecol Cancer 2006; 16(Suppl. 1): 412–414.
We present the case of a 48-year-old woman with pelvic mass, ascites, and an elevated CA125 mimicking advanced-stage ovarian cancer. She underwent laparotomy, drainage of ascites, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and infracolic omentectomy. Histology confirmed this to be mesovarian hemangioma, a benign condition.     

No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting

Objective

About 70% of epithelial ovarian cancer patients (EOC) are diagnosed at advanced stage with a five-year survival rate of only 30%. Whilst CA125 detects peritoneally-spread disease, it has limited sensitivity for early cancers, many of which are potentially curable.

Methods

We compared the new commercially available tumor marker HE4 with CA125 individually, in combination, within the risk of malignancy index (RMI) and the newly defined risk of malignancy algorithm (ROMA). Our prospectively-collected cohort of 160 patients consisted of healthy controls, benign diseases, and borderline tumors/adenocarcinomas of ovarian, tubal, peritoneal and endometrial origin. HE4 and CA125 were measured in serum using standardized ELISA.

Results

Both markers showed similar diagnostic performance in the detection of EOC at clinically defined thresholds (CA125 35 U/ml; HE4 70 pM) but HE4 was not elevated in endometriosis. Comparison of non-malignant diagnoses (n = 71) versus early stage ovarian and tubal cancers (n = 19) revealed that HE4 and ROMA displayed the best diagnostic performance (AUC 0.86/0.87, specificity 85.9%/87.3% and sensitivity 78.9%/78.9%, respectively). Whilst RMICA125 detects peritoneal cancer better than all other models (AUC 0.99, specificity 97.2%, sensitivity 80.0%), there is no other detection benefit from RMI compared to HE4 alone or included in ROMA.

Conclusions

The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers. HE4 is superior to CA125 with or without RMI and ROMA indices. However, we see no benefit from combining both markers in clinical practice.     

盆腔良性肿物伴血清CA125水平升高的临床意义

目的探讨血清CA125水平在妇科良性肿瘤、结核性肿物及其他炎症性肿物、子宫内膜异位症等盆腔良性肿物中的升高情况及临床意义.方法回顾性分析中国医学科学院中国协和医科大学肿瘤医院于1999年1月-2003年12月间收治并经病理检查证实的492例妇科盆腔良性肿物患者的临床资料,其中卵巢良性肿瘤237例,其他盆腔良性肿物如子宫肌瘤、子宫腺肌病、卵巢子宫内膜异位症、盆腔结核及其他炎症性肿物等共255例,所有患者术前均有血清CA125的检测.另随机选取60例卵巢上皮性癌患者作为对照.结果盆腔结核、子宫腺肌病、卵巢子宫内膜异位症及卵泡膜-纤维组肿瘤患者的血清CA125水平中位数值均高于正常值(35 kU/L以下),分别是465.0、88.9、59.0、44.5 kU/L.本组盆腔良性肿物中, 血清CA125水平单例最高值为卵泡膜-纤维组肿瘤(1281.0 kU/L),中位数值最高者为盆腔结核(465.0 kU/L).60例卵巢上皮性癌患者血清CA125水平升高者达95.0%,其中位数值是755.5 kU/L,与良性肿物相比,差异有统计学意义(P<0.01 ).在子宫肌瘤与子宫腺肌病的鉴别诊断中,以血清CA125≥50 kU/L为标准,诊断子宫腺肌病的敏感性、特异性、阳性预测值及阴性预测值相对较高,分别是72%、94%、79%和91%.结论血清CA125水平升高也可见于一些盆腔良性肿物,主要有盆腔结核、子宫腺肌病、卵巢子宫内膜异位症及卵泡膜-纤维组肿瘤等,但其中位数值均明显低于卵巢上皮性癌.血清CA125水平检测有利于子宫肌瘤和子宫腺肌病的鉴别诊断.     

The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125

Archives of Gynecology and Obstetrics - To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients...     

A patient presenting with a pelvic mass, elevated CA-125, and fever

BACKGROUND: Tuberculous peritonitis is a rare event which can mimic advanced stage ovarian cancer. A pelvic mass and an elevated CA-125 is suggestive of an ovarian malignancy; however, benign conditions may be discovered, especially in the premenopausal patient. CASE: A patient with a pelvic mass, ascites, and an elevated CA-125 underwent an exploratory laparotomy for presumed ovarian cancer. Final pathology revealed pelvic tuberculosis without any pulmonary involvement. Acid-fast bacilli were confirmed with polymerase chain reaction in the surgical specimen. DISCUSSION: Pelvic tuberculosis is an uncommon gynecologic condition that presents with ascites, a pelvic mass, and fever. An elevated CA-125 is not specific for ovarian malignancy.     

血清HE4及CA125对子宫内膜癌宫外转移的预测价值

目的:评估术前血清HE4和CA125联合检测在子宫内膜癌(EC)的子宫外转移的诊断价值。方法:回顾分析327例EC患者的临床病理资料,检测血清HE4和CA125水平,分析HE4及CA125与临床病理参数的关系,计算诊断评价指标,绘制受试者工作特征(ROC)曲线,计算AUC值。结果:患者血清HE4和CA125水平与病灶范围大小、肌层浸润深度、肿瘤分化程度、临床分期、有无子宫外转移等有关,差异有统计学意义(P0.01)。血清HE4、CA125单项检测子宫外转移时,HE4敏感度最高,为57.81%,联合诊断能显著提高敏感度达79.68%。两项单独检测的ROC-AUC值分别为0.740、0.714,而联合诊断的ROC-AUC值为0.810,差异有统计学意义(P0.001)。结论:血清HE4和CA125联合预测EC患者的子宫外转移比单项检测更具优势。     

Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125 mimicking advanced ovarian carcinoma: A series of 10 cases

Abstract. Bilgin T, Karabay A, Dolar E, Develioğlu OH. Peritoneal tuberculosis with pelvic abdominal mass, ascites, and elevated CA 125 mimicking advanced ovarian carcinoma.
Ten patients with peritoneal tuberculosis who were operated on for suspected advanced ovarian cancer during a 5-year period were analyzed. These 10 cases constituted 1.4% of the 728 new gynecologic cancer cases diagnosed and treated at our department during the same time period. Data were obtained from patients' files and pathology reports. The mean age of cases was 40.6 ± 6.1 (median 37; range 18–72). Ascites was present together with ill-defined nodularities or thickening in the Douglas pouch and/or in the adnexal areas on pelvic examination in all patients but three, who presented with well-demarcated adnexal masses of about 5 cm in diameter. All patients had elevated serum CA 125 levels with a median of 331 U/ml, (40–560 U/ml). Ultrasound and abdominopelvic CT examinations revealed omental and mesenteric thickening in addition to ascites in all patients, cystic ovarian masses or ovarian enlargement in five, and peritoneal implants in two. Abdominal paracentesis performed in the six cases in whom the findings were felt to be most inconclusive for the diagnosis of ovarian cancer revealed clear exudative fluid with benign cells. Mycobacteria could not be demonstrated on direct preparations. Tuberculosis was diagnosed at laparotomy in all. Patients received antituberculous therapy and serum CA 125 levels returned to normal within 2 months after the beginning of treatment. This case series demonstrates a high rate of misdiagnosis between advanced ovarian cancer and peritoneal tuberculosis. Whereas abdominal paracentesis is useless in ruling out peritoneal tuberculosis, and serum CA 125 levels are not helpful in the differential diagnosis, the latter marker may be useful in the follow-up of patients.     

Management, therapy and outcome of treatment in women with pelvic endometriosis

Sixty-four cases of endometriosis treated between 1980 and 1985 were reclassified according to the R-A.F.S. Twenty-eight of the patients (43.7%) were followed for 24-39 months: in this group we evaluated the efficiency of medical treatment (Danazol), combined medical and conservative surgical or definitive surgical treatment on the basis of the persistence, complete or partial regression of the symptoms. In this group of patients the symptoms regressed completely in 39.28% of the cases; in 28.57% there was a partial regression and persistence or recurrence of the symptoms were reported in 32.14%. These results suggest that the classification system is a key to interpreting treatment.