Preoperative differentiation of benign and malignant non-epithelial ovarian tumors: clinical features and tumor markers / Diferenciação pré-operatória de tumores ovarianos não epiteliais benignos e malignos: características clínicas e marcadores tumorais

Abstract Objective To evaluate the role of clinical features and preoperativemeasurement of cancer antigen 125 (CA125), human epididymis protein(HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. Methods One hundred and nineteen consecutive women with germ cell, sex cordstromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. Results Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, amongmalignant, fourwere immatureteratomas. Themost common tumors in the sex cordstromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign andmalignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. Conclusion Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant caseswere diagnosed at initial stages with good prognosis. Themeasurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

Resumo Objetivo Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. Métodos Cento e dezenovemulheres consecutivas comtumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. Resultados Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estromamalignos foram tratadas comcirurgia preservadora de fertilidade. Cinco (71,4%)mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. Conclusão Os tumores de ovário não epiteliais foram benignos namaioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico préoperatório desses tumores.

Comparison of serum cancer antigen 125, human epididymis protein 4, ROMA, and CPH-I for diagnosis of ovarian cancer in Chinese patients with ovarian mass / 南方医科大学学报

OBJECTIVE@#To compare the performance of serum cancer antigen 125 (CA125), human epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA) and Copenhagen index (CPH-I) for differential diagnosis of benign and malignant diseases in patients with ovarian mass.@*METHODS@#We retrospectively analyzed the data of 719 women with pelvic mass, and the performance of preoperative serum levels of CA125 and HE4, ROMA and CPH-I for differential diagnosis of the masses was compared.@*RESULTS@#Of the 710 women analyzed, 531 were diagnosed with benign ovarian lesions, 44 with borderline ovarian tumors (BOTs), 119 with epithelial ovarian cancers (EOCs), and 25 with non-EOCs. In differentiating ovarian cancer (OC) and BOT from benign lesions, the area under the receiver-operator characteristic (ROC) curve (AUC) was 0.854 for HE4, 0.856 for ROMA, 0.854 for CPH-I, and 0.792 for CA125, demonstrating better diagnostic performance of HE4, ROMA, and CPH-I than CA125 alone; the diagnostic sensitivity was 56.9% for HE4, 70.2% for CA125, 69.1% for ROMA, and 63.8% for CPH-I; the specificity was the best with HE4 (94.4%) and CPH-I (94.7%). In sub-analysis of EOC benign lesions, the AUCs of HE4, ROMA, and CPH-I increased to 0.946, 0.947, and 0.943, respectively, all greater than that of CA125 (0.888). In other sub-analyses, HE4, ROMA, and CPH-I all showed greater AUCs than CA125 alone.@*CONCLUSIONS@#This study confirms the accuracy of HE4, ROMA, and CPH-I for differentiating malignant from benign ovarian mass, and all these 3 tests show better performance than CA125. Furthermore, HE4 and CPH-I is superior to ROMA and CA125 in terms of specificity, while CA125 and ROMA have better diagnostic sensitivities.

Effect of WFDC 2 silencing on the proliferation, motility and invasion of human serous ovarian cancer cells in vitro

OBJECTIVE@#To investigate effect and possible mechanisms of silencing human WFDC2 (HE4) gene on biological behavior changes as cell proliferation, apoptosis, movement and invasion of human serous ovarian cancer cell line SKOV3.@*METHODS@#Lentiviral WFDC2 gene sequence of small interfering siRNA was stablely transfected into SKOV3 identified by Q-PCR and western-blot. Obtained SKOV3 stable strains with silenced HE4 were measured by proliferation, apoptosis, migration, and invasion.@*RESULTS@#Gene sequencing showed that the oligonucleotides were successfully inserted into the expected site. After silencing HE4 in the SKOV3, proliferation was significantly inhibited (P<0.05). G(0)/G(1) phase was arrested by the cell cycle (P<0.01) and capacity of the migration and invasion decreased significantly (P<0.01). Slight early apoptosis ratio and no change of late apoptosis were found without change of Caspase-3 or Bcl-2 protein. Proteins involved in ERK pathway as phosphorylated protein as p-EGFR, p-ERK decreased and protease protein involved in tissue remodeling as matrix metalloproteinases MMP-9, MMP-2 and cathepsin B decreased compared with control group.@*CONCLUSIONS@#HE4 gene plays an important role in regulating proliferation, apoptosis, migration, invasion of serous ovarian cancer cells by ERK pathway and protease system. Its role in apoptosis needs to be further explored, and it may be a potential target for serous ovarian cancer.

Expression of serum human epididymal secretory protein E4 at low grade and high grade serous carcinomas

OBJECTIVE@#To investigate the value of serum human epididymis protein 4 (HE4) in differential diagnosis of patients with low-grade serous (LGSC) and high-grade serous carcinoma (HGSC) serous ovarian cancer.@*METHODS@#LGSC and HGSC serous ovarian cancer were diagnosed by the two-tier grade system, serum levels of HE4 and carbohydrate antigen 125 (CA125) were measured by ELISA and radioisotope method, respectively in 60 serous ovarian cancer patients. HE4 and TP53 protein in cancer tissue were measured by immunohistochemical method.@*RESULTS@#The difference in density of HE4 and TP53 protein was significant between LGSC and HGSC tissue, while serum CA125 did not show significant difference between different serum samples. There was significant difference in serum HE4 levels between LGSC and HGSC, and the result was different within FIGO (I+II) stage, suggesting HE4 was not a reliable biomarker for the discrimination between LGSC and HGSC. HE4 had potential as a biomarker for the discrimination between LGSC and HGSC but the role in early diagnosis was limited.@*CONCLUSIONS@#HE4 may be a reliable marker for differential diagnosis of LGSC and HGSC. But its role in early diagnosis of LGSC and HGSC need to be confirmed from the perspective of two-tier grade system.