ABSTRACT: Ovarian cancer remains a leading cause of death from gynecological malignancy. Early diagnosis is the most important determinant of survival. For more than 25 years, cancer antigen 125 (CA 125) has been the criterion standard biomarker for the diagnosis and management of women with epithelial ovarian cancer. This study evaluated human epididymis protein 4 (HE4), a novel ovarian cancer biomarker, both alone and in combination with CA 125 as a diagnostic marker for ovarian cancer in a Chinese population.
Sera from 491 Chinese women with ovarian cancer or nonmalignant disorders and healthy women were analyzed. Sensitivities and specificities for both biomarkers and the combination were determined using predefined cutoffs (HE4>150 pmol/L and CA 125>35 U/mL) and receiver operator characteristic curves to define cutoffs based on 95% and 98% sensitivities.
At baseline, serum HE4 and CA 125 levels were significantly higher in the ovarian cancer group versus the 5 reference groups. Using predefined cutoffs, HE4 specificity for ovarian cancer ranged from 90% to 100%; CA 125 specificity ranged from 36% (benign gynecologic disease) to 99%. Combining both markers yielded specificity for ovarian cancer of 100%. Using receiver operator characteristic curve analysis, the cutoff for 95% and 98% specificity was 102.6 and 150.2 pmol/L for HE4, respectively, and 127.2 and 325.5 U/mL for CA 125, respectively; the sensitivity of CA 125 for distinguishing ovarian cancer from benign gynecologic disease was 54% (95% specificity) and 28% (98% specificity), improving to 78% and 68%, respectively, with the addition of HE4.
Human epididymis protein 4 used in conjunction with CA 125 yields improved specificity for ovarian cancer compared with the use of CA 125 alone, generally similar to results seen in non-Chinese populations.
International Journal of Gynecological Cancer 07/2011; 21(5):852-8. · 1.65 Impact Factor
ABSTRACT: To study the clinical pathological characteristics and high risk factors for borderline ovarian tumor (BOT) and stage I epithelial ovarian cancer (EOC).
A total of 91 patients with BOT and 52 patients with stage IEOC who were diagnosed and treated in the Department of Gynecology, Peking University People's Hospital from November 2002 to May 2010 were recruited in this study. The patients' clinical characteristics were reviewed respectively and compared between the two groups.
The women in BOT group were significantly younger than those in EOC group (41.16 ± 14.95 vs. 50.90 ± 14.37,P<0.01). Compared with women with BOT, women with EOC were more likely to be post-menopausal(42.3% vs. 23.1%,P=0.016) and more with family history of malignant tumors (26.9% vs. 13.2%,P=0.04).There were no significant differences in the size of tumors and the serum level of tumor markers. But the size of solid portion of the tumor of EOC was significantly larger than that of BOT(P<0.01). The extent of the increase of CP2 among the patients with EOC was higher than that among the patients with BOT(256.99 vs. 116.59, P=0.028). There was a statistically significant difference between the two groups in tumors' histopathological type(P<0.01). The serous and mucous tumors were more common in EOC group (90.1%, 82/91). In contrary, endometrioid, clear cells and mixed epithelial cancers were more common in EOC group than serous and mucous cancers (44.2%, 23/52).
Although the clinical presentation of patients with stage I EOC was similar to that of those with BOT, there were significant differences in the patients' age, post-menopausal or not, family history of malignant tumors, size of solid portion of tumors, extent of the increase of the tumor biomarker, especially of CP2 and tumors histopathological type. These clinicopathological characteristics might be helpful for us to make different diagnosis.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 02/2011; 43(1):123-8.
ABSTRACT: To evaluate the value of human epididymis secretory protein 4 (HE4) and CA(125) in the diagnosis of ovarian malignancy.
HE4 and CA(125) in the serum specimens of malignant ovarian tumor group (30 cases), benign ovarian diseases (110 cases; 45 benign ovarian tumor, 57 endometriotic diseases and 8 pelvic inflammation were included) and healthy women group (137 cases) were assayed double blindly. The levels and the diagnosis efficiency of the HE4 and CA(125) were analyzed.
(1) The median levels of HE4 and CA(125) were significantly higher in malignant ovarian tumor group (244 pmol/L and 601 kU/L respectively) than those of the benign ovarian diseases group (32 pmol/L and 22 kU/L respectively) and healthy women group (32 pmol/L and 11 kU/L respectively) (P = 0.000 - 0.029). The median levels of CA(125) were also higher in endometriotic diseases and pelvic inflammation groups (53 and 41 kU/L respectively) than those of benign ovarian tumor group and healthy women group (12 and 11 kU/L respectively; P = 0.000 - 0.031). (2) The positive rate of HE4 was lower than that of CA(125) in malignant ovarian tumor group (P = 0.036). HE4 was negative in benign diseases and healthy women groups. But the positive rates of CA(125) were 56.1% and 5/8 respectively in endometriotic diseases and pelvic inflammation groups and there were significant differences compared with HE4 (P = 0.000). (3) The HE4 assay had advantage over the CA(125) assay in receiver operating characteristic-area under the curve (ROC-AUC) and sensitivity with a specificity of 100% when ovarian malignancy was compared with controls having benign diseases and healthy women, benign tumor or benign diseases groups respectively. The CA(125) assay had advantage over the HE4 assay in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having healthy women group. (4) Combined assay of HE4 and CA(125) was better than CA(125) alone when ovarian malignancy was compared with controls having any group. (5) Combined assay was better than HE4 alone in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having benign diseases and healthy women or healthy women groups. And combined assay was lower in the ROC-AUC and the sensitivity with specificity of 100% than HE4 when ovarian cancers were compared with controls having benign tumors or benign diseases groups respectively. (6) The diagnosis efficiency of the HE4 assay at the level 86 pmol/L determined in ROC curve with controls having benign diseases and healthy women group and at the 95% reference level 50 pmol/L of healthy women or 150 pmol/L recommended by the kit respectively was compared. The sensitivity of 50 pmol/L was 73% higher than 150 pmol/L and 86 pmol/L, while the specificity and positive predictive value were lower (P = 0.002, P = 0.000). The specificity, accuracy and positive predictive value of HE4 assay at the set point of 150 pmol/L and 86 pmol/L were 100%, 96% and 96%. The set point of 86 pmol/L had advantage over 150 pmol/L at the sensitivity of diagnosis, 70% and 63% respectively. But the positive predictive value was 95% lower than 150 pmol/L, being 100%. There was no significant difference (P = 0.883, P = 0.883).
The specificity of HE4 assay is higher than CA(125) assay in the diagnosis of ovarian cancer and HE4 combined with CA(125) assay can improve the diagnoses. The set point of 150 pmol/L is advantageous for the accurate diagnosis, while the set point of 86 pmol/L is advantageous for the screening of malignant ovarian cancer.
Zhonghua fu chan ke za zhi 01/2009; 43(12):931-6.
ABSTRACT: To investigate the clinical feature, risk factors and prognosis of bone metastasis from uterine carcinomas.
Eight cases of bone metastasis of uterine carcinomas in our hospital from Mar 2001 to June 2005 were studied retrospectively. These eight women, aged 35 to 74, suffered from cervical cancer (5/8) and endometrial carcinoma (3/8) respectively.
(1) The interval between diagnosis of primary carcinoma and detection of bone metastases was within 2 years. The average interval was 5.3 months in patients with poorly differentiated tumor, and 21 months in the other patients. (2) Specific pathology type and poorly differentiated carcinomas may be risk factors of bone metastasis. (3) Three patients did not receive therapy of bone metastasis, and died within 6 months. In the other five patients, four are still alive.
The interval between diagnosis of uterine carcinoma and detection of bone metastases is within two years. The most common sites are pelvic bone and vertebrae. Specific pathology type and poorly differentiated carcinomas may be risk factors of bone metastasis. The prognosis of bone metastasis of uterine carcinomas is poor. Treatment of bone metastasis is primarily palliative and may prolong survival.
Zhonghua fu chan ke za zhi 01/2007; 41(12):822-5.