Urine Human Epididymis Protein4(HE4) As A Biomarker For The Diagnosis And The Differential Diagnosis Of Ovarian And Endometrial Carcinomas

Objective：Ovarian cancer (OC), endometrial carcinomas (EC) andcervical cancer are the three most common malignant tumors of femalereproductive system. Because of the lack of screening tools for OC patients,their5-year survival rates hover between20%and30%. Serum CA125is themain method which uses in clinical practice, but it is elevated in less than halfof early stage for Epithelial Ovarian Cancer (EOC) and always eleavtes inseveral benign gynecology diseaseas and medical illnesses. Nearly30%of ECpatients, however, did not own the observed symptom such as vaginalbleeding in post-menopause period, and some stage I patients with factorssuch as depth of invasion and lymphovascular involvement would need a moreconvenient method to assess the prognosis. But CA125can only detect10%to20%I stage EC patients and25%relapsed patients without symptom. Humanepididymis protein4(HE4), nearly, is reported as a biomarker of OC and EC.We will measure the serum and urine HE4to assess whether urine HE4canimprove or substitute for the serum HE4, to establish a more convenient, safeand less attacked diagnostic method.Methods:1The double antibody sandwich Enzyme-linked Immunosorbent Assay(ELISA) technique was applied to measure the serum and urine level of HE4.There are30healthy conctrols,68benign diseases,30OC patients and30ECpatients. Serum CA125level was measured in Gynecology laboratory by anelectrogenerated chemilumincence method.2The level of urine HE4is normalized using urine creatine or creatinineclearance rate (Ccr). Made operating characeristic curves(ROC) by usinghealthy and benign disease groups as control and got the cut-off point of urine HE4, urine HE4/urine creatine and urine HE4ccrfor ovarian cancer and EC.4Then all statistical were analysed by SPSS13.0statistical softwarepackage.To compare the serum and urine HE4levels of each group,and toassess the sensitivity, specificity and diagnostic performance for OC and EC.Results:1The CA125and serum HE4level in OCs is significant higher than thelevel in healthy controls, benign diseasesand ECs (p all <0.05), and CA125forovarian cancer has a specificity of73.5%with a sensitivity of94.4%and forEC,has a sensitivityof23.3%at86.7%specificity;and serum HE4for ovariancancer has a specificity of91.8%with a sensitivity of93.3%and for EC,has asensitivityof43.3%at71.4%specificity. There is no significant differentbetween their sensitivity and specificity.The ROC of serum HE4for EC showsthat, with the cut-off point of35.517pmol/L, there is a sencitivity of93.3%and a specificity of84.7%,and the sensitivity is significant higher than that ofCA125(p<0.05).2The level of urine HE4, urine HE4/urine creatine and urine HE4ccrforOcs and ECs are all significantly higher than healthy controls and benigndiseases (p all <0.05). The specificity of urine HE4for Ocs is significant betterthan serum HE4(p<0.05), but the sensitivities are no siginificantdiffernrt(p>0.05). For Ecs, the sensitivity and specificity are both nosignificant different(p all>0.05). There are all significant correlation betweenurine HE4and serum HE4at each group(p<0.05，r=0.631；p<0.05，r=0.349；p<0.05，r=0.852；p<0.05，r=0.982).3Similarly, the best cut-off point of urine HE4,urine HE4/urine creatineand urine HE4ccrfrom ROC are respectively71.519pmol/L、0.920、40.022forovariancancer and38.593pmol/L、0.477、23.181for EC. Correspond to thesepoints, for ovarian cancer, urine HE4has a sensitivity of93.3%at99.0%specificity,and urine HE4/urine creatine has90.0%sensitivity with98.0%specificity,and urine HE4ccrowns93.9%sensitivity and96.9%specificity. Butfor EC, urine HE4gets a sensitivity of83.3%at92.9%specificity, and urineHE4/urine creatine takes83.3%sensitivity with91.8%specificity, and urine HE4ccrhas a sensitivity of77.8%and92.9%specificity.4The diagnostic performance, sensitivity and specificity of urine HE4forOcs and ECs, normalized by urine creatine and Ccr, are not significantly betterthan urine alone(p all>0.05).Conclusion:1The levels of serum HE4elevate significantly at Ocs and ECs, and itdid not increase in the conditions which CA125always elevate, for example,in the pelvic paratubal cyst, ovarian endometriotic cysts and ovarian theca celltumor-fibrous tumor. So serum HE4can improve the specificity of Ocs andEcs.2There is a positive correlation between urine HE4and serum HE4ineach group, and urine HE4’s sensitivities of Ocs are similar for serum HE4,but the specificity is significant better than that of serum HE4.And to EC, thesensitivity and specificity of the two HE4is same.Additional, urine HE4is notcorrelated with urine creatine at each groups,and after normalized, thediagnostic performance, sencitivity and specificity of urine HE4/urinecreatine and urine HE4ccr are not significant better than urine HE4alone. Insummery, the diagnostic performance of urine HE4for ovarian cancer and ECare similar with that of serum HE4,so we can consider it a secondary and a noinjury diagnosis method,and without normalized by urine creatine or Ccr,urine HE4aslo should show excellent performance.