The Expression Of HE4in Serum Of Patients With Endometrial Carcinoma And The Clinical Value Of Combined Detection With CA125

Objective: To detect the levels of serum HE4and CA125in patients with normalendometrium, endometrial atypical hyperplasia and endometrial carcinoma(EC). Toanalyze the relationship between the levels of serum HE4and differentclinicopathological parameters of endometrial carcinoma. To explore the role of HE4in the occurrence and the development of endometrial cancer and the clinical value ofcombined detection of HE4and CA125.Methods: The serum levels of HE4and CA125were tested by an chemiluminescentmicroparticle immunoassay(CMIA) method.65patients were devided as follows:15specimens of normal endometrium,10specimens of endometrial atypical hyperplasia,40specimens of endometrial carcinoma. We made operating characeristic curves(ROC)by using patients with endometrial atypical hyperplasia and normal endometrium ascontrol and got the cut-off point of HE4. The evaluation indexs of serum HE4werecalculated in the early diagnosis of endometrial cancer and the correlation of HE4andCA125was analyzed. All statistical analyses were performed with SPSS17.0statisticalsoftware package.Results:(1)High expression of HE4was in the serum of patients with endometrial cancerThe range of serum HE4levels in the normal endometrium group were27.7～84.0pmol/L, with an average of40.3±16.2pmol/L; The range of serum HE4levels inthe endometrial atypical hyperplasia group were41～83pmol/L, with an average of54.7±18.5pmol/L; The range of serum HE4levels in endometrial cancer group were33.9～1040.9pmol/L, with an average of120.2±195.6pmol/L. The levels of HE4inEC group were significantly higher than that in the normal endometrium group, with asignificant difference (Z=-3.444，P=0.01<0.05). The serum levels of HE4in EC groupwere higher compared with endometrial atypical hyperplasia group, the difference was not significant(Z=-0.845，P=0.398>0.05). The serum levels of HE4in endometrialatypical hyperplasia group were higher compared with normal endometrium group, thedifference was also not significant(Z=-1.859，P=0.063>0.05).(2) The levels of serum HE4were correlated with the progression of endometrialcarcinomaThe levels of serum HE4of patients with endometrial cancer were not correlatedwith ages, histological grades and pathological types (Z=-1.671, P=0.095>0.05;Z=-1.569, P=0.117>0.05; Z=-1.155, P=0.248>0.05); While it had positive correlationwith surgical-pathologic stage, depth of myometrial invasion and lymph nodemetastasis (P<0.05). The later the higher levels of serum HE4in EC. The levels ofserum HE4in patients of EC with clinical stage Ⅲ-Ⅳ were higher than the patients ofEC with clinical stageⅠ-Ⅱ(Z=-2.583，P=0.010<0.05); The levels of serum HE4inpatients of EC with deep myometrial invasion were significantly higher than thepatients of EC with superficial myometrial invasion(Z=-2.500，P=0.012<0.05); Thelevels of serum HE4in patients of EC with lymph node metastasis were significantlyhigher than the patients of EC with non lymph node metastasis(Z=-3.088，P=0.002<0.05).(3) HE4exhibited better than CA125for early diagnosis of endometrial cancerOperating characeristic curve(ROC)were made by using patients with endometrialatypical hyperplasia group and normal endometrium group as control, the cut-off pointof HE4was received. A serum HE4level of58.6pmol/l had the most significantdiagnostic index (0.436), with a sensitivity of59.6%, a specificity of84%, a positivepredictive value of84.6%, a negetive predictive value of58.3%and a diagnosticaccuracy was69.4%. The ROC area under the curve of HE4was0.719. When CA125threshold was set at35U/ml, we got a sensitivity of21.6%, a specificity of76%, apositive predictive value of57.1%, a negetive predictive value of39.6%, a diagnosticaccuracy of43.5%and the ROC area under the curve was0.535. The sensitivity andthe specificity of combined detection of HE4and CA125for diagnosing EC were64.9%and74.3%. As a single tumor marker, HE4performed the better in ECcompared with CA125. Combined detection of HE4and CA125was better than anyindividual detection. (4) The levels of serum HE4and CA125in patients with endometrial cancer showedno correlationAnalysis of the levels of serum HE4and CA125in patients with endometrialcarcinoma revealed that there was no correlation between the levels of serum HE4andCA125(r＝0.207，p＝0.218).Conclusion:(1)The expressions of serum HE4in patients with normal endometrium, endometrialatypical hyperplasia and endometrial carcinoma gradually increased. The levels ofserum HE4in patients of EC were higher than normal endometrium and endometrialatypical hyperplasia. which was expected that HE4may be related to the occurrence ofendometrial cancer.(2)The levels of serum HE4in patients with endometrial cancer were not correlatedwith ages, histological grades and pathological types while it had positive correlationwith surgical-pathologic stage, depth of myometrial invasion and lymph nodemetastasis, which revealed that there was correlation between the levels of serum HE4and the development of endometrial cancer.(3) Tumor marker of HE4performed the better in EC when compared with CA125,which provides the basis for early diagnosis of EC at the molecular level.(4)The combined detection of HE4and CA125was better than any individualdetection.(5)There was no correlation between the levels of serum HE4and CA125inendometrial carcinoma, maybe they were two separate events in development ofendometrial carcinoma.