Research Of The Relationship Between The Pathologic Type And Differential Diagnosis Of The Ovary Cancer By Using The Combined Detection Of HE4and CA125

Object The aim of this study was to find out the value of the single detection and combined detection of HE4、CA125in the differential diagnosis of the ovary cancer and the disease sequelae; to find out the relationship between the level of HE4in serum and the pathologic type of the ovary cancer and its correspondence to the cancer staging and lymphatic metastasis, to test and verify the application value of the non invasive test used in the detection of HE4in the serum during the early stage of the ovary cancer.Method1.The electrochemical luminescence method was used to detect the level of HE4and CA125in the serum, in which60clinical cases were the malignant ovary tumors,10clinical cases were the borderline ovarian tumors,42clinical cases were benign ovary tumors,40clinical cases were benign diseases,26clinical cases were other malignant gynecologic tumors,40clinical cases were normal women.The distribution features of HE4and CA125was statistically analyzed by comparing two by two in order to point out the variance between every group.2.Electrochemical luminescence method was used to detect the level of HE4and CA125in serum in complete followed up12clinical cases of ovary cancer during the preoperative and postoperative periods, a retrospective analysis of the relationship between HE4and C125in serum and the clinical devolution of the tumor was done.3.The patients with the ovary benign tumors,the ovary benign diseases, the healthy women and the healthy women were the population of reference in order to draw ROC curve, to obtain the limit point of the diagnostic value of the serum HE4, to analyze the sensitivity and specificity of the HE4in the serum for diagnosing the ovary cancer, to find out the value of the single and combined detection of HE4and CA125in diagnosing the malignant tumor and diseases of the ovary。4.The immunohistochemistry method was used to detect HE4expression in the patient who have the malignant tumor of the ovary, the borderline ovarian tumors, the benign tumor of the ovary, the benign diseases of the ovary, the normal tissue of the healthy women in order to compare the level of expression variability in every group and the relationship between the pathologic type of the malignant ovary tumor in different stages; to find out the significance of the development of the ovary cancer and the relationship between the preoperative serum HE4in a malignant ovary cancer patient and the intensity of histologic expression。5.Analyze the patients who have the high serum HE4and the corresponding expression of HE4in the ovary tissues and calculate its positivity and negativity.By using the same method we evaluate the conformity ratio of serum HE4to the clinical diagnosis.6.The statistical analysis was done by using the software SPSS13.0.The level of HE4and CA125is indicated by the median number (M), the pathologic diagnosis is considered as the standard one’s, the curve ROC was traced, the sensitivity and specificity were calculated。The multigroup comparative analysis was done by using the non parameter Kruskal-Wallis test, the two by two comparative analysis was done by using Mann-Whitney test。The test precision=0.05。Results1.In the patient who have the malignant tumor of the ovary, the borderline tumor of the ovary, the benign tumor of the ovary, the benign disease of the ovary, other gynecologic malignant tumors and in healthy women, the HEA4level variance in different group of patients has the statistical significance,(P<0.0001); in the goup of the ovary malignant tumor there was a marked variation when compared to other groups, which lead to the statistical meaning。In the other5groups compared by using the two by two method, we did not find out any statistical meaning(P>0.05)。The the variance of CA125level in the serum in different groups has the statistical meaning (x2=61.579, P<0.0001), in the group of malignant ovary cancer the level of expression was markedly elevated than in other groups, which means that the differences is statistical meaningful, but in the group of the ovary benign diseases the level of CA125is high if it is compared to the ovary benign tumor group, the difference also has the statistical significance(P<0.01)。If we compare the population of patient who has the benign tumor of the ovary, the benign disease of the ovary, and the heathy women, when the HE4in serum is56.37pmol/L, the HE4for diagnosing the ovary malignant tumor ROC-AUC is0.858, its sensitivity is80%, its specificity is96%。In the healthy women population group, when the level of HE4in serum is27.18pmol/L, HE4for diagnosing malignant ovary tumor ROC-AUC is0.890, sensitivity is84%, specificity is90%。2. In the group of ovary malignant cancer, the clinical cases in which33%of CA125was negative,60.9%of those cases HE4was positive。In the group of the ovary benign diseases,85.0%of CA125was positive and in92.0%of those cases the serum HE4was negative.in correspondence to the cases in which serum HE4was negative。In the combined detection of HE4and CA125, the sensitivity of the diagnosis for the malignant tumor in the population which has the benign tumor other gynecologic diseases and normal women can reach86.96%3. The serum HE4in the malignant ovary cancer during the preoperative periods is not related to the patient age,(ρ=0.152, P>0.05, P=0.264),the level of HE4in serous ovary cancer compared to the mucinous ovary cancer, the difference has a statistic meaning(Z=-2.12, P<0.05). The HE4level and the pathologic differentiation has the negative relativity ρP=-0.424, P=0.001);with the clinical staging it has the positive relativity (ρ=0.454, P<0.0001)o In the patient who undergo the whole staging of the ovary cancer after the operation,the variance has a statistic significance. The detection of serum HE4in the patients who undergo effective chemotherapy, when the patient clinical status was improved, the serum HE4was decreased as well.When the disease relapse, the serum HE4was increased too.4. HE4expression in serous ovary cancer is higher than the expression mucous ov ovary malignant tumor, borderline ovary tumor, ovary benign tumor, ovary benign diseases(ovary endometriosis cyst)and in the normal tissue of the ovary, the ratio of positivity expression is respectively the following83.3%(50/60)、70%(7/10)、11.9%(5/42)、15.4%(4/26)、0%(0/10)。In the group of malignant tumor and borderline tumor, the ratio of positivity expression was remarkably higher than in other3groups (χ2=44.980, P<0.0001),The malignant tumor and borderline tumor group comparison does not have a statistic significance (χ2=0.390, P=0.533), but the expression intensity of malignant tumor is higher than the borderline tumor group。In the group of normal ovary compared to the benign diseases of the ovary, ovary benign tumor group; ovary benign diseases compared to the ovary benign tumor group two by two, the difference found does not have a statistic significance (P>0.001). The HE4in the serous ovary cancer,mucinous ovary cancer,hyaline cell cancer, ovary adenoendometriocarcinoma、corpus luteum cyst tumor,germ cell tumor, the ratio of positivity expression was respectively100%(30/30)、61.5%(8/13)、66.7%(2/3)、100%(6/6)、25%(1/4)、75%(3/4)。HE4expression in serous ovary cancer was higher than serous the expression in mucinous ovary cancer, so the variance has the statistic meaning(χ2=5.000, p<0.05); In the ovary endometriocarcinoma the expression was higher, hyaline cell cancer and germ cell tumor the intensity of expression was moderate,in the corpus luteum cyst the expression was low。In the tissue of the early stage ovary malignant tumor (Ⅰ/Ⅱ stage) it was lower than the later stage of ovary malignant carcinoma tissue (Ⅲ/Ⅳstage)positivity expression (x2=16.8, p<0.05); in the high differentiated tissue HE4positivity expression was lower than in the low differentiated tissue positivity(x2=10.231, p<0.001);In the patient without the metastatic cancer to other organs tissues,the positivity expression was lower than the positivity expression found in the patient with the metastatic cancer to other organs tissue (χ2=7.459, p<0.05). The level of HE4in the serum and the HE4expression in the tissue are positively linked.5.In Ovary malignant tumor group,50/60clinical cases has a positive HE4expression, in which45cases the detection of HE4in the serum was positive,5cases was negative, including2cases of mucinous ovary cancer,3cases of germ cell tumor.In the borderline tumor group,7/10cases tissues express positively HE4in their serum, in which the whole corresponding HE4was expressed positively。In benign tumor group,5/42cases tissues were expressed positively, the corresponding two cases of mucous cyst-adenoma were negative, In the ovary benign diseases group, the HE4in4/26cases tissues were expressed positively, in the corresponding2cases the serum HE4was negative, the case was the ovary endometriosis cyst.There are2cases of ovary mucinous cancer,1case of borderline ovary mucous tumor,2cases of ovary serous cyst-adenoma and1case of ovary endometriosis cyst in which the serum HE4was positive, the corresponding tissue did not express HE4。Conclusion1. The sensitivity and specificity of HE4in the diagnosis of the ovary malignant tumor is higher than CA125, and the sensitivity is markedly elevated when HE4is detected simultaneously with CA125.The levels of serum HE4were no correlation with age,but were closely related to histological type of ovarian cancer and clinical stage.2..In epithelial tumor of ovary,the HE4expression was significantly increased, but in the mucinous ovary cancer and the ovary germ cell tumor the level of HE4expression was low,even unexpression.There was a positive correlation between the level of HE4in serum and the expression of HE4in the tissue3. HE4highly expressed in epithelial tumor of ovary. The level of HE4in serum and the expression of HE4in the tissue are positively related,which can be change with clinical course.So HE4can be used as a ideal tumor marker to detect the ovary malignant tumor.