Serum YKL-40 Level And Clinical Significance In Gestational Trophoblastic Tumor

Objective: Gestational trophoblastic tumor/neoplasia (GTT/GTN) is a group of gynecological malignant tumors from placental trophoblast cells, including invasive mole, choriocarcinoma and placental site trophoblastic tumor (PSTT). American Institute of Gynecology and Obstetrics named it as malignant gestational trophoblastic disease in 2004. Invasive mole and choriocarcinoma have many commons in clinical manifestation, diagnosis, therapeutic principle and can be healed by chemotherapy, so International Federation of Gynecology and Obstetrics (FIGO) named invasive mole and choriocarcinoma as gestational trophoblastic tumor/neoplasia in 2000, and made PSTT as a special category correspondingly. The patients who have invasive mole and choriocarcinoma are the main objects about this research. The mainly clinical manifestations of invasive mole are irregular bleeding, hysterauxesis or some pseudopregnancy symptoms because of HCG, estrogen and progestogen, such as abdominal pain, theca lutein ovarian cyst. Invasive mole which invasives locally and be accompanied by distant place metastasis in only 4% patient because of its slightly malignant extent has primary lesion in uterus always, with prognosis as well. While choriocarcinoma is the most malignant type in the gestational trophoblastic tumors. It has varied symptoms and signs, and with the evidence of spreading to anywhere outside the uterus by blood at the earlier stage, which the most frequently symptom is pulmonary metastasis. It can be manifested by metastasis symptom instead of primary symptom but high HCG in blood. As reported, 85% patients have pulmonary metastasis when they visited, and there are only 40% have primary lesion in uterus in these patients. There is very poor outcome, and unfortunately, its mortality more than 90% before chemotherapeutics occurred. Human chorionic gonadotrophin (HCG) in blood is the only serology index for the diagnosis and monitoring about prognosis but history, complaint, sign in GTT's diagnosis now. But it has some defects in the early diagnosis of GTT which secondry to normal parturition, especially in the differential diagnosis from ectopic pregnancy and incomplete abortion because the HCG can be secreted by normal gestational trophoblastic cell. YKL-40, a member of the "mammalian 18-glycosyl-hydrolase family", is expressed and secreted by several types of malignant tumors. YKL-40 may plays a important role in cancer cell proliferation, survival and invasiveness, so is in the inflammatory process around the tumor, angiogenesis, and remodeling of the extracellular matrix which are all very important for tumor cell in metastasis. The present clinical studies of YKL-40 suggest that elevated serum YKL-40 is found in a subgroup of patients with different types of solid tumors, including several types of glioblastoma, primary cancer of colon, cervical carcinoma, endometrial cancer, ovarian cancer and breast cancer. The highest serum YKL-40 is detected in patients with advanced cancer and the poorest prognosis. So we can suppose that YKL-40 may be a new biomarker for cancer dignosis and prognosis. But there is no report about YKL-40 and GTT now. We detect YKL-40 levels in the blood of gestational trophoblastic tumor individuals for the detection of early-stage gestational trophoblastic tumor, invasiveness and poorer clinical outcome in this research to make sure if serum YKL-40 can be of value in monitoring patients with GTT and providing information about metastases as a new biomarker.Materials and Methods: The 40 blood specimens of gestational trophoblastic disease were collected from the patients with GTD after being diagnosed by both clinical doctors and pathologic doctors, at the Department of Obstetrics and Gynecology in Number Three Hospital of Hebei Medical University from 2006 January to 2009 January, including 12 hydatidiform mole individuals, 28 gestational trophoblastic tumor patients(24 patients with invasive mole,4 patients subsequently diagnosed with choriocarcinoma). And 8 healthy subjects were as a control. All of the objects must have normal hepatic function, no infection, no operation, no radiotherapy and chemotherapy, no osteopathia and arthropathia, no other tumor history and no anyother treatment before. 3ml venous blood of all of these patients who must be preoperative and before accepting chemotherapy without any food and water was collected in drying cuvette, centrifuged at the rate of 3000r/min for 20minutes before being solidified under room temperature. And then, serum was taken and stored in the refrigerator with–200C. Serum YKL-40 levels were assayed by enzyme-linked immunosorbent assay(ELISA). Statistical analysis was performed using the SPSS version 13.0. Differences between groups were analyzed by the completely random design multitude independent sample rank test. P values less than 0.05 was considered statistically significant.Results:1.The average level of YKL-40 in patients which including hydatidiform mole, invasive mole and choriocarcinoma was lower than that in the healthy subjects, which was considered statistically significant(P<0.05).2.The value of YKL-40 in hydatidiform mole individuals was higher than that in the invasive mole, and the difference between the two groups was statistically significant(P<0.05).3.The difference between hydatidiform mole and choriocarcinoma of the value of YKL-40 was not statistically significant(P>0.05), so was between invasive mole and choriocarcinoma .Conclusion:1. The result that the YKL-40 level in GTD's was lower than that in healthy people suggest that YKL-40 may play a role in the occurrence of the gestational trophoblastic disease.2. And YKL-40 in hydatidiform mole individuals was higher than that in invasive mole patients indicate that YKL-40 may play a role in the occurrence of the invasive mole.3. But there was no statistically significant difference between hydatidiform mole and choriocarcinoma , so was between invasive mole and choriocarcinoma (p>0.05), which manifest that the utility of YKL-40 in the occurrence of choriocarcinoma deserves further research when we get enough samples and make sure the patients have same pregnancy history.