| BackgroundGestational trophoblastic neoplasia(GTN)is a group of malignant diseases that derived from placental trophoblast cells which include invasive mole,gestational choriocarcinoma,placental-site trophoblastic tumor(PSTT)and epithelioid trophoblastic tumor(ETT)[1].GTN can be secondary to the mole,miscarriage,ectopic pregnancy and pre-term labor,of which about 60%comes from the mole[2].Although the researchers have done so much study on it,the mechanism of HM is still unknown.But it is known that genetic,environmental,immune and other factors may play important roles in it.IL-1? is a member of the interleukin 1 family of cytokines,also known as lymphocyte activation factor.It is a pleiotropic proinflammatory cytokine produced by monocytes,macrophages,neutrophils,glandular epithelium and stromal cells in the endometrium[3].This cytokine is an important mediator of the inflammatory response,and is involved in a variety of cellular activities,including cell proliferation,differentiation,and apoptosis.During pregnancy,the growth of the embryo is associated with the production of cytokines from placental trophoblast cells and maternal decidua cells.The relationship between trophoblast cells and maternal immune cells is closely related to the final outcome of pregnancy.Many studies have shown,the production of IL-1? plays an important role on ovulation,placental trophoblast growth,blastocyst implantation and removal of hazardous substances[4.5].Normal growth and development of the embryo depends on normal maternal immune function.In recent years the study of familial recurrent mole discovered that the NLRP7 gene is the cause of recurrent hydatidiform mole.Studies have shown that some patients have mutations in NLRP7 had abnormal expression in IL-1?.The NLRP7 gene with mutations could induce the occurrence of mole by inhibiting the secretion of IL-1?.The occurrence of the disease was depend on the regulation of the inflammatory pathways.However,whether the occurrence of gestational trophoblastic neoplasia which came form the mole had the same mechanism is not clear.Currently,chemotherapy is the primary treatment for GTN.Even there is extensive metastasis,it can still achieve high cure rates through chemotherapy[6].The serum HCG is probably the best single diagnostic after uterine evacuation.Thus,the continuous monitoring of HCG is essential for diagnose and treatment[7].Most patients in GTN have a high lever of serum HCG,but in recent years,we found more and more GTN patients with low levels of HCG.However,the specific mechanism and its clinical features is unclear.Due to the different levels of HCG in patients with various clinical stages,treatment options and its prognosis are different.Compared with patients with low levels of HCG,high levels patients have high tumor burdens and they can not be cleared easily.According to this study,all patients were divided into two groups according to the different level of HCG,to find if there was any differences of clinic features and treatment between patients with different levels of HCG.From the study of the expression of IL-1? in two groups,we can also explore if there is any abnormal expression in IL-1? in two grows and any differences between patients with different levels of HCG.From that,we can find if the patients had abnormal immune functions.Through the study of the above questions,we can have further understanding of the pathogenesis of gestational trophoblastic disease and also provide a reference for the diagnosis and treatment of gestational trophoblastic neoplasia.ObjectiveBy detecting the expression of IL-1? and retrospective analysis of clinical cases of gestational trophoblastic neoplasia with different levels of HCG,we can explore If patients in GTN have abnormal expression in IL-1? and any differences between patients with different levels of HCG.We can also find out the factors of clinical features,diagnoses and treatments between patients in GTN with different levels of HCG.Materials and Methods56 cases of GTN patients admitted in The Hangzhou First People's Hospital of Nanjing Medical University and The First Affiliated Hospital of Zhejiang University between July 2013 and July 2015 were retrospectively analyzed.According to the serum HCG level,they were divided into low-level group and high-level group.Select 10 patients and 10 controls.The patients include 10 GTN patients(5 patients from low-level group and 5 patients from high-level group).All patients have no gene mutations and we took their peripheral blood before chemotherapy.At the same time,we choice 10 cases of women as a control whose growth history is normal with no adverse reproductive outcomes.Two groups of patients were collected 20ml peripheral blood and then isolated lymphocytes.Cultured lymphocytes respectively by LPS stimulation.Collecting the supernatant for the detection of IL-1?.Results1.The expression of IL-1?.Before adding LPS,the expression of IL-1? in low-level group was 359.23pg/ml.After adding LPS,the expression of IL-1? in low-level group was 1209.67 pg/ml.But in high-level group,the expression of IL-1? was 18.40 pg/ml before adding LPS and 1155.10pg/ml after adding LPS.In control group,the results was similar.Before adding LPS,the expression of IL-1? was 30.02 pg/ml.After adding LPS,the expression of IL-1? in low-level group was 1158.39 pg/ml.By comparison we found that the expression of IL-1? in each group was significantly increased after receiving LPS stimulation(P<0.01).Before adding LPS,the expression of IL-1? in low-level group,high-level group and control group was 359.23pg/ml,18.40 pg/ml and 30.02 pg/ml respectively.By comparison between these three groups,there was no significant difference(P>0.05).And after the addition of LPS,IL-1? levels were significantly increased,the concentration of the three groups was 1209.67pg/ml,1155.10pg/ml,1158.39pg/ml,respectively.But by comparison,there were no significant difference between three groups(P>0.05).2.Clinical featuresThe low level group aged 23-55 years,mean age 31.7 years,of which 85.19%of the patients<40 years old,while the high level group aged 18-53 years,mean age 33 years,of which 75.86%of the patients<40 years old.The difference was not statistically significant(P>0.05).Two groups of patients in the last pregnancy outcomes and mole pathology had no significant difference(P>0.05).The interval between antecedent pregnancies and GTN had statistically significant differences between the patients with different levels of HCG(P<0.05).The vaginal bleeding in patients with low levels of HCG were more than that in patients with high levels of HCG,it had significant difference(P<0.05).The distribution of GTN stages had significant difference between two groups(P<0.05)while the prognosis score did not(P>0.05).There was also significant difference in the incidence of lung metastasis between two groups(P<0.05).Although there was no difference in drug resistance happens(P>0.05),the patients with high levels of HCG required more courses of chemotherapy than those with low levels of HCG(P<0.05).Conclusions1.There is no significant correlation between the expression of IL-1? and the occurrence of gestational trophoblastic neoplasia which was derived from mole.And the immune response did not decrease when they received harmful stimulations.2.Patients in GTN with different levels of HCG had a significant difference in the time of onset,clinical manifestations,clinical stage,lung metastases and chemotherapy.Thus,human chorionic gonadotropin is an important indicator of GTN,improving follow-up procedures is important to the early diagnosis and treatment of the disease.To evaluate patients by FIGO stage and the-modified WHO prognostic index score,we can choose appropriate chemotherapy methods and provide reasonable chemotherapy.Also,we should take seriously to comprehensive treatment such as surgery.Only in this way can we improve the curative effect. |
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