Expression Of Tumor Suppressor Gene ING4in Hydatidiform Mole Is Correlated With Microvessel Density

Objective: Hydatidiform Mole (HM) is one of the GestationalTrophoblastic Disease (GTD), is due to placental trophoblast cell proliferationand edema after pregnancy, divided into Complete Hydatidiform Mole (CHM)and Partial Hydatidiform Mole (PHM). Hydatidiform mole is confined to theuterine cavity, it is benign lesions, but there are certain malignant tendency.CHM occurs probability of locally invasive and distant metastasis is15%and4%, respectively, PHM occurs locally invasive probability is2%to4%.Therisk factors of local invasion and (or)distant metastasis of HM:1.age>40years;2.the serum HCG>100,000U/L;3.the uterus significantly greater thanthe corresponding weeks of gestation;4. luteinized cyst diameter>6cm;5.repeated hydatidiform.The pathogensis and mechanisms of malignanttransformation of hydatidiform mole is unclear, so need furtherstudy.Development from hydatidiform mole, invasive mole and intochoriocarcinoma is likely to be a different stage of the disease.Two categoriesof genes including proto-oncogenes and tumor suppressor genes are mainlyinvolved in the process of tumorigenesis and development.The tumorsuppressor gene is an important factor defensing tumorigenesis in the body.Imbalance of their regulation would lead to the tumorigenesis.The ING4genebelongs to the inhibitor of growth tumor suppressor family. ING4gene plays aspecific anti-tumor effect through multi-channels, it is a potential new tumorsuppressor gene due to its role in the inhibition of cell migration,cellcycle,andinduction of apoptosis,tumor angiogenesis. Occurrence and development oftumor is closely related with neovascularization. Microvessel density (MVD)is the gold standard to evaluate angiogenesis in solid cancers. In the study ofovarian cancer tissues, Yinglanliu etc.found ING4protein expression wassignificantly lower in ovarian cancer tissues compared to normal controls. ING4protein expression was negatively correlated with the MVD.There is norelated literatures about whether ING4gene play a role in the pathogenesis ofhydatidiform mole and what role,so this experiment intendes to detectexpression of ING4gene and microvessel density through immunohistochem-istry in hydatidiform mole and to explore the relationship between them andthe clinical significance.Methods:Immunohistochemical PV method were performed to searchfor the expression of the ING4protein and microvessel density in the tissuesof normal chorion of early gestation and hydatidiform mole.Experimentalgroup:30cases(including14cases of complete hydatidiform mole and16casesof partial hydatidiform mole, three cases of HM malignant transformation, norisk factors is five cases, with high-risk factors is25cases of. age≤40years is23cases,age>40years is7cases; serum HCG≤100,000mIU/ml is9cases>100,000mIu/ml is21cases,; uterus size:≤gestational age is the16cases>gestational age is the14cases; repeatable the hydatidiform history is twocases), control group:20cases of normal chorion of early gestation. Determi-ntion of experimental results: ING4protein expression judgment: Nucleusand (or) intracytoplasmic brown particles,established a semiquantitative scorecorresponding to the sum of both the staining intensity (0, negative;1, weak;2,intermediate;3, strong) and the percentage of positive cells (0,0%positivecells;1,1–25%positive cells;2,26–50%positive cells;3,>50%positivecells).The sum of the staining intensity scores and the percentages of positivecells.A score>2represented a positive immunohistochemical survey,≤2represented a negativeimmunohistochemical survey.Results:1The expression of ING4proteins in the normal chorion of earlygestation and hydatidiform mole: The expression of ING4protein were seen inall the chorion of early gestation.Positive rate of ING4protein expression is100%in the chorion of early gestation, Positive rate of ING4proteinexpression in the hydatidiform mole is50%,difference was statisticallysignificant (P <0.05), expression of ING4protein in hydatidiform mole weresingnificantly lower than that in the normal chorion of early gestation. Expression of ING4protein was not statistically significant between theComplete hydatidiform mole and partial hydatidiform mole (P>0.05).2The relationship between the expression of ING4protein and thedifferent risk factors of the hydatidiform mole: Expression of ING4protein intissues of no risk factors and risk factors were lower than that of the normalchorion of early gestation.There was significant difference between the twogroups (P <0.05). There were no significant difference of ING4proteinexpression between the no risk factors tissues and risk factors tissues(P>0.05). Single factor analysis showed that, the ING4protein expression of inhydatidiform mole was not correlated with age,the serum level of HCG,uterine size,and repeated hydatidiform mole (P>0.05).There was3casesmalignant transformation of30hydatidiform mole, malignant transformationrate of10%, three cases of malignant transformation by ING4proteinexpression were negative, non-malignant transformation group ING4proteinexpression rate of52%, with non-malignant group ING4protein expressioncompared to show a downward trend, but no significant difference (P>0.05).3The detection of MVD in normal chorion of early gestation and inhydatidiform mole: Microvascular density (MVD) in the CD34positive caseswas seen in the normal chorion of early gestation and in hydatidiform mole.Microvascular density (MVD)in hydatidiform mole group is lower than that innormal chorion of early gestation, there was significant difference between thetwo groups (P <0.05). MVD in normal chorion of early gestation group ishigher than that in partial hydatidiform mole group, MVD in partialhydatidiform mole group is higher than that in complete hydatidiform molegroup, compared to the three groups, pairwise differences were statisticallysignificant (P <0.05). MVD values of three groups by the ascending order:normal chorion of early gestation, partial hydatidiform mole, completehydatidiform mole.4.The relationship between the Microvascular Density(MVD) and the different risk factors of the hydatidiform mole: Single factoranalysis showed that, the Microvascular density (MVD)of in hydatidiformmole was not correlated with age,the serum level of HCG,uterine size,and repeated hydatidiform mole (P>0.05). MVD of malignant group was5.00±2.65, non-malignant group MVD was3.15±4.62, compared to the malignantgroup and the non-malignant group MVD values show a higher trend,but notstatistically significant (P>0.05).5.The correlation between the expression ofING4protein and MVD in hydatidiform mole: both had positive correlation,the correlation coefficient r=0.137, the correlation is little, no statisticalsignificance (P>0.05). The correlation between the expression of ING4protein and MVD in malignant transformation hydatidiform mole，both hadnegative correlation r=-0.764, but no statistical significance (P>0.05).Conclusion:1The downregulated expressionof ING4protein is involvedin the pathogenesis of hydatidiform mole.2ING4protein expression was notassociated with clinical risk factors.3The downregulated MVD of inhydatidiform mole is involved in the pathogenesis of hydatidiform mole.4ING4protein expression had no correlation with MVD in hydatidiform moletissue.