The Clinical Significance Of Hyperglycosylated HCG In Gestational Trophoblastic Diseases And 21-trisomy Syndrome

Human chorionic gonadotropin(hCG) is a glycoprotein hormone that is produced by trophoblast tissue of placenta in pregnancy, and multiple hCG-related molecules are present in pregnancy serum and urine samples, these include regular hCG , free a-subunit, free p-subunit, hCG missing p-subunit C-terminal peptide, hyperglycosylated hCG, and urine p-core fragment. The levels of these forms hCG- related molecules are mostly related to pregnancy, pregnancy-related disease, and some poorly differentiated cancers. Such as: urine p-subunit to detect early pregnancy, regular hCG to monitor pregnancy, free p-subunit to help to diagnose or monitor trophoblast disease and other non-pregnancy malignancies as testicular cancer, germ cell tumor.Recently, out of country many researchers are increasingly concern to the hCG- related molecule—hyperglycosylated hCG(HhCG), and put forward to that HhCG may be an effective marker of many pregnancy-related diseases, such as being applied to predicting early pregnancy loss, preeclampsia, management of gestational trophoblastic diseases, and in screening for 21-trisomy syndrome pregnancies, etc. HhCG is invasive, also called invasive trophoblast antigen (ITA), and is secreted by undifferentiated and part-differentiated cytotrophoblast cells. Because of its invasive trait, HhCG probably makes the cytotrophoblast cells more invasive, so the level of HhCG shows the degree of proliferation of trophoblast cells. In common diseases about pregnancy as gestational trophoblastic diseases(GTD), 21-trisomy syndrome pregnancies(Down syndrome,DS), early pregnancy loss, preeclampsia, cytotrophoblast cells abnormally proliferated, or poorly differentiated, or produce low level HhCG, resulted in higher or lower HhCG levels, so measurement of serum or urine HhCG may be useful to diagnose or monitor even predict the occurrence and development of diseases. It is shown that HhCG offersclinical chemistry a new and extended scope beyond hCG in management of pregnancy and pregnancy-related diseases. Now, there is no study on HhCG in our country, this study followed aims to investigate the performance and importance of HhCG as a promising marker in gestational trophoblastic diseases(GTD) > 21-trisomy syndrome pregnancies(DS) of our people.Objective:1> To find out whether serum HhCG is more produced in gestational trophoblasticdiseases, and understand how HhCG varies from the pathological change oftrophoblast cells. 2^ To verify whether maternal serum levels of HhCG in 21-trisomy syndrome ishigher than normal pregnancy, and evaluate the screening performance in prenataldiagnosis.Methods:1> Measurement of HhCG: HhCG was measured by a fully automated chemiluminometric assay on the Nichols Institute Diagnostics with a biotinylated HhCG-specific monoclonal capture antibody (B152), and an acridinium—ester-labeled, anti-hCG (i monoclonal antibody (B207). The generation "flash" of light was detected and quantified, then was directly proportional to the concentration of HhCG.2> Measurement of F-p-hCG: Wallac fully automated immunoassay.3^ Measurement of total hCG: DPC Immulite assay.Results:Part I HhCG and gestational trophoblastic diseases1, Serum of 33 hydatidiform mole cases( no cure), 26 gestational trophoblastic tumor (GTT) cases (from hydatidiform mole) and 55 normal pregnancy controls(8-12 weeks) was collected, and the levels of HhCG, F-|3-hCG ^ total hCG of these cases were detected. As well, HhCG /total hCG> F-p-hCG/totalhCG were calculated. It was shown that HhCG /total hCG, F-0-hCG/total hCG in hydatidiform mole and GTT were both significantly higher than in normal pregnancy(p<0.001);HhCG/total hCG , F-p-hCG/total hCG in GTT were significantly higher than in hydatidiform mole(p<0.005, p<0.001);HhCG/total hCG was significantly higher than F-p-hCG/total hCG in GTD (p<0.001). 2, HhCG of 32 hydatidiform mole cases in hospital was positive correlative to pathological change, the ratio of HhCG: total hCG rose when the trophoblast cells more proliferated. 3 of 32 cases developed from hydatidiform mole to GTT, when diseases were malignant, HhCG: total hCG rapidly rose;but, the HhCG: total hCG in GTT was no certain correlation to stages explained by Peking Union Medical College Hospital in 1962.Part II HhCG and 21-trisomy syndrome prenatal diagnosis1 , Maternal serum of 17 DS, 98 unaffected pregnancies between 15 to 20 weeks of gestation was collected and HhCG concentration was detected. It is shown that the median HhCG in 17 DS was 10.1 IMoM, almost 3 multiples higher than 3.55 MoM, the median of 98 normal cases. And,115 cases were divided three groups on the basis of the result of AFI\ F-P-hCG: DS, high-risks low-risk normal population. The data of HhCGMoMs fit a logarithmic gaussian distribution in three groups, t-test shows HhCGMoMs in DS were higher than high-risk, low-risk normal cases(p<0.02, p<0.001).2, There were 2 DS patients that AFP, F-p-hCG screening showed false-negative(the risks of DS were respectively 1/860, 1/1000), but their HhCGMoMs were respectively 7.5, 10.11, both more than 2.9, the 95th centile of normal pregnancies at 5% false-positive rate that was the result of study by Pandian R and his colleagues in. 2004. If the screening in combination with HhCGMoM, the 2 patients would be shown high risk of DS.Conclusion:HhCG and gestational trophoblastic diseases1 ^ Serum HhCG rose obviously in gestational trophoblastic diseases comparing to the same period normal pregnancy, and the secretion of serum HhCG was positive correlation with the pathologic changes of diseases, when diseases deteriorated, serum HhCG rose sharply. So the measurement of HhCG can be used in diagnosing and managing gestational trophoblastic diseases (GTD).2^ F-p-hCG also rose especially in gestational trophoblastic diseases (GTD), and it can be helpful to diagnose GTD. But comparing to HhCG, the secretion of F-p-hCG in GTD was lower apparently. In GTD, even though F-(i-hCG rose, but the ratios of F-p-hCG: total hCG were generally <5%, while the ratio of HhCG: total hCG was even >50%. Therefore, HhCG rather than F-p-hCG is a more sensitive and effective maker in management of gestational trophoblastic diseases (GTD).HhCG and 21-trisomy syndrome prenatal diagnosis1-, Maternal serum HhCG in 21-trisomy syndrome (DS) is higher than the same period normal pregnancy;it shows the potential usefulness of serum HhCG in detecting 21-trisomy syndrome (DS).2> the measurement of HhCG in combination with AFP> F-p-hCG would improve detection rate and reduce false-negative rate.