Transcript hCG Family
hCG Family; hCG and sister molecules Middle East and Turkish Gynecologic Oncology Joint Meeting Feb. 27-28, 2016, Ankara, Turkey Dr. Müge HARMA Bülent Ecevit University, Medical Faculty, Zonguldak, Turkey [email protected] hCG Glycoprotein α-subunit 92 amino acids ß-subunit 145 amino acids 19 6 Five different hCG structures –five sisters • Common α-subunit and β • hCG α has one gene on chromosome 6 (6q14-q21) • hCG β is represented by 8 genes on chromosome 19 Sisters of St. Anne-Bethany Sr. Ana Clara, OSA, Mother Superior Sr. Maria Agnes, OSA Sr. Maria Teresa, OSA Sr. Olga, OSA Sr. Felicitas, OSA http://www.osa-bethany.org/ Kim, Khloe, Kendall, Kylie Jenner and Kourtney Kardashian http://www.vintageimages.org/index.php/Ladies-CabinetCards/Vintage-Ladies-Cabinet-Cards-39 hCG variants hyp-hCG = sweet hCG hCG vs. hyp-hCG Source Structure Function hCG hyp-hCG Syncytiotrofoblast Cytotrofoblast Trisaccharides Hexasaccharides Corpus luteum progesterone effect Minimal progesterone effect trophophoblast invasion and tumorogenesis (by blocking TGFβ) hCG β and hyp-hCG β –the cancer promoters hyp-hCG –the invasion promoter • Mostly hexasaccharide • Molecular weight 42800 • Blocking apoptosis • Antagonist of TGF Beta receptor • Acts on choriocarcinoma cells promoting invasion and growth Persistent low hCG positivity (%10) (%41) (%42) (%7.6) Khanlian SA, Cole LA. J Reprod Med ,2006 False positive hCG (Phantom hCG) • No history of trophoblastic disease • No direct physical evidence of a tumor False positive serum hCG (Phantom hCG) • Commonly due to interfering heterophilic antibodies (anti-animal antibodies ) • Serum positive for total hCG but urine totally negative (large molecules and do not enter into urine) • If the assay is not properly protected with serum or access non-spesific antibodies, heterophilic antibodies, which are bivalent, will link the two antibodies, just as hCG is meant to do. This causes a false positive results • Total hCG false positive range from 6-1100 mIU/ml False positive results were identified by the following criteria; • The finding of more than 5-fold differences in serum hCG results with alternative immunoassays • The presence of hCG in serum and absence of detectable hCG or hCG or hCG related molecule immunoreactivity in a parallel urine sample • The observation of false positive results molecules not normally present in serum, such as urine b-core fragment • The finding that a heterophilic antibody blocking agent prevented or limited false detection • The finding that hCG results differ greatly when tested undiluted and diluted with serum Phantom hCG Transient decrease of hCG The transient decrease may be due to an interim weakening of the immune system as a result of chemotherapy or surgery This could reduce circulating antibody concentration, leading to decreased false hCG results Quiescent Gestational Trophoblastic Disease (Inactive GTD) • Persistently low level of hCG in the absence of any clinical or radiological evidence of GTN • Usually hCG level is in the range of 50-100mIU/ml and remains static for at least 3 months • It is associated with prior history of GTD or spontaneous abortion and does not respond to therapy • The slow-growing syncytiotrophoblast cells produce small stable amounts of hCG and do not usually progress to invasive disease as long as cytotrophoblast or intermediate cells, are absent • These syncytiotrophoblast cells do not respond to chemotherapy, and surgery does not result normalization of hCG Management of quiescent GTD • During the quiescent period, the patient has no detectable hyp-hCG, but as soon as the hCG rises , a significant proportion is hyp-hCG, and this is found frequently prior to the appearance of clinically detectable neoplasia. • As this time therapy is effective • However this approach is only feasible if the hyp-hCG assay is readily available and affordable • Therefore, it is essential that treatment be individualized and preferably patients with GTN should be managed in centers with dedicated specialists Needless Treatment Needless Treatment No Hyp-hCG kit Management of Quiescent GTD –How ? suggested Charing Cross 345 IU/L USA hCG Reference Service 3000 IU/L FIGO Cancer Report, Trophoblastic disease, 2012 Sulfated hCG a pituitary hormone –Pituitary hCG • This hCG was shown in 1980 to be coming from the pituitary gland • Variant of hCG is made by pituitary gonadotrope cells during the normal menstruel cycle • Analogous to the secretion pattern of LH • hCG and LH both bind a joint receptor, the hCG/LH receptor Pituitary hCG and menopause • Non-pregnant menstrual women >55 years age is <2 to 13.1mIU/ml • Non-pregnant menstrual women 18-40 years age <2 to 4.6mIU/ml • Potential perimenopause women <2 to 7.7 mIU/ml • In the USA hCG Reference Service experience; • hCG levels as high as 29 mIU/ml, median 7.2 mIU/ml are detected in perimenopause and, • as high as 33 mIU/ml, median 8 mIU/ml are detected in menopause Pituitary hCG The detection of hCG in blood after menopause often creates confusion in physicians unaware of the normal pituitary production of hCG which can lead to the erroneous assumption of malignant disease hCG assays hCG Assays FIGO Cancer Report, Trophoblastic disease, 2012 hyp-hCG hCG H elisa kit :: Hyperglycosylated Human chorionic gonadotropin ELISA Kit http://trofoblast.org.tr/ Teşekkürler… http://www.worldcongressgtd2017istanbul.com http://ijtd.org/