Download 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/