Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Abstract

The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) -core fragment (hCG cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

Important Role of the Dihydrouracil/Uracil Ratio in Marked Interpatient Variations of Fluoropyrimidine Pharmacokinetics and Pharmacodynamics

“…ANC and HCG/β-HCG levels are the sensitive and representative indexes for predicting main toxicities and efficacy; most important, they can be quantitatively evaluated and are superior to other clinical indexes. [23][24][25] Furthermore, after comparing the clinical efficacy and toxicities between 5-FU and FUDR treatments in GTT patients, no obvious differences were found, which is consistent with the in vitro results. 40 Chemotherapeutic efficacy is normally associated with dose intensity, which is defined as the amount of drug delivered per unit of time, regardless of the schedule used.…”

Direct Analysis of hCGβcf Glycosylation in Normal and Aberrant Pregnancy by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

“…The β 6–40 polypeptide chain contains the two hCGβ N -linked carbohydrate moieties, although the oligosaccharides are truncated due to metabolism. Urinary hCGβcf can be isolated with relatively straightforward procedures [15] from a simple urine sample and offers a convenient way of providing insights into glycosylation of the hCGβ subunit and therefore the hCG from which it was derived [18]. This presents an opportunity to indirectly study pregnancy disorders known to exhibit glycoform variants of hCG.…”

Comparison of human chorionic gonadotropin +β and invasive trophoblast antigen disappearance rates in serum after evacuation of molar pregnancy

“…The question whether ITA is a better marker of PTD than hCG+ß parallels the discussion by Okamoto et al (20) regarding the usefulness of hCG ß-core fragment (hCGßcf) for early prediction of subsequent development of post-molar PTD. These authors reported that, due to its short half-life, serum hCGßcf rapidly declined and became undetectable after evacuation of the mole with subsequent spontaneous resolution.…”