Clinicopathologic profile of gestational trophoblastic disease.
Much debate exists on factors predicting the development of persistent gestational trophoblastic disease (pGTD). Diagnosis is still limited by following persistently elevated or rising postevacutation beta-human chorionic gonadotropin (beta-hCG) titers. The aim of the present work was to evaluate the hypothesis that the presence of c-erbB-2 oncogene amplification and expression, in combination with parameters such as DNA-content and karyotype of the sex chromosomes, confer an increased risk of developing pGTD. Clinicopathological characteristics were evaluated in 36 cases of gestational trophoblastic diseases (GTD) and analyzed for c-erbB-2 amplification and protein p185 expression using differential polymerase chain reaction (DPCR) and immunohistochemical (IHC) techniques. The DNA-content was determined by image analysis on Feulgen stained nuclear cell preparations and karyotyping for XY chromosomes was performed by fluorescence in situ hybridization (FISH). The data was correlated with histopathological characteristics of GTD. Seventy-five percent (n = 27) of the examined cases showed spontaneous regression after evacuation, including 2 patients who received additional chemotherapy. Twenty-five percent (n = 9) resulted in a persistent or metastatic disease. The median time between antecedent pregnancy and GTD was 45.4 months. Complete remission was achieved in all patients with pGTD after administration of chemotherapeutic agents or adjuvant surgical procedures. Cases with cerbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in 2 complete hydatidiform moles with advanced stage and DNA hyperploidy. From these results we conclude that c-erbB-2 amplification and/or protein expression in combination with DNA-content show a significant correlation with the proliferative and aggressive potential of GTD, suggesting their combined use as a possible marker for pGTD.
Jelincic
Darko
D
Division of Prenatal Diagnostics and Therapy, University of Vienna, Vienna, Austria.
Hudelist
Gernot
G
Singer
Christian Fridolin
CF
Bauer
Margit
M
Horn
Lars Christian
LC
Bilek
Karin
K
Czerwenka
Klaus
K
D000293:Adolescent; D000328:Adult; D001317:Austria; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018734:Genes, erbB-2 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D011003:Ploidies; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D014328:Trophoblastic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014594:Uterine Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014599:Uterus / Q000473:pathology
D018997:Chorionic Gonadotropin, beta Subunit, Human; D004273:DNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases