Localization and significance of urokinase plasminogen activator and its receptor in placental tissue from intrauterine, ectopic and molar pregnancies

Urokinase plasminogen activator receptor (uPAR) is a membrane-anchored prot ein with urokinase plasminogen activator (uPA) as the ligand. This complex induces proteolysis and remodelling of maternal decidua during placental im plantation. The presence of uPAR on trophoblasts is supposed to promote adh esion, migration and invasion. In cancer tissue, high levels of uPAR are co rrelated with a poor prognosis. This immunohistochemical study shows the lo calization of uPA and uPAR in a prospective design with stereological sampl ing of fetal and maternal tissue from normal, ectopic and hydatidiform mola r (HM) pregnancies. Cytokeratin and Ki67 were used as markers for trophobla sts and proliferating cells. Membrane-bound uPAR was observed on villous no n-proliferating intermediate trophoblasts (IT) within cell columns in intra uterine and ectopic pregnancies. The corresponding proliferating IT with cy tological atypia sprouting from the chorionic villi in HM was uPAR-negative . uPA but not uPAR was observed in anchoring distal IT at the attachment-po int to the basal plate. In the placental bed, extravillous interstitial tro phoblasts were uPa-positive but uPAR-negative. The trophoblast giant cells were both uPA- and uPAR-negative. In relation to the maternal vessels, a fo cal distribution for uPA and uPAR was present in the endovascular and periv ascular trophoblasts. The intraluminal trophoblasts overlying endothelial c ells were uPAR-positive only. In maternal tissue from intrauterine and mola r pregnancies, uPAR was seen in the decidual cells in a zone facing the anc horing villi and the fibrinoid lesions with embedded trophoblasts. In contr ast, the stromal cells of the fallopian tube without a decidual reaction fa cing the implanted gestation were uPAR-negative. Non-invaded decidual, myom etrial and muscular tissue of the pregnant uterus and fallopian tube was ex tensively positive for uPA whereas 'pseudodecidual' cells from the intraute rine evacuate in patients with an ectopic pregnancy only showed a focal and scanty reaction for uPA. When trophoblast invasion of the decidua was pres ent, the decidual cells were uPA-negative. A semi-quantitative assessment o f the receptor was estimated in villous IT within cell columns in normal an d molar pregnancies but, in conclusion, quantitative evaluation of uPAR can not be used to predict development of post-molar persistent trophoblastic d isease (PTD). (C) 1999 Harcourt Publishers Ltd.