DIFFERENTIAL EXPRESSION OF P57(KIP2), A MATERNALLY IMPRINTED CDK INHIBITOR, IN NORMAL HUMAN PLACENTA AND GESTATIONAL TROPHOBLASTIC DISEASE

Evidence has recently been provided to support a role for genomic impr inting in the regulation of embryonic implantation and development and placental growth, as well as in the pathogenesis of proliferative tro phoblastic diseases. The cyclin-dependent kinase inhibitor p57(KIP2) h as recently been recognized as a maternally imprinted gene. We investi gated p57(KIP2) expression in first-trimester normal placentas from in terrupted pregnancy, spontaneous abortions, and different types of pro liferative trophoblastic diseases using single- and double-marker immu nohistochemical techniques. In normal placenta, nuclear p57(KIP2) expr ession was observed at high frequency (up to 100%) in extravillous tro phoblast, cytotrophoblast, and implantation-site interstitial trophobl ast, but was absent in syncytiotrophoblast. p57(KIP2) was also express ed in the stromal cells of maternal decidua, which was one of the few adult tissues retaining p57(KIP2) expression (most other adult tissues investigated were negative). p57(KIP2) expression was either absent o r low in all cases of diploid/tetraploid complete moles (20 cases) and in three cases of gestational choriocarcinoma. On the other hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases ) showed p57(KIP2) levels comparable to those observed in normal place nta. These findings are in line with the hypothesis that deregulation of genomic imprinting, particularly the loss of cell-cycle inhibitors such as p57(KIP2), is involved in the abnormal development of androgen etic trophoblastic proliferations. In addition, this simple immunohist ochemical analysis could provide a useful diagnostic marker in difficu lt cases.