Loss of IGF-II imprinting in endometrial tumors: overexpression in carcinosarcoma

The genomic imprinting of the maternal allele defines the monoallelic expre ssion of the IGF-II gene in most human tissues. The loss of imprinting (LOI ) leading to biallelic overexpression of IGF-II has been reported in severa l human malignancies, including uterine leiomyosarcoma. To ascertain if LOI occurs in endometrial malignancies, the allelic expression of the IGF-II g ene was examined in samples of normal human endometrium (n = 22) and endome trial tumors (n = 12) by assessing the ApaI polymorphism in cDNA segments a mplified by RT-PCR. The biallelic overexpression of IGF-II mRNA, involving activation of all four (P1-P4) promoters, was detected in one normal endome trium and in one endometrial carcinosarcoma. Low level biallelic expression of IGF-II was also detected in two samples of hormone-unresponsive/Type II endometrial carcinomas. The level of IGF-I mRNA in these four samples was low. The IGF-IR mRNA was overexpressed in all endometrial cancers including the carcinosarcoma sample, but not in normal endometrium. These data sugge st that LOI associated with overexpression of IGF-II and concomitant overex pression of IGF-IR may play a role in the rare carcinosarcoma of the endome trium. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.