Increased fetal cell microchimerism In high grade breast carcinomas occurring during pregnancy

Abstract

Pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. These cells are able to migrate and differentiate within various damaged maternal tissues. We recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. In this study, we aimed to reproduce these results in a murine model of "pregnancy- associated" breast carcinoma. We bred virgin MMTV-H-Ras transgenic female mice with male mice transgenic for Inciferase under the control of the VEGFR2 promoter. Tumors that developed during or following gestation were analyzed and their nuclear grade classified. Fetal cells were detected by Y chromosome Fluorescence in situ hybridization FISH in 9/9 of breast carcinomas but only in 2 liver controls from the same animals. The number of fetal cells was 20 and 4.9 per million maternal cells in these tissues, respectively (p < 0.05). High grade tumors had significantly more fetal cells (p < 0.05). In vivo imaging of the luciferase signal under control of the VEGFR2 promoter as well as von Willebrand staining did not reveal an endothelial phenotype of fetal cells. Sixty two percent of the fetal cells expressed cytokeratins but were not tumoral. In conclusion, fetal cells - expressing cytokeratin - are always present in murine breast carcinomas associated with gestation. Interestingly, high-grade tumors contain more fetal cells. © 2008 Wilev-Liss, Inc.