Abstract 4375: Cancer protection by pregnancy – a link with microchimeric fetal/maternal stem cells in a stromal niche: Breast cancers are hypochimeric, but the HER2-subtype is hyperchimeric

Abstract

Abstract The PURPOSE of our studies was to investigate the origin and cancer relations of embryonic/fetal stem cells in breast cancer. HYPOTHESIS. During pregnancy the documented exchange of fetal and maternal stem/progenitors establish long-term integration in the recipient organism. We propose that the breast is a potential niche and this new stem cell pool may affect breast cancer. OBJECTIVES. (i) To work out more sensitive methods to detect Y- and X-chromosomal markers from embedded, formaldehyde-fixed tissue samples; (ii) To find the tissue compartment for the long-term microchimerism niche in the breast; and (iii) to collect quantitative chimerism data to investigate non-chimeric, hypochimeric, microchimeric and hyperchimeric contribution to cancer. EXPERIMENTS. We developed new systems for Y-signal detection (single-amplicon/multiple-target analysis) and X-haplotype analysis with significantly increased sensitivity from low-integrity samples. We analyzed 55 normal samples representing stromal, ductal and lobular tissues and 102 invasive ductal breast cancer samples. Quantitative amplifications were performed following recent MIQE recommendations. We used fluorescent in-situ hybridizations (FISH) to confirm microchimerism. The data were analyzed by extensive statistical analyses and only data with statistical significance are presented. RESULTS. We found 19.6% microchimerism in cancer samples, in contrast to 40% in normal tissues. The results confirm that hypochimerism promotes but microchimerism protects from cancer. We show for the first time that the long-term niche for post-pregnancy microchimeric (male) cells is the mammary stroma but they don't integrate into the ducts, the site of most cancers. Based on the findings we propose that breast cancer protection by pregnancy may be a stromal function and involves fetal microchimerism. Unexpectedly, we also found that a cohort of breast cancers show runaway microchimerism with significantly increased male-cell content. This is the first report that hyperchimerism correlates with the HER2-subtype and unfavorable prognosis. CONCLUSIONS. We developed a new assay and our studies demonstrate previously unrecognized significant stromal integration of fetal/maternal stem cells in protection from breast cancer. We also found, however, that excessive microchimerism promotes cancer and correlates with the HER2-subtype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2011-4375