Heterogeneous Distribution of Fetal Microchimerism in Local Breast Cancer Environment

Abstract

Fetal cells enter maternal circulation during pregnancy and persist in the woman’s body for decades, achieving a form of physiological microchimerism. These cells were also evidenced in tumors. We investigated the frequency and concentration of fetal microchimerism in the local breast cancer environment. From 19 patients with confirmed breast neoplasia, after breast surgical resection, we collected three fresh specimens from the tumor core, breast tissue at tumor periphery, and adjacent normal breast tissue. The presence of male DNA was analyzed with a quantitative PCR assay for the sex determining region gene (SRY) gene. In the group of women who had given birth to at least one son, we detected fetal microchimerism in 100% of samples from tumors and their periphery and in 64% (9 of 14) of those from normal breast tissue. The tissues from the tumor and its periphery carry a significantly increased number of SRY copies compared to its neighboring common breast tissue (p = 0.005). The median of the normalized SRY-signal was about 77 (range, 3.2–21467) and 14-fold (range, 1.3–2690) greater in the tumor and respectively in the periphery than in the normal breast tissue. In addition, the relative expression of the SRY gene had a median 5.5 times larger in the tumor than in its periphery (range, 1.1–389.4). We found a heterogeneous distribution of fetal microchimerism in breast cancer environment. In women with sons, breast neoplasia harbors male cells at significantly higher levels than in peripheral and normal breast tissue.

Fetal microchimerism in human brain tumors

“…Given results of previous studies showing increased fetal microchimerism in tumors compared to surrounding normal tissue (10, 32, 35), we wondered whether microchimerism might be similarly increased in brain tumors compared to normal brain. We identified slides that contained brain parenchyma without signs of tumor involvement and used these to assess whether microchimerism prevalence differs in surrounding, apparently normal, tissues.…”

“…The presence of microchimeric cells in blood has been prospectively associated with decreased risk for breast cancer and increased risk for colon cancer (22). In addition, microchimeric cells have been identified in tumors of the breast, lung, thyroid, cervix and skin (7, 10, 13, 32, 33, 35). In these studies, the frequency of microchimeric cells was increased in malignant neoplasms compared to surrounding normal tissue (10, 32, 35) and benign neoplasms (13, 33).…”

Chimerism involving a RB1 pathogenic variant in monochorionic dizygotic twins with twin–twin transfusion syndrome

“…However, they did not identify the familial variant in the tumor tissue of any of the phenocopies. Ultimately, their study did not support their hypothesis (Mitchell et al, 2018).…”

Can chimerism explain breast/ovarian cancers in BRCA non-carriers from BRCA-positive families?

“…Their role in carcinogenesis remains unknown. Some studies suggest their protective role in breast [ 64 , 67 ] and other maternal cancers, while others point towards their unfavorable role in promoting tumorigenesis [ 66 ]. However, so far no studies showed that fetal cells can directly give rise to cancer by forming a malignant clone in a mother, although some research suggests that it is possible [ 68 ].…”