TSPY Expression Identifies Higher-grade Breast Cancer in African American Women: Evidence of Fetal Microchimerism in Tumor Tissue

Fetal cell microchimerism, the presence of genetically distinct fetal cells in maternal tissues, arises naturally during pregnancy when fetal stem cells migrate into maternal circulation. These cells can engraft in damaged tissues, including malignancies, and may play a role in tumor biology. This study evaluated the association between fetal microchimerism—detected through Testis-Specific Protein Y-encoded (TSPY) expression—and clinicopathologic features of invasive breast cancer in African American women. We conducted a blinded case–case study using immunohistochemical analysis of TSPY expression in 202 archival breast cancer tissues. TSPY protein, a marker of microchimeric Y-chromosome DNA, was assessed in relation to clinical and pathological characteristics including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, stage, size, and molecular subtype. Associations were examined using Chi-square tests. Survival outcomes were evaluated using Kaplan–Meier analysis. The results demonstrated that TSPY expression was not associated with patient age, receptor status, or triple-negative phenotype. However, TSPY positivity was significantly associated with higher tumor grade (p = 0.043), suggesting a relationship between fetal microchimerism and more aggressive disease features. Therefore, we concluded that microchimeric TSPY expression is enriched in higher-grade breast tumors among African American women. These findings suggest that fetal cell microchimerism may contribute to—or serve as a biomarker of—advanced breast cancer biology, although its mechanistic role requires further investigation.