P-Rex1 Expression in Invasive Breast Cancer in relation toReceptor Status and Distant Metastatic Site

Background. Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-Rex1) has been implicated in cancergrowth, metastasis, and response to phosphatidylinositol 3-kinase (PI3K) inhibitor therapy. The aim of this study was to determinewhether P-Rex1 expression differs between primary and metastatic human breast tumors and between breast cancer subtypes.Design. P-Rex1 expression was measured in 133 specimens by immunohistochemistry: 40 and 42 primary breast tumors frompatients who did versus did not develop metastasis, respectively, and 51 breast-derived tumors from metastatic sites (36 of which hadmatching primary tumors available for analysis).Results. Primary breast tumors showed significant differences in P-Rex1 expressionbasedonreceptorsubtype.ER+andHER2+primarytumorsshowedhigherP-Rex1expressionthanprimarytriple-negativetumors.HER2+ metastases from all sites showed significantly higher P-Rex1 expression compared to other metastatic receptor subtypes.Solid organ (i.e., brain, lung, and liver) metastases showed higher P-Rex1 expression compared to bone metastases.Conclusions.P-Rex1 expression is increased in ER+ and HER2+ breast cancers compared to triple-negative tumors. P-Rex1 may be differentiallyexpressed in metastatic tumors based on site and receptor status. The role of P-Rex1 in the development of breast cancer metastasesand as a predictive biomarker of therapeutic response warrants further investigation.