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

Abstract EN

Background.

Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-Rex1) has been implicated in cancer growth, metastasis, and response to phosphatidylinositol 3-kinase (PI3K) inhibitor therapy.

The aim of this study was to determine whether 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 from patients who did versus did not develop metastasis, respectively, and 51 breast-derived tumors from metastatic sites (36 of which had matching primary tumors available for analysis).

Results.

Primary breast tumors showed significant differences in P-Rex1 expression based on receptor subtype.

ER+ and HER2+ primary tumors showed higher P-Rex1 expression than primary triple-negative tumors.

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 differentially expressed in metastatic tumors based on site and receptor status.

The role of P-Rex1 in the development of breast cancer metastases and as a predictive biomarker of therapeutic response warrants further investigation.