Abstract
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.
Highlights
It is well-established that breast cancer is a heterogenous disease comprised of several subgroups
P-Rex1 expression was evaluated in 133 cases by IHC from 101 patients: 42 primary breast tumors from patients who did not develop distant metastasis within 3–11 years of follow-up; 40 primary breast tumors from patients who later developed distant metastasis; and 51 breast-derived metastatic tumors, of which 36 had a matching primary breast tumor available for analysis
There was a significant difference in P-Rex1 expression in primary breast cancers based on receptor status (ANOVA p = 0.019)
Summary
It is well-established that breast cancer is a heterogenous disease comprised of several subgroups. Luminal A (ER+ and/or PR+ but HER2−) breast cancers tend to develop bone metastasis with better survival compared to the visceral metastases associated with triple-negative breast cancers (TNBCs, which are ER−, PR−, and HER2−) [4]. In light of these inherent differences in metastatic patterns, a better understanding of the biology, within molecular signaling pathways, may lead to novel therapeutic approaches and enhanced prediction of patient outcomes. The role of P-Rex in the development of breast cancer metastases and as a predictive biomarker of therapeutic response warrants further investigation
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