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

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 pri...

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Main Authors: Jonathan D. Marotti, Kristen E. Muller, Laura J. Tafe, Eugene Demidenko, Todd W. Miller
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:International Journal of Breast Cancer
Online Access:http://dx.doi.org/10.1155/2017/4537532
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author Jonathan D. Marotti
Kristen E. Muller
Laura J. Tafe
Eugene Demidenko
Todd W. Miller
author_facet Jonathan D. Marotti
Kristen E. Muller
Laura J. Tafe
Eugene Demidenko
Todd W. Miller
author_sort Jonathan D. Marotti
collection DOAJ
description 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.
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spelling doaj-art-5257efab128c4d16aff4b241fa1b45e22025-08-20T02:05:42ZengWileyInternational Journal of Breast Cancer2090-31702090-31892017-01-01201710.1155/2017/45375324537532P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic SiteJonathan D. Marotti0Kristen E. Muller1Laura J. Tafe2Eugene Demidenko3Todd W. Miller4Department of Pathology & Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USADepartment of Pathology & Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USADepartment of Pathology & Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USADepartment of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USAComprehensive Breast Program, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USABackground. 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.http://dx.doi.org/10.1155/2017/4537532
spellingShingle Jonathan D. Marotti
Kristen E. Muller
Laura J. Tafe
Eugene Demidenko
Todd W. Miller
P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
International Journal of Breast Cancer
title P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
title_full P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
title_fullStr P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
title_full_unstemmed P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
title_short P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site
title_sort p rex1 expression in invasive breast cancer in relation to receptor status and distant metastatic site
url http://dx.doi.org/10.1155/2017/4537532
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