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. 2017:2017:4537532.
doi: 10.1155/2017/4537532. Epub 2017 Jun 15.

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

Jonathan D Marotti  1   2 , Kristen E Muller  1 , Laura J Tafe  1   2 , Eugene Demidenko  3 , Todd W Miller  2   4
Affiliations

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

Jonathan D Marotti et al. Int J Breast Cancer. 2017.

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.

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Figures

Figure 1
Figure 1
P-Rex1 expression in primary breast tumors. P-Rex1 is highly expressed in luminal (Lum) compared to triple-negative (TN) breast cancers. Each point represents mean P-Rex1 histoscore from two pathologists. Horizontal bars indicate mean histoscore for each receptor subtype. Data were analyzed by ANOVA followed by Tukey's HSD post hoc testing between groups.
Figure 2
Figure 2
P-Rex1 immunohistochemical expression in primary breast cancers and metastatic sites. (a) Primary ER+ tumor with high expression. (b) Primary HER2+ tumor with high expression. (c) Primary triple-negative tumor with no detectable expression in malignant cells. (d) HER2+ lung metastasis with high expression. (e) ER+/HER2− brain metastasis with high expression. (f) ER+/HER2− bone metastasis with no detectable expression in malignant cells. All images were obtained at 200x magnification.
Figure 3
Figure 3
P-Rex1 expression in metastatic breast cancers. P-Rex1 expression is lower in bone metastases compared to brain, lung, and liver metastases. Each point represents mean P-Rex1 histoscore from two pathologists. Horizontal bars indicate mean histoscore for each receptor subtype within each metastatic site.
Figure 4
Figure 4
P-Rex1 expression in matched primary breast tumors and metastases. Each point represents mean P-Rex1 histoscore from two pathologists. Lines indicate matching pairs and metastatic tumors.
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