Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;192(1):43-52.
doi: 10.1007/s10549-021-06452-9. Epub 2022 Jan 15.

Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes

Ana Carolina Pavanelli  1   2 , Flavia Rotea Mangone  1   2 , Piriya Yoganathan  3 , Simone Aparecida Bessa  1   2 , Suely Nonogaki  4 , Cynthia A B de Toledo Osório  4 , Victor Piana de Andrade  4 , Iberê Cauduro Soares  5 , Evandro Sobrosa de Mello  5 , Lois M Mulligan  3 , Maria Aparecida Nagai  6   7
Affiliations

Comprehensive immunohistochemical analysis of RET, BCAR1, and BCAR3 expression in patients with Luminal A and B breast cancer subtypes

Ana Carolina Pavanelli et al. Breast Cancer Res Treat. 2022 Feb.

Abstract

Purpose: Breast cancer (BC) is considered a heterogeneous disease composed of distinct subtypes with diverse clinical outcomes. Luminal subtype tumors have the best prognosis, and patients benefit from endocrine therapy. However, resistance to endocrine therapies in BC is an obstacle to successful treatment, and novel biomarkers are needed to understand and overcome this mechanism. The RET, BCAR1, and BCAR3 genes may be associated with BC progression and endocrine resistance.

Methods: Aiming to evaluate the expression profile and prognostic value of RET, BCAR1, and BCAR3, we performed immunohistochemistry on tissue microarrays (TMAs) containing a cohort of 361 Luminal subtype BC.

Results: Low expression levels of these three proteins were predominantly observed. BCAR1 expression was correlated with nuclear grade (p = 0.057), and BCAR3 expression was correlated with lymph node status (p = 0.011) and response to hormonal therapy (p = 0.021). Further, low expression of either BCAR1 or BCAR3 was significantly associated with poor prognosis (p = 0.005; p = 0.042). Pairwise analysis showed that patients with tumors with low BCAR1/low BCAR3 expression had a poorer overall survival (p = 0.013), and the low BCAR3 expression had the worst prognosis with RET high expression stratifying these patients into two different groups. Regarding the response to hormonal therapy, non-responder patients presented lower expression of RET in comparison to the responder group (p = 0.035). Additionally, the low BCAR1 expression patients had poorer outcomes than BCAR1 high (p = 0.015).

Conclusion: Our findings suggest RET, BCAR1, and BCAR3 as potential candidate markers for endocrine therapy resistance in Luminal BC.

Keywords: BCAR1; BCAR3; Breast cancer; Endocrine resistance; RET.

PubMed Disclaimer

References

    1. Beca F, Polyak K (2016) Intratumor heterogeneity in breast cancer. Adv Exp Med Biol 882:169–189. https://doi.org/10.1007/978-3-319-22909-6_7 - DOI - PubMed
    1. Braunstein LZ, Taghian AG (2016) Molecular phenotype, multigene assays, and the locoregional management of breast cancer. Semin Radiat Oncol 26:9–16. https://doi.org/10.1016/j.semradonc.2015.08.002 - DOI - PubMed
    1. Mulligan LM (2014) RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer 14:173–186. https://doi.org/10.1038/nrc3680 - DOI - PubMed
    1. Plaza-Menacho I, Mologni L, McDonald NQ (2014) Mechanisms of RET signaling in cancer: current and future implications for targeted therapy. Cell Signal 26:1743–1752. https://doi.org/10.1016/j.cellsig.2014.03.032 - DOI - PubMed
    1. Boulay A, Breuleux M, Stephan C, Fux C, Brisken C, Fiche M, Wartmann M, Stumm M, Lane HA, Hynes NE (2008) The Ret receptor tyrosine kinase pathway functionally interacts with the ERalpha pathway in breast cancer. Cancer Res 68:3743–3751. https://doi.org/10.1158/0008-5472.CAN-07-5100 - DOI - PubMed

Substances

LinkOut - more resources