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
. 2019 Jan 8;19(1):41.
doi: 10.1186/s12885-018-5262-0.

Expression of RET is associated with Oestrogen receptor expression but lacks prognostic significance in breast cancer

Robert Mechera  1 , Savas D Soysal  2 , Salvatore Piscuoglio  3 , Charlotte K Y Ng  3 , Jasmin Zeindler  1 , Edin Mujagic  1 , Silvio Däster  1 , Philippe Glauser  1 , Henry Hoffmann  1 , Ergin Kilic  4 , Raoul A Droeser  1 , Walter P Weber  1 , Simone Muenst  3
Affiliations
Free PMC article

Expression of RET is associated with Oestrogen receptor expression but lacks prognostic significance in breast cancer

Robert Mechera et al. BMC Cancer. .
Free PMC article

Abstract

Background: The Rearranged during Transfection (RET) protein is overexpressed in a subset of Estrogen Receptor (ER) positive breast cancer, with both signalling pathways functionally interacting. This cross-talk plays a pivotal role in the resistance of breast cancer cells to anti-endocrine therapies, and RET expression is assumed to correlate with poor prognosis based on findings in small patient cohorts. The aim of our study was to investigate the impact of RET expression on patient outcome in human breast cancer.

Methods: We performed an immunohistochemical analysis of RET protein expression on a tissue microarray encompassing 990 breast cancer patients and correlated its expression with clinicopathological parameters and survival data.

Results: Expression of RET was detected in 409 out of 990 cases (41.3%). RET and ER expression significantly correlated (p < 0.0001). The Luminal B HER2-positive subtype showed the highest expression rate (48.9%). In univariate and multivariate survival analyses, RET expression had no impact on overall survival.

Conclusion: We confirmed the co-expression of RET and ER, but we did not find RET expression to be an independent prognostic factor in human breast cancer. Clinical trials with newly developed RET inhibitors are needed to evaluate if RET inhibition has a beneficial impact on patient survival in ER positive breast cancer.

Keywords: Breast cancer; Endocrine resistance; Oestrogen receptor; RET; Tissue microarray.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

Ethical standards and patients’ confidentiality were ensured and in line with regulations of the local institutional review board and data safety laws. The study proposal was submitted to and approved by the ethics committee of northern and central Switzerland (Ethikkomission Nordwest- und Zentralschweiz, (EKNZ), Nr. 2014–397). The EKNZ waived the need for patient consent to participate in this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Five representative photographs of breast cancer tissue punches with immunohistochemical staining of breast cancer cells for RET a: absent staining (0), Magnification 200×; b: weak intensity (1+), Magnification 100×; c: weak intensity (1+), Magnification 200×; d: strong intensity (3+), Magnification 100×; e: strong intensity (3+), Magnification 200×
Fig. 2
Fig. 2
a: Kaplan–Meier survival curve for overall survival depending on the expression of RET (univariate analysis); b–f: Kaplan–Meier survival curves for overall survival depending on the expression of RET for the indicated breast cancer intrinsic subtypes
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Morandi A, Plaza-Menacho I, Isacke CM. RET in breast cancer: functional and therapeutic implications. Trends Mol Med. 2011;17(3):149–157. doi: 10.1016/j.molmed.2010.12.007. - DOI - PubMed
    1. Ichihara M, Murakumo Y, Takahashi M. RET and neuroendocrine tumors. Cancer Lett. 2004;204(2):197–211. doi: 10.1016/S0304-3835(03)00456-7. - DOI - PubMed
    1. Mizuno T, Iwamoto KS, Kyoizumi S, Nagamura H, Shinohara T, Koyama K, Seyama T, Hamatani K. Preferential induction of RET/PTC1 rearrangement by X-ray irradiation. Oncogene. 2000;19(3):438–443. doi: 10.1038/sj.onc.1203343. - DOI - PubMed
    1. Esseghir S, Todd SK, Hunt T, Poulsom R, Plaza-Menacho I, Reis-Filho JS, Isacke CM. A role for glial cell derived neurotrophic factor induced expression by inflammatory cytokines and RET/GFR alpha 1 receptor up-regulation in breast cancer. Cancer Res. 2007;67(24):11732–11741. doi: 10.1158/0008-5472.CAN-07-2343. - DOI - PubMed
    1. Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell. 1990;60(4):557–563. doi: 10.1016/0092-8674(90)90659-3. - DOI - PubMed