Abstract
BackgroundThe 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.MethodsWe 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.ResultsExpression 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.ConclusionWe 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.
Highlights
The Rearranged during Transfection (RET) protein is overexpressed in a subset of Estrogen Receptor (ER) positive breast cancer, with both signalling pathways functionally interacting
The relatively high proportion of luminal B subtype cancers in our population could be partly due to the low threshold of Ki-67at ≥14% and the fact that Ki-67 was evaluated on the tissue microarrays (TMA) tissue punches, which does not account for heterogeneity of Ki-67 distribution and might have led to an overestimation of Ki-67 expressing cells in some cancers
Together with the fact that the Luminal B subtype is characterised by poorer prognosis within ER positive breast cancers [33], these results suggest a correlation of an activated glial cell line-derived neurotrophic factor (GDNF) signalling cascade resulting in RET activation
Summary
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 Rearranged during Transfection (RET) protein belongs to the receptor tyrosine kinase (RTK) superfamily encoded by the RET gene on the human chromosome 10q11.2 [1].
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