Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

Abstract

Although a wide range of studies have addressed the relationship between estrogen receptor (ER) expression and prognosis in non-small cell lung cancer (NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Estrogen receptor; Non-small cell lung cancer; Epidermal growth factor receptor; Fulvestrant; Combined therapy Core tip: Although there were many studies regarding the role of estrogen receptor (ER) in non-small cell lung cancer (NSCLC), the rate of ER expression or the intracellular distribution of ER remains controversial. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. Furthermore, there has been little functional analysis for ER variants. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.Kawai H. Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer.

Prognostic value of estrogen receptors mRNA expression in non-small cell lung cancer: A systematic review and meta-analysis

“…ESR protein expression is routinely analyzed by immunohistochemistry (IHC) method. There were a number of studies employed the IHC method to explore the prognostic role of ESR in lung cancer survival and these studies were categorized by location of expression (nuclear or cytoplasm); however, according to a recent qualitative systematic review on the IHC method, contradictive results obtained from insufficient number of studies made it hard to evaluate the virtual prognostic roles of either ESR1 cytoplasm or nuclear expression in NSCLC survival [4]. The scenario of ESR2 cytoplasm expression encountered the same dilemma.…”

“…Estrogen receptor (ESR), with two subtypes -ESR1 and ESR2, is a vital prognostic biomarker of breast cancer [4]. Recent studies showed that both ESR1 and ESR2 were expressed in the majority of human NSCLC cell lines, which provided credible evidence on possible links between sex hormones and NSCLC prognosis [5].…”

Estrogen and cancers of the colorectum, breast, and lung in postmenopausal women

“…As for ER‐β, immunohistocheical positivity has been frequently observed both for the nucleus and cytoplasm in lung cancer. ER‐β nuclear positivity has been related with favorable clinical outcome in most studies, whereas the opposite is true for cytoplasmic positivity . Compared with ER‐β, ER‐α shows great variability in its expression frequency.…”

“…Compared with ER‐β, ER‐α shows great variability in its expression frequency. ER‐α positivity is more usually observed in the cytoplasm than the nucleus in lung cancer, and ER‐α cytoplasmic positivity has been related with poor clinical outcome in NSCLC . Classically, the estrogen‐ER complex localized to the nucleus has been believed to transduce genomic signals; however, the role of cytoplasmic ERs has recently been noted, and the latter is considered important in lung cancer etiology.…”

“…ER-β nuclear positivity has been related with favorable clinical outcome in most studies, whereas the opposite is true for cytoplasmic positivity. 50 Compared with ER-β, ER-α shows great variability in its expression frequency. ER-α positivity is more usually observed in the cytoplasm than the nucleus in lung cancer, and ER-α cytoplasmic positivity has been related with poor clinical outcome in NSCLC.…”