The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non-small cell lung cancer

Abstract

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non-small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT-quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non-small cell lung cancer (NSCLC) patients, treated in a first-line registry trial. For validation, 53 patients from a randomized multicentre first-line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p 5 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p 5 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p 5 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.In advanced non-small cell lung cancer (NSCLC), encouraging efforts were achieved in the last years towards individualized and targeted therapies by identification of driver mutations and predictive biomarkers. Meanwhile, EGFR tyrosine kinase inhibitors are standard of care in patients with activating epidermal growth factor receptor (EGFR) mutations, 1,2 leading to significant increase in response rates, quality of life and progression-free survival (PFS) by improvement of side effects. Recently, EML4-ALK translocations were identified in a small subset of patients with adenocarcinoma of the lung, and this lead to approval of crizotinib, a drug targeting this translocation, in a very short period of time.3 Nevertheless, despite this encouraging development in targeted therapies, for the majority of patients yet there are no approved targetable genetic alterations identified. Therefore, it is of utmost importance to identify new targets for individualized therapy in metastatic lung cancer. The estrogen receptor (ER) is a prototype of a predictive biomarker and its expression in breast cancer is an established guide for antihormonal anticancer treatment. In lung cancer, the sex hormone receptor family is far less extensively explored. However, there are clinical data that give hints about an involvement in this entity as well. Fu et al.4 could demonstrate that significantly more pre-menopausa...

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

“…Five of these studies were carried out in Europe and one was conducted in the USA. Four of them took the median levels of ESR1 mRNA expression as cut-off points to differentiate the positive (≥median) and negative (<median) status [12][13][14], the other two studies considered the highest two tertiles as positive and the lowest tertile as negative status [16]. All included ESR1 studies directly reported unadjusted HRs and their 95%CIs, whilst only three of them provided adjusted HRs and their 95% CIs.…”

Gene expression profile for predicting survival of patients with meningioma

“…It is also reported that CD200 could be a new prognostic factor in acute myeloid leukaemia (21). ESR1, a ligand-activated transcription factor, involves in pathological processes of breast (22)(23)(24)(25), prostate (26) and non-small cell lung cancer (27).…”

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

“…On the other hand, there were some new studies on RNA expression of ERs in NSCLC [35,36] . Brueckl et al [35] reported that ER-α high expression was of significant positive prognostic value and patients with ER-α high tumors did not have any benefit from adjuvant chemotherapy.…”

“…Brueckl et al [35] reported that ER-α high expression was of significant positive prognostic value and patients with ER-α high tumors did not have any benefit from adjuvant chemotherapy. Atmaca et al [36] demonstrated that ER-α mRNA expression was an independent prognostic factor in metastatic NSCLC. These studies were interesting because of different approach from immunohistochemistry, however, there were small size and needed to be more studied in the future.…”