Abstract
7585 Background: Estrogen receptor (ERS-1) is the prototype predictive marker in breast cancer (BC). ERS-1 positive BC has a better prognosis, strong tropism to metastasize into the bones and responds to endocrine treatment. The prognostic value of hormone receptor expression in non-small cell lung cancer (NSCLC) until now is less established. Methods: DNA and mRNA were isolated from formalin-fixed, paraffin embedded primary tumor tissue specimen from 78 metastatic NSCLC patients. The cohort was split into finding cohort (n=34) and validation cohort (n=44) by clinical site. Real time RT-PCR has been performed from ESR1, PGR and SNAI2. A Two-Gene-Ratio using the inversely related transcription factors ESR1 and SNAI2 was generated. mRNA expression of the candidate gene was correlated to site of metastatic lesion. In addition, Affymetrix microarray data from 138 non-metastatic NSCLC patients undergoing curative surgery were retrieved from public data bases (Lee et al. Clin Cancer Research 2008). Prognostic value of ESR1, PGR and SNAI2 mRNA expression were analyzed by unsupervised Cluster analysis, partitioning tests and Kaplan Meier estimates of recurrence free survival. Results: Within the FFPE validation cohort the ESR1/SNAI2 ratio was positively associated with bone metastasis (r=0.29) and negatively associated with liver and brain metastasis (r=0.32 and r=0.26, respectively). Additionally, there was a trend toward better survival in the ESR-1 expressing cohorts. Cluster analysis in the non-metastatic microarray cohort identified a hormone receptor positive subtype of superior recurrence free survival. Both hormone receptors, ESR1 and PGR, significantly predicted good outcome in 138 female and male NSCLC patients (log rank p=0.003 and p=0.002, respectively). Conclusions: Resembling BC, hormone receptors are prognostic factors indicating metastatic tropism to the bones and comparably outcome in early stage NSCLC. These results indicate, that NSCLC patients as well may be stratified according to their hormonal status to receive endocrine and bone preserving treatment options. These findings warrant prospectively stratified endocrine trials.
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