SUN-742 Roles of Progesterone Receptor Isoform B in Non-Small Cell Lung Cancer Tumor Progression

Lung cancer is a leading cause of cancer mortality worldwide. Premenopausal women often has worse survival with advanced stages of the disease compared to postmenopausal women, suggesting an involvement of sex steroids and their receptors in the progression of non-small cell lung cancer (NSCLC). Progesterone receptor (PR) was reported to be involved in an inhibition of NSCLC cell proliferation and correlated with better clinical outcome. In addition, PRB suppressed epidermal growth factor (EGF)-induced NSCLC cell proliferation and activation of ERK1/2, in the absence of progestin. However, clinical and biological significance of PRB in NSCLC patients has remained virtually unknown. Therefore, we performed immunohistochemistry using monoclonal antibody specific to the N-terminus of PRB (250H11 mAb) and 1294mAb which could detect both PRA and PRB in 124 NSCLC cases: 94 adenocarcinoma and 30 squamous cell carcinoma (SCC). Overall survival (OS) was analyzed using the Kaplan-Meier plotter (KM plotter) database, examining the correlation between the status of PRs and survival rate of the patients. 19 cases were immunohistochemically positive for PRB and 23 PRA/B positive NSCLC cases, and all of four cases harboring abundant PRs were also positive for PRB. Therefore, PRB positivity was considered to be significantly correlated with the whole PR (<0.01). Of particular interest, the abundance of PR or PRB was significantly correlated with lower tumor size in total NSCLC (p=0.0395) and SCC (p=0.023), and tended to be correlated with pleural invasion in adenocarcinoma cases (p=0.051). In addition, PRB positive cases tend to have lower tumor size than those positive with PRA/B. The analysis using KM plotter also revealed that PR was a good prognostic factor in total NSCLC patients. Our data demonstrated that not only PR but also PRB could be a good prognostic factor and have an important role on tumor progressing in NSCLC patients. In order to further elucidate the molecular mechanisms of PRB signaling in NSCLC, we are now performing further in vitro studies. Results of our present study could contribute to the development of novel therapeutic strategies targeting PR and/or PRB in NSCLC patients.