Co-Expression of Estrogen Receptor-α36 and Extra-Nuclear Estrogen Receptor-α66 Is Associated with Advanced Pathological and Clinical Stages in Non-Small Cell Lung Cancer
Jian Huang, Alexander C Mackinnon, Arturo Leuvano, Nagarjun (Arjun) Rao. Medical College of Wisconsin, Milwaukee, WI
Background: Previous evidence has suggested that over-expression of estrogen receptors is strongly associated with tumor proliferation and progression, not only in breast cancer but also in lung cancer, particularly in non-small cell lung cancer (NSCLC). It is also well known that estrogen receptor beta (ERβ) is strongly over-expressed, although nuclear associated ER-alpha (ER-α66) is negative or weakly expressed in most NSCLC. ER-α36, a novel spliced form of ER-α66, is highly expressed in breast cancer. Recent studies, by others and us, have demonstrated that ER-α36 is strongly associated with HER2 and EGFR, and triggers non-genomic signaling pathways in breast cancer. Whether ER-α36 expression is associated with pathological and clinical stage in NSCLC has not been studied.
Design: Expression of ER-α36, Nuclear ER-α, Extra-nuclear ER-α, ER-β, PR, HER2 and EGFR was evaluated by immunohistochemistry (IHC) in 71 NSCLC (adenocarcinoma) patients. The association, between ER-α36 expression and clinicopathological characteristics, clinical stage and other biomarkers, was also evaluated. Statistical significance was measured using Fisher's exact test.
Results: ER-α36, extra-nuclear ER-α, ER-β were expressed in all 71 patients. Strong expression of ER-α36, extra-nuclear ER-α, ER-β (Allred score ≥ 6) was observed in 46 (65%), 42 (59%) and 40(56%) patients, respectively. EGFR was expressed in 44 (62%) patients. Nuclear ER-α, PR and HER2 were negative in all patients. ER-α36 and extra-nuclear ER-α were co-expressed in 40(56%) patients. Interestingly, the patients with co-expression of ER-α36 and extra-nuclear ER-α were strongly associated with both clinical stage III – IV (P<0.001),and pathological stage T3 – T4 (p<0.05); Co-expression of ER-α36 and extra-nuclear ER-α was also strongly associated with EGFR (P<0.001), and negatively associated with ER-β (P<0.05).
Conclusions: We have demonstrated that ER-α36 is highly expressed in NSCLC and is co-expressed with extra-nuclear ER-α. Co-expression of ER-α36 and extra-nuclear ER-α appears to associate with advanced clinical and pathological stages in NSCLC. ER-α36/extra-nuclear ER-α expression also associates with EGFR, and suggesting that ER-α36 may play a critical role in activating non-genomic signaling pathways in lung cancer.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 294, Wednesday Afternoon