Correlation between folate receptor alpha (FRα) expression and clinicopathological features in lung adenocarcinoma
Authors: N. Tamura, Y. Fujiwara, T. Hashimoto, H. Shiraishi, S. Kitano, T. Shimizu, N. Yamamoto, N. Motoi
Journal: Annals of Oncology (2019)

Background: FRα is present on the cell surface, mediates its intracellular transport via receptor-mediated endocytosis, and is also involved in cell division. FRα is expressed at high levels on various cancer cells, and it is considered that FRα could be a potential therapeutic target in FRα-expressing cancers. Methods: We investigated the correlations between FRα expression in tissue microarray (TMA) constructed from surgical specimens of lung adenocarcinoma (LADC) and clinicopathological features including EGFR mutation retrospectively. Two TMA cores per a resected LADC specimen were created using TMA Master (3DHISTECH, Budapest, Hungary) at National Cancer Center Hospital between January 2007 and November 2016. Based on previous studies, if the percentage of stained tumor cells was greater than or equal 5%, FRα was considered as positive, and if H-score was more than or equal 60 (range, 0-300), FRα was considered as high expression. Results: Overall, 466 TMA cores created from 233 patients who underwent surgery for LADC were evaluated; FRα positive expression (FRα-pos)/negative (FRα-neg), 222/11; FRα high expression (FRα-HE)/low (FRα-LE), 190/43, respectively. 124 patients (53.2%) were with EGFR mutation. The median H-scores of FRα expression, rates of FRα-pos, and rates of FRα-HE for EGFR mutation and wild type were 159/104 (p = 0.0002), 97.6/92.7% (p = 0.077), and 88.7/73.4% (p = 0.0026). The median disease free survival (months) were 18.7/23.3 (p = 0.30) for FRα-pos/neg and 20.2/12.8 (p = 0.42) for FRα-HE/LE, respectively. The median overall survival were 92.9/not reached (p = 0.42) for FRα-pos/neg and 92.9/96.4 (p = 0.42) for FRα-HE/LE, respectively. FRα expression was not considered as a prognostic factor in LADC. 82 patients with EGFR mutation received EGFR-TKI after recurrence (FRα-pos/neg, 79/3; FRα-HE/LE, 71/11). Overall response rates and median progression free survival (months) of EGFR-TKI were 59.2/66.6% (p = 0.80) and 16.1/11.5 (p = 0.016) for FRα-pos/neg; 61.8/45.5% (p = 0.31) and 16.2/13.2 (p = 0.95) for FRα-HE/LE, respectively. Conclusions: FRα expression was significantly higher in LADC with EGFR mutation than that with wild-type. The efficacy of EGFR-TKI was better in FRα-pos than in FRα-neg. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: Y. Fujiwara: Research funding: AbbVie, AstraZeneca, BMS, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Incyte, Merck Serono, MSD, Novartis; Advisory role: AstraZeneca, BMS, MSD, Novartis, ONO; Speakers bureau: AstraZeneca, BMS, MSD, Novartis, ONO, Sysmex, Taiho. S. Kitano: Personal fee, grant: Eisai; Honoraria: ONO, Bristol-Myers Squibb, AstraZeneca, Chugai, Pfizer, Sanofi, Nippon Kayaku, Boehringer Ingelheim, Meiji, Taiho, Novartis, Daiichi Sankyo, MSD, Kirin, Celgene, Sumitomo Dainippon; Grant: Regeneron, Astellas, Gilead, AMED, JSPS. T. Shimizu: Advisory board: Takeda, The Consortium on Harmonization of Institutional Requirements for Clinical Research; Corporate sponsored research: Bristol-Myers Squibb, Daiichi Sankyo, Lilly, Novartis, Eisai, Takeda, PharmaMar, FivePrime, 3D-Medicine, Symbio, Chordia. N. Yamamoto: Grants: Quintiles, Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kirin, Takeda, ONO, Janssen, Lilly, MSD, Merck; Advisory: Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cimic; Speakers: BMS, Pfizer, AstraZeneca, Lilly, ONO, Chugai. N. Motoi: Personal fee (lecture, Advisory board): Bristol-Myers Squibb, Miraca Life Sciences, AstraZeneca, Chugai Pharma, MSD, Agilent, Novartis, Roche Diagnostics; Institutional research funding: Roche Diagnostics. All other authors have declared no conflicts of interest.