Correlation between the expression of folate receptor alpha (FRα) and clinicopathological features in patients with lung adenocarcinoma

Objectives: Folate receptor alpha (FR alpha) is expressed on the cell surface, mediates its intracellular transport via receptor-mediated endocytosis, and is involved in cell division. Whether FR alpha could be a potential therapeutic target in FR alpha-expressing cancers remains unknown. Here, we retrospectively investigated the correlations between tumor FR alpha expression in lung adenocarcinoma (LADC) and clinicopathological features. Materials and methods: FR alpha expression was evaluated using a tissue microarray (TMA) constructed from surgical specimens of LADC and compared with clinicopathological features including the EGFR mutation status and the expressions of PD-L1, PD-L2, PD-1, CD4, CD8, CD204, and alpha SMA. If the proportion of positively stained tumor cells was greater than or equal to 5%, the tumor was considered to show FR alpha expression; if the H-score was more than or equal to 60, the tumor was considered to show high FR alpha expression. Results: Overall, 466 TMA cores created from 233 LADC patients were evaluated: FR alpha-positive expression (FR alpha-pos)/negative (FR alpha-neg), 222/11; FR alpha high expression (FR alpha-HE)/low (FR alpha-LE), 190/43. An EGFR mutation was present in 53.2 % of the patients. The median H-score of FR alpha expression, FR alpha-pos rate, and FR alpha-HE rate for EGFR mutation/wild type were 159/104 (p= 0.0002), 97.6/92.7 % (p= 0.0773), and 88.7/73.4 % (p= 0.0026), respectively. The H-scores for FR alpha had mild correlations with the proportion of tumor cells with positive staining for PD-L1 (r=-0.2557, p < 0.0001), the number of CD8-positive cells per square millimeter (r=-0.1767, p= 0.0069), and the area with positive staining for alpha SMA (r= 0.2049, p= 0.0017). No correlations were seen between FRa expression and other cancer-immunity markers. Conclusion: Tumor FR alpha expression was significantly higher in LADCs with EGFR mutation than in those with wild-type EGFR. This study suggested that FR alpha expression was related to cancer and microenvironment-immunity markers such as PD-L1 expression, CD8 cells, and aSMA.