-Folate receptor α (FRA) is a glycosylphosphatidylinositol-anchored high-affinity folate receptor that localizes to the apical surface of epithelia when it is expressed in normal tissue. Unlike normal tissues, FRA may localize to the basolateral side in tumors. These features make FRA an attractive drug target, and several FRA-targeted drugs have been developed and are in phases of clinical testing. Folate receptor α protein expression shows intertumoral variability that may correlate with response to therapy and to clinicopathologic parameters. Using immunohistochemistry, a recent study of breast carcinomas found FRA protein expression was associated with triple-negative status and high histologic grade in breast cancer. Although a prior study of lung adenocarcinomas found the expression level of the gene encoding FRA, FOLR1, was significantly increased in low-histologic-grade tumors compared to high-histologic-grade tumors, the relationship between FRA protein expression and histologic grade has not been reported for lung adenocarcinomas.
-To investigate the relationship between FRA protein expression level and clinicopathologic parameters in lung adenocarcinomas, including histologic grade, by performing immunohistochemistry for FRA on a cohort of non-small cell lung carcinomas.
-High-density tissue microarrays constructed from 188 non-small cell lung carcinomas and used in prior studies were immunostained with FRA-specific antibody clone 26B3. Folate receptor α membranous staining intensity was given a semiquantitative score from 0 to 3+ for triplicate cores of tumor and averaged for each tumor. An average semiquantitative score from 0 to 1.4 was considered low expression, and an average semiquantitative score greater than 1.4 was considered high expression.
-The majority (60 of 78; 77%) of lung adenocarcinomas and a minority (4 of 41; 10%) of lung squamous cell carcinomas were positive for FRA. Folate receptor α expression in lung adenocarcinomas compared with squamous cell carcinomas was statistically different (P < .001, χ(2) test). In lung adenocarcinomas, FRA expression level correlated with histologic grade (P = .005, χ(2) test for trend), but no other clinicopathologic parameter. The majority (23 of 27; 85%) of grade 1 adenocarcinomas had high FRA protein expression, whereas approximately half of grade 2 (10 of 19; 53%) and grade 3 (12 of 25; 48%) adenocarcinomas had high FRA protein expression. Out of adenocarcinomas with lepidic growth pattern, 16 of 20 (80%) showed high FRA protein expression. Out of adenocarcinomas with solid growth pattern, 2 of 6 (33%) showed high FRA protein expression. In lung adenocarcinomas, FRA expression level did not correlate with thyroid transcription factor 1, napsin A, or survival.
-Folate receptor α protein was expressed in the majority of lung adenocarcinomas and a minority of lung squamous cell carcinomas. Folate receptor α protein expression correlated with histologic grade for lung adenocarcinomas, and the greatest difference was observed between grade 1 and grade 3. Our results indicate that poorly differentiated adenocarcinomas or focuses of poor differentiation in a heterogeneous tumor may lack FRA protein expression and be more likely to be resistant to FRA-targeting drugs.
大多数（60/78；77%）肺腺癌和少数（4/41；10%）肺鳞癌表达FRA。肺腺癌和肺鳞癌中叶酸盐受体α的表达具有统计学差异（P < .001, χ(2)检验）。肺腺癌中，FRA表达水平与组织学分级（P = .005, χ(2) 趋向性检验）有关，但与其他临床病理学参数无关。大多数（23/27；85%）1级腺癌高表达FRA蛋白，而大约一半2级（10/19；53%）和3级（12/25；48%）腺癌高表达FRA蛋白。贴壁型腺癌中，16/20(80%)呈FRA蛋白高表达。实性型腺癌中，2/6（33%）呈FRA蛋白高表达。肺腺癌中，FRA表达水平与TTF1、napsin A或 survival无关。