Folate Receptor α Expression Level Correlates With Histologic Grade in Lung Adenocarcinoma

Abstract

Context.-Folate receptor a (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 FRAtargeted drugs have been developed and are in phases of clinical testing. Folate receptor a 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.Objective.-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.Design.-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 a membranous staining intensity was given a semiquantitative score from 0 to 3þ 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. Conclusions.-Folate receptor a protein was expressed in the majority of lung adenocarcinomas and a minority of lung squamous cell carcinomas. Folate receptor a 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.

Utility of folate receptor alpha immunohistochemistry in cytology specimens of metastatic breast carcinoma, metastatic serous carcinoma of Müllerian origin, and primary lung adenocarcinoma

“…In another study, Zhang et al set the positive cut‐off for FRA immunopositivity of ≥10% cells showing at least 1+ intensity in cases of TNBC . The authors of the current study used the same positivity criteria for FRA IHC in CB as of Zhang et al Very recently, Driver et al used mAb 26B3 (Biocare Medical, Concord, California) and calculated FRA membranous staining by giving a semiquantitative score from 0 to 3+ for triplicate cores of lung carcinomas with a score of 0 to 1.4 was considered low expression (that is, negative) and >1.4 was considered high expression (positive) by IHC.…”

“…Tumor heterogeneity can also be a limiting factor in assessing FRA IHC in CB. Very recently Driver et al has shown that FRA expression correlated with histologic grade for lung ADC and indicated that poorly differentiated ADC or foci of poor differentiation in a heterogeneous tumor may lack FRA protein expression by IHC. Such tumor heterogeneity can also limit the sensitivity of detecting FRA overexpression by IHC in CB preparation.…”

SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target

“…A total of 141 paratumor lung tissues, 145 NSCLC tissues and 49 lung cancer bone metastatic tissues were collected from patients who underwent surgical resection at Changzheng Hospital of the Second Military Medical University (Shanghai, China) between January 2009 and December 2015. Clinical data of the patients including age, sex, tumor size, the 7th American Joint Committee on Cancer stage ( 18 ), pathology grade ( 19 ) and the expression level of SOSTDC1 are summarized in Table I . None of the patients received neoadjuvant chemotherapy or radiotherapy prior to surgery.…”

Combined use of EpCAM and FRα enables the high-efficiency capture of circulating tumor cells in non-small cell lung cancer

“…Folate receptor alpha (FRα), which is a glycosylated phosphatidylinositol-anchored glycoprotein, is highly expressed in a variety of cancers, including head and neck cancer 24 , breast cancer 25 , and ovarian cancer 26 , as well as NSCLC 27 – 30 . Studies have shown that 72–83% of patients with lung adenocarcinoma overexpress FRα on the cell membrane, but there is limited expression in normal adult tissues 27 , 29 . Furthermore, FRα expression appears to be associated with patients who have never smoked 29 , the EGFR gene mutation 27 , 30 , p53 wild-type 30 , low histologic grade, well-differentiated 29 , 30 , better responses to antifolate chemotherapy 27 and a favorable prognosis 30 .…”