Concordance of folate receptor-α expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients

Abstract

Folate receptor alpha (FRα) is known to be upregulated in a variety of cancers, including non-small cell lung cancer (NSCLC) and breast cancer. To ensure reliable implementation of diagnostic- and therapeutic agents, concordance of FRα expression between biopsy, primary tumor and metastases is important. Using immunohistochemistry (Mab 26B3.F2) these concordances were investigated in 60 NSCLC and 40 breast cancer patients. False positivity of FRα expression on breast and lung cancer biopsies was limited to less than 5%. In NSCLC, FRα expression was shown in 21/34 adenocarcinomas and 4/26 squamous cell carcinomas (SCC). Concordance of FRα expression between biopsy and primary tumor was achieved in respectively 83% and 91% of adenocarcinomas and SCCs. Approximately 80% of all local and distant metastases of NSCLC patients showed concordant FRα expression as their corresponding primary tumor. In breast cancer, FRα positivity was shown in 12/40 biopsies, 20/40 lumpectomies and 6/20 LN metastases, with concordance of 68% between biopsy and primary tumor and 60% between primary tumor and LN metastases. In conclusion, this study shows high concordance rates of FRα expression between biopsies and metastases compared to primary NSCLC and breast cancers, underscoring the applicability of FRα-targeted agents in these patients.

Targeting folate receptor alpha for cancer treatment

“…A number of studies have reported overexpression of FRα in breast cancers [12, 49]. Most recently, high FRα tissue expression was observed in 74% of estrogen receptor (ER)/progesterone receptor (PR)-negative breast cancers [13, 50–52].…”

“…FRα has been reported to be overexpressed in solid tumors such as ovarian, lung and breast carcinomas [10–12]. On the other hand, the distribution of FRα in normal human tissues is restricted to low level expression in the apical surfaces of some organs such as the kidney, lung and choroid plexus [9].…”

Making cold malignant pleural effusions hot: driving novel immunotherapies

“…261 CAR-T cells targeting fluorescein isothiocyanate (FITC), were generated in conjunction with an intermediate antigen switch composed of folate bound to FITC, thereby binding the folate receptor α (FRα) chain, a cell surface protein that is expressed in over 70% of lung adenocarcinomas. 262,263 This established a pseudoimmunological synapse with FITC-CAR T cells and cells expressing either FRα or FRβ, which is also highly expressed on TAMs in the tumor microenvironment. 261 Potent antigen-specific and dose-dependent in vitro efficacy was demonstrated against NSCLC and macrophage cell lines.…”

Identification of a Folate Receptor-Targeted Near-Infrared Molecular Contrast Agent to Localize Pulmonary Adenocarcinomas

“…We were particularly interested in pursuing patients with pulmonary adenocarcinoma; however, we noted that previous data describing FRa expression in pulmonary adenocarcinomas were ascertained from nonsurgical cohorts. 15,18 Thus, before pursuing IMI with OTL38 in a clinical trial, we evaluated FRa expression within a purely surgical cohort. To this end, histologic samples from 100 pulmonary adenocarcinoma patients who underwent pulmonary resection were immunostained using the anti-FRa mAb 26B3.F2 and scored by a pulmonary pathologist to determine FRa expression.…”