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

2016 ◽  
Vol 44 (5) ◽  
pp. 369-376 ◽  
Author(s):  
Umer N. Sheikh ◽  
Cynthia Cohen ◽  
Momin T. Siddiqui
Keyword(s):  
Breast Carcinoma ◽  
Lung Adenocarcinoma ◽  
Folate Receptor ◽  
Metastatic Breast ◽  
Serous Carcinoma ◽  
Folate Receptor Alpha ◽  
Metastatic Breast Carcinoma ◽  
Receptor Alpha ◽  
Primary Lung Adenocarcinoma

Folate Receptor Alpha Immunohistochemistry in Cytology Specimens of Metastatic Breast Carcinoma

2015 ◽  
Vol 59 (4) ◽  
pp. 298-304 ◽  
Author(s):  
Umer N. Sheikh ◽  
Cynthia Cohen ◽  
Momin T. Siddiqui
Keyword(s):  
Breast Carcinoma ◽  
Clinical Significance ◽  
Ductal Carcinoma ◽  
Folate Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Folate Receptor Alpha ◽  
Metastatic Breast Carcinoma ◽  
Receptor Alpha

Background: Folate receptor alpha (FRA) is involved in folate accumulation and utilization, and is expressed in varying proportions in breast, ovary and parotid epithelial cells, among others. FRA overexpression by immunohistochemistry (IHC) has been shown in estrogen/progesterone receptor (ER/PR)-negative carcinoma (40-74%) and in triple-negative breast carcinoma (TNBC; 50-86%) in histological specimens of primary breast cancers. We assessed the feasibility of IHC in detecting FRA expression and its patterns and clinical significance in metastatic TNBC in fine-needle aspiration (FNA) cell blocks (CBs). Materials and Methods: Metastatic breast ductal carcinoma cases were retrospectively immunostained with FRA IHC on FNA CBs. FRA staining was scored qualitatively (+/-), by intensity (0-3) and by staining area (0-100%). Of these metastatic cases, a subset of primary breast carcinoma cases was also immunostained with FRA. The results were correlated with ER, PR and human epidermal growth factor receptor 2 (Her2/Neu) performed by routine IHC. Results: A total of 40 FNA CBs with metastatic disease were studied, including hormone (ER/PR) positive (n = 5), triple positive (n = 5), Her2/Neu-only positive (n = 5) and TNBC (n = 25). FRA IHC showed immunoreactivity with moderate positivity in only 1 (4%) TNBC. All the remaining 39 cases were negative for FRA expression. Five cases of primary TNBC were stained with FRA IHC and were negative for FRA expression. Conclusions: Our data suggest that FRA expression by IHC was rarely associated with ER/PR-negative tumors relative to ER/PR-positive tumors and, more importantly, with TNBC in FNA CBs. This finding may have a clinical significance and prognostic implications in metastatic breast carcinoma. Furthermore, 5 primary TNBC cases did not overexpress FRA by IHC. Hence, antifolate receptor therapies do not appear to be clinically relevant in TNBC based on immunostaining of FNA CBs of metastatic breast cancers.

scholarly journals Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuqing Wang ◽  
Jie Huang ◽  
Qiong Wu ◽  
Jingjing Zhang ◽  
Zhiyuan Ma ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Folate Receptor ◽  
Critical Role ◽  
Subsequent Treatment ◽  
Folate Receptor Alpha ◽  
Fractionated Radiotherapy ◽  
Receptor Alpha ◽  
Regulatory Approach ◽  
Promising Treatment

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both in vitro and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.

Antibody-independent ApoStream technology isolates folate receptor alpha (FRA)–positive circulating tumor cells from blood of non-small cell lung adenocarcinoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21028-e21028
Author(s):  
Darren W. Davis ◽  
Christopher Neal ◽  
Vishal Gupta ◽  
Vladislava O. Melnikova ◽  
Jacky Woo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Folate Receptor ◽  
Small Cell ◽  
Normal Donor ◽  
Small Cell Lung ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Nsclc Patients

e21028 Background: The ability to enrich and interrogate circulating tumor cells (CTCs) from blood may allow for the analysis of metastatic dissemination and potential use of CTCs as surrogates for monitoring drug efficacy. We developed ApoStream, a dieletrophoresis field-flow fractionation based platform, for antibody-independent CTC isolation. We demonstrated that ApoStream successfully isolates non-small cell lung adenocarcinoma (NSCLC) CTCs that express Folate Receptor alpha (FRA), a GPI-anchored receptor, which has emerged as a cancer biomarker and potential therapeutic target in multiple cancer types. Methods: ApoStream technology was used to enrich CTCs from NSCLC patients’ blood. CTC enrichment by ApoStream was compared to that of the FDA cleared CellSearch CTC kit. A multiplexed immunofluorescent assay was developed to enable CTC enumeration (Cytokeratin+/CD45-/DAPI+ cells) and analysis of FRA expression (detection by murine antibody clone 26B3) using single cell quantitative laser scanning cytometry (LSC). Results: In a side-by-side comparison with the CellSearch CTC kit, ApoStream isolated significantly higher numbers of CTCs in 9 metastatic adenocarcinoma NSCLC patients (Apostream: mean =139, range 3-487 per 7.5 mL of blood, versus CellSearch kit: mean =2, range 0-8 per 7.5 mL of blood, n= 9, p=0.041). All patients were found to be CTC-positive by ApoStream, while only 3 of 9 (33%) patients were CTC-positive based on the CellSearch kit. LSC analysis demonstrated that 8-33% of all CTCs isolated expressed FRA and that FRA expression was confined to CTCs only. No false positive CTCs and no FRA-expressing cells were isolated by ApoStream from normal donor blood (n=15). Conclusions: All NSCLC adenocarcinoma patients analyzed had FRA-positive CTCs, suggesting that FRA may play a key role in metastasis and that screening of patients with the ApoStream CTC isolation system may identify patients who could benefit from FRA-targeted therapy.

scholarly journals Correlation between folate receptor alpha (FRα) expression and clinicopathological features in lung adenocarcinoma

2019 ◽  
Vol 30 ◽  
pp. ii2
Author(s):  
N. Tamura ◽  
Y. Fujiwara ◽  
T. Hashimoto ◽  
H. Shiraishi ◽  
S. Kitano ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Folate Receptor ◽  
Clinicopathological Features ◽  
Folate Receptor Alpha ◽  
Receptor Alpha

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

Lung Cancer ◽  
2020 ◽  
Vol 145 ◽  
pp. 152-157 ◽  
Author(s):  
Nobumasa Tamura ◽  
Yutaka Fujiwara ◽  
Taiki Hashimoto ◽  
Hideaki Shiraishi ◽  
Shigehisa Kitano ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Folate Receptor ◽  
Clinicopathological Features ◽  
Folate Receptor Alpha ◽  
Receptor Alpha

scholarly journals Significance of Folate Receptor Alpha in Invasive Breast Carcinoma

2014 ◽  
Vol 142 (suppl_1) ◽  
pp. A253-A253
Author(s):  
Jacqueline Nunez ◽  
Mark Bunker ◽  
Jan Silverman ◽  
Uma Krishnamurti
Keyword(s):  
Breast Carcinoma ◽  
Folate Receptor ◽  
Invasive Breast Carcinoma ◽  
Folate Receptor Alpha ◽  
Receptor Alpha
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