Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer.

Esther De Boer,Gooitzen M Van Dam,Marleen Van Oosten,Tineke Van Der Sluis,Lucia M A Crane,Joost Bart,Ate G J Van Der Zee,Bert Van Der Vegt,Philip S Low,Henriette J G Arts,Paulien Kooijman

doi:10.1371/journal.pone.0135012

Esther De Boer, Gooitzen M Van Dam + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0135012

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Abstract

AimsTumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-α) has already been identified as a suitable target for cancer therapy and imaging. FR-α is present on ~40% of human cancers. FR-β is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-β expression in solid tumors. Additional or simultaneous expression of FR-β could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-β is evaluated in ovarian, breast and colorectal cancer.MethodsFR-β expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis.ResultsFR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-β expression in macrophages. FR-β status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-β expression (p=0.022).ConclusionsFR-β expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-β is not regarded as a suitable target in colorectal cancer.

Highlights

The folate receptor (FR) has been proposed as a target in cancer therapy and imaging
FR-β expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples
From the present study we conclude that the low FR-β expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes

Summary

Introduction

The folate receptor (FR) has been proposed as a target in cancer therapy and imaging. Some healthy tissues and a number of pathologic processes express the transmembrane FR which has in the past two decades attracted attention as a target for diagnostic and therapeutic compounds because of its much higher affinity for folate [2]. The FR gene family includes four isoforms: FR-α, FR-β, FR-δ and FR-γ. The latter two play a role in regulatory T-cells and fall outside the scope of this article. The value of FRα targeting in cancer diagnosis and therapy has been shown using folate-conjugated imaging agents as well as folate-based drugs [6,7,8]

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