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

Esther de Boer; Lucia M. A. Crane; Marleen van Oosten; Bert van der Vegt; Tineke van der Sluis; Paulien Kooijman; Philip S. Low; Ate G. J. van der Zee; Henriette J. G. Arts; Gooitzen M. van Dam; Joost Bart

doi:10.1371/journal.pone.0135012

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

Esther de Boer, Lucia M. A. Crane, Marleen van Oosten, Bert van der Vegt, Tineke van der Sluis, Paulien Kooijman, Philip S. Low, Ate G. J. van der Zee, Henriette J. G. Arts, Gooitzen M. van Dam^*, Joost Bart

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Aims

Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer.

Methods

FR-beta 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.

Results

FR-beta 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-beta expression in macrophages. FR-beta 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-beta expression (p=0.022).

Conclusions

FR-beta 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-beta 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-beta is not regarded as a suitable target in colorectal cancer.

Original language	English
Article number	e0135012
Number of pages	13
Journal	PLoS ONE
Volume	10
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0135012
Publication status	Published - 6-Aug-2015

Keywords

EXPRESSION
INFLAMMATION
CLONING
ALPHA
CDNA

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@article{3ed05a40ab354925b52a508262d64bd4,

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

abstract = "AimsTumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer.MethodsFR-beta 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-beta 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-beta expression in macrophages. FR-beta 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-beta expression (p=0.022).ConclusionsFR-beta 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-beta 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-beta is not regarded as a suitable target in colorectal cancer.",

keywords = "EXPRESSION, INFLAMMATION, CLONING, ALPHA, CDNA",

author = "{de Boer}, Esther and Crane, {Lucia M. A.} and {van Oosten}, Marleen and {van der Vegt}, Bert and {van der Sluis}, Tineke and Paulien Kooijman and Low, {Philip S.} and {van der Zee}, {Ate G. J.} and Arts, {Henriette J. G.} and {van Dam}, {Gooitzen M.} and Joost Bart",

year = "2015",

month = aug,

day = "6",

doi = "10.1371/journal.pone.0135012",

language = "English",

volume = "10",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "8",

}

TY - JOUR

T1 - Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer

AU - de Boer, Esther

AU - Crane, Lucia M. A.

AU - van Oosten, Marleen

AU - van der Vegt, Bert

AU - van der Sluis, Tineke

AU - Kooijman, Paulien

AU - Low, Philip S.

AU - van der Zee, Ate G. J.

AU - Arts, Henriette J. G.

AU - van Dam, Gooitzen M.

AU - Bart, Joost

PY - 2015/8/6

Y1 - 2015/8/6

N2 - AimsTumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer.MethodsFR-beta 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-beta 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-beta expression in macrophages. FR-beta 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-beta expression (p=0.022).ConclusionsFR-beta 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-beta 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-beta is not regarded as a suitable target in colorectal cancer.

AB - AimsTumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer.MethodsFR-beta 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-beta 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-beta expression in macrophages. FR-beta 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-beta expression (p=0.022).ConclusionsFR-beta 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-beta 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-beta is not regarded as a suitable target in colorectal cancer.

KW - EXPRESSION

KW - INFLAMMATION

KW - CLONING

KW - ALPHA

KW - CDNA

U2 - 10.1371/journal.pone.0135012

DO - 10.1371/journal.pone.0135012

M3 - Article

C2 - 26248049

SN - 1932-6203

VL - 10

JO - PLoS ONE

JF - PLoS ONE

IS - 8

M1 - e0135012

ER -

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

Abstract

Keywords

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