title: Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer.
abstract: OBJECTIVE
  Tumor-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.
  
  
  METHODS
  FR-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.
  
  
  RESULTS
  FR-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).
  
  
  CONCLUSIONS
  FR-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.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: de Boer
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Lucia M A
authors.initials: LM
authors.lastname: Crane
authors.affiliation: Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Marleen
authors.initials: M
authors.lastname: van Oosten
authors.affiliation: Department of Pathology and Molecular Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: van der Vegt
authors.affiliation: Department of Pathology and Molecular Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Tineke
authors.initials: T
authors.lastname: van der Sluis
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Paulien
authors.initials: P
authors.lastname: Kooijman
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.affiliation: Department of Gynaecological Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.affiliation: Department of Gynaecological Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henriette J G
authors.initials: HJ
authors.lastname: Arts
authors.affiliation: Department of Surgery, Nuclear Medicine and Molecular Imaging and Intensive Care, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gooitzen M
authors.initials: GM
authors.lastname: van Dam
authors.affiliation: Department of Pathology and Molecular Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Bart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004239:Diverticulitis, Colonic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D058976:Folate Receptor 2 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D061848:Optical Imaging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis
chemical_list: D058976:Folate Receptor 2