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

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

Validation anti-human FR-β specificity and immunoreactivity.

<p><i>A</i>: Strong staining was appreciated in the placental villous stroma known to express FR-β, validating anti human FR-β binding specificity and immunoreactivity <i>B</i>: Absent staining was shown after staining with the secondary antibody only. Co-expression of the <i>C</i>: anti-CD68 stain and <i>D</i>: FR-β in activated macrophages in a diverticulitis sample validated anti-human FR-β specificity and immunoreactivity.</p

Characteristics ovarian cancer patients.

<p>Characteristics ovarian cancer patients.</p

FR-β expression in representative samples.

<p><i>A</i>: weak expression (staining intensity 1). <i>B</i>: moderate expression (staining intensity 2). <i>C</i>: strong expression (staining intensity 3).</p

Characteristics breast cancer patients.

<p>Characteristics breast cancer patients.</p