Folate Receptor Expression in Human Parathyroids: A Novel Finding with Imaging and Therapeutic Implications
Susan Muller, Raghuveer K Halkar, Francois K Villinger, Karen Im, Susan A Safley, Jyotirmay Sharma, Collin J Weber. Emory University, Atlanta, GA
Background: Parathyroid (PT) proliferative diseases have increased 300% in the past 2 decades, affecting more than 30,000 new patients annually in the USA. Preoperative localization of PT is suboptimal in as many as 30% of cases detected by 99m Tc-MIBI, resulting in recurrent or persistent disease. 99m Tc-MIBI concentrates in both thyroid and PT tissue, tissues which are frequently in close association. There is a need for a tracer/imaging tool that concentrates in PT more than in the thyroid. In addition PT carcinoma (CA), albeit rare, has no effective medical treatment.
The folate receptor (FR) is highly expressed on a variety of human cancers and holds promise as a therapeutic and imaging target. The aim of this study is to determine whether normal human PT and PT tumors express FR.
Design: 57 PTs were evaluated for FR expression by IHC: (21 adenomas, 9 10 hyperplasias, 13 20 hyperplasias, 5 CA, and 9 normal PTs; IRB approval #26334). Normal adjacent thyroid, thyroid nodules (4) and thyroid medullary CA (2) were also evaluated for FR. FR expression in tissue specimens was analyzed using a goat anti-human FR polyclonal antibody (sc-16387, 1:100 dilution; Santa Cruz Biotechnology, Santa Cruz, CA). Known head and neck squamous cell carcinomas positive for FR were used as the positive control. FR expression was considered positive when either cytoplasmic or membranous staining was present.
FR expression in normal PT (1), PT adenomas (6), PT hyperplasias (5), PT CA (1), and normal thyroid (1) was determined by Western blotting according to standard techniques using a polyclonal goat anti-human FR polyclonal antibody.
Results: Normal PT and all PT proliferative disorders showed strong immunoreactivity for cytoplasmic FR. None of the thyroid tissues were positive for FR with the exception of 1 thyroid medullary CA (<10% FR expression).
By Western blotting, a 50 kDa band (FR) was detected in all PT tissue with the exception of 1 PT adenoma and 1 PT CA. No FR expression was detected in thyroid tissue.
Conclusions: This is the first report of FR expression on human PT cells. These findings may hold potential for future investigations including the use of 99m Tc-folate for identification and localization of PT tumors pre-operatively. Additionally, FR expression in PT neoplasms may have therapeutic applications as folate conjugation to anti-cancer drugs may have the potential to be used to deliver therapeutic agents selectively to PT CA.
Monday, March 19, 2012 1:00 PM
Platform Session: Section H, Monday Afternoon