AQP4 and Histone H1.5 Immunostaining Can Distinguish Benign Oncocytic Follicular Lesions from Oncocytic Follicular Carcinoma.
Julie Chepovetsky, David E Burstein, Eric Genden, Michael Rivera. Mount Sinai Medical Center, NYC, NY
Background: The accurate pre-operative diagnosis of follicular patterned lesions of the thyroid on fine needle aspiration specimens remains elusive. Frequently, it is difficult to distinguish oncocytic follicular neoplasms from cellular hyperplastic oncocytic nodules or foci of nodular oncocytic metaplasia in lymphocytic thyroiditis. Aquaporin 4 (AQP4) is an integral membrane protein that conducts water through the cell membrane. It is expressed in cells of the kidney, CNS and thyroid. Histone H1 (H1.5) is a member of the histone family and functions as a “linker” molecule, playing a role in organizing nucleosomes into higher-order structures. In this study, we evaluate the differences in AQP4 and H1.5 expression in various encapsulated follicular neoplasms and non-neoplastic lesions of the thyroid in surgical pathology specimens.
Design: 85 cases from 2002 to 2009 were selected that were previously diagnosed as Oncocytic follicular adenoma (OA, n=11), Oncocytic follicular carcinoma (OC, n=15), nodular hyperplasia (NH, n=14), and lymphocytic thyroiditis (LT, n=11). All cases were reviewed to confirm the original diagnosis. Immunohistochemical analysis with rabbit produced antibodies to AQP4 (concentration: 0.53 mg/ml, dilution: 1:3000) and Histone H1.5 (concentration 0.5 μg/ml, dilution 1:800) was performed on a representative section from each case. Staining for AQP4 was considered positive if >30% of the cells were highlighted in a membranous pattern. A positive cut-off of >20% of cells showing distinct nuclear staining was set for H1.5.
Results: Normal thyroid is characteristically AQP-positive and H1.5 negative. All cases of NH and 82% (9/11) of LT cases were positive for AQP4. In cases of NH with extensive oncocytic metaplasia staining for AQP4 was particularly intense. H1.5 was negative in all cases of NH and LT. 100% of OA stained positive for AQP4 while only 9% (1/11) were positive for H1.5.. In contrast, 73 % (11/15) of OC were AQP-negative, while 53% (8/15) of HC were positive for H1.5
Conclusions: The combination of AQP4 and H1.5 immunostaining can distinguish many benign oncocytic follicular lesions from oncocytic follicular carcinoma. This combination of markers may play a role in the pre-operative assessment of oncocytic follicular lesions.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 36, Tuesday Afternoon