by TheP-value of 0.04 for DDIT3 was found examining a small number of follicular carcinoma (n=8) and follicular adenoma (n=21) tissue microarray specimens. to the tumors and 11 individual cases of normal thyroid parenchyma. All in-house cases of follicular adenomas, follicular carcinomas and adjacent normal thyroid tissue showed positive immunostaining with anti-DDIT3 and anti-STT3A. Anti-ARG2 and anti-FAM129A polyclonal antibodies showed positive staining in 20 and 60% of in-house follicular adenomas, and 40 and 87% of in-house FK866 follicular carcinomas, respectively. Monoclonal anti-FAM129A exhibited positive staining in 13 and 33% of in-house follicular adenomas and follicular carcinomas, respectively. Polyclonal anti-DDIT3, -STT3A and -FAM129A antibodies showed positive staining in all tissue microarray slides of follicular carcinoma and in 76, 85 and 81% of the follicular adenomas, respectively. Monoclonal anti-STT3A stained 81% of the follicular adenoma cores. Anti-ARG2 stained positive in 13% FK866 of follicular carcinomas and 10% of follicular adenomas around the tissue microarray slides. In conclusion, DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma. Keywords:ARG2, C1orf24, DDIT3, FAM129A, ITM1, STT3A, thyroid carcinoma Fine-needle aspiration biopsy has become the most widely used preoperative method to diagnose thyroid nodules.1,2,3Since it’s introduction in Europe in the 1970s, and in the US some years later, there has been a dramatic reduction in the need for diagnostic hemi-thyroidectomies, whereas the yield of thyroid carcinomas has increased.4For papillary carcinomas, cytology smears usually are sufficient to make a diagnosis, due to the presence of cells FK866 with nuclei characteristic for papillary carcinoma. In marked contrast, in follicular neoplasias, cytological morphology cannot reliably distinguish between benign follicular adenomas and malignant follicular carcinomas.5,6,7,8,9,10Indeed, a definite diagnosis of follicular carcinoma requires surgical excision for histological characterization and the examination of multiple paraffin sections for evidence of capsular or vascular invasion. The reported rate of malignancy in follicular-patterned TSHR lesions diagnosed as either atypical or indeterminate ranges between 20 and 30%,5,8,11,12,13,14,15,16,17,18,19,20,21,22and many patients are operated upon unnecessarily. The cost of these procedures is usually high, both economically and in patient morbidity. Recently, a number of promising molecular and immunohistochemical methods have been described, which could improve FK866 the diagnostic accuracy of fine-needle aspiration biopsy.23,24,25,26,27,28,29However, there is some inter-laboratory variability in the sensitivity and specificities obtained with the individual techniques as shown in the review by Griffithet al.30Significantly, none of the methods has been fully validated to the extent that it is in general use in the routine diagnostic laboratory. In 2006, Ceruttiet al31described a test that could discriminate between follicular carcinoma and follicular adenoma on both paraffin sections and cytology preparations. Their original immunohistochemical method was based on the selective staining of follicular carcinoma cells by antibodies reactive to four protein markers: DDIT3 (also known as CHOP and GADD153), STT3A (also known as ITM1), ARG2 and FAM129A (also known as C1orf24 and Niban). Overexpression of these proteins was first observed using serial analysis of gene expression procedures on a single follicular carcinoma specimen and subsequently confirmed using quantitative reverse-transcription PCR. The four proteins have diverse cellular functions including nitric oxide and polyamine metabolism (ARG2), regulation of protein translation (FAM129A), regulation of transcription as CCAAT/enhancer-binding transcription factor (DDIT3), and as component of the N-oligosaccharide transfer enzyme (STT3A). Ceruttiet al31,32found, by using immunohistochemistry, that this combination of the four markers distinguished a variety of thyroid tumors commonly classified as indeterminate on fine-needle aspiration biopsy, with an estimated sensitivity of 100% and specificity of 85% for detecting malignancy. The aim of this study was to verify the predictive accuracy of the new biomarkers DDIT3, STT3A, ARG2 and FAM129A in distinguishing follicular carcinoma from follicular adenoma. == Materials and methods == == Tissue Sections == Formalin-fixed, paraffin-embedded thyroid tissue blocks were retrieved from the archive maintained at the Department of Pathology, The Norwegian Radium Hospital. A total of 30 cases, consisting of 15 follicular carcinomas and 15 follicular adenomas, originally submitted for diagnostic purposes, were included. The in-house cases have been diagnosed histopathologically according to World Health Organization criteria.33Follicular neoplasias with oncocytic differentiation, FK866 and areas containing cells demonstrating oncocytic differentiation, were excluded from the evaluation. In all cases, hematoxylin and eosin-stained slides.
