Immunohistochemical Panel in the Diagnosis of Thyroid Lesions 225 Clinical Research 225 Address correspondence to Dr. Zubair W. Baloch, Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, 3400 Spruce Street, Philadelphia, PA 19104. E-mail: baloch@ mail.med.upenn.edu Endocrine Pathology, vol. 17, no. 3, 225–234, Fall 2006 © Copyright 2006 by Humana Press Inc. All rights of any nature whatsoever reserved. 1046-3976/1559-0097 (Online)/ 06/17:225–234/$30.00 Diagnostic Value of Differential Expression of CK19, Galectin-3, HBME-1, ERK, RET, and p16 in Benign and Malignant Follicular-Derived Lesions of the Thyroid: An Immunohistochemical Tissue Microarray Analysis J. E. Barroeta, MD, Z. W. Baloch, MD, PHD, P. Lal, MD, T. L. Pasha, BS, P. J. Zhang, MD, PHD, and V. A. LiVolsi, MD Abstract Background: Several immunohistochemical markers have been used to aid in the diag- nosis of follicular-derived lesions of the thyroid (FDLT). In this study we analyze the diag- nostic efficacy of an immunopanel of antibodies to cytokeratin-19 (CK19), galectin-3 (GAL-3), HBME-1, anti-MAP kinase (ERK), ret-oncoprotein (RET), and p16 using a tissue microarray consisting of both benign and malignant FDLT. Design: The study cohort consisted of 90 cases of FDLT (53 benign, 37 malignant) embed- ded in a microarray and immunostained with antibodies to CK19, Gal-3, HMBE-1, ERK, RET, and p16. Staining was scored as positive when >25% of the lesional cells showed positive immunostaining. Results: HMBE-1 was expressed in 70% of malignant and 10% of benign FDLT (p value: <0.0001). CK19 and GAL-3 were positive in 70% and 73% of malignant lesions, respec- tively, and 34% of benign FDLT (p value 0.0005 and 0.0015, respectively). ERK was posi- tive in 4% of the benign and 32% of the malignant cases (p value 0.0002). p16 was expressed in 2% and 46% of the benign and malignant lesions, respectively (p value 0.0001). RET positivity was identified in 15% of the benign lesions and 27% of the malig- nant cases (p value 0.0016). Conclusions: HBME-1, ERK, and p16 were more specific for malignancy, whereas CK19 and GAL-3 stained benign lesions with a higher frequency and were not specific for malignant FDLT. RET-oncoprotein showed poor sensitivity and specificity. Key Words: Thyroid; immunohistochemistry; HBME-1; CK19; galectin-3; ERK; RET; p16; follicular-derived. benign and malignant follicular-derived lesions of the thyroid (FDLT) [1,3]. These diagnostic problems could be attributed to the lack of consensus among experts on the malignant criteria in FDLT such as diag- nosing follicular variant of papillary carci- noma (FVPTC) on the basis of subtle nuclear changes and tumor capsular inva- sion as a sole criterion for malignancy in Introduction The most common lesions of the thy- roid encountered by the pathologist origi- nate from the follicular cells. A majority of these lesions can be divided into benign and malignant categories on the basis of nuclear cytology and/or invasive character- istics [1,2]. However, in some cases it can be difficult to clearly distinguish between