This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoos, A. Articles by Ghossein, R. Search for Related Content PubMed PubMed Citation Articles by Hoos, A. Articles by Ghossein, R.

(American Journal of Pathology. 2002;160:175-183.)
© 2002 American Society for Investigative Pathology

Regular Articles

Clinical Significance of Molecular Expression Profiles of Hürthle Cell Tumors of the Thyroid Gland Analyzed via Tissue Microarrays

Axel Hoos^*, Alexander Stojadinovic^*, Bhuvanesh Singh^*, Maria E. Dudas, Denis H. Y. Leung, Ashok R. Shaha^*, Jatin P. Shah^*, Murray F. Brennan^*, Carlos Cordon-Cardo and Ronald Ghossein

From the Departments of Surgery,^*
Pathology,
Biostatistics,
and the Laboratory of Epithelial Cancer Biology,
Memorial Sloan-Kettering Cancer Center, New York, New York

Hürthle cell tumors are rare thyroid neoplasms for which disease biology is poorly understood and diagnosis of carcinoma can be challenging. The aim of the study was to characterize molecular expression profiles of Hürthle cell tumors and to determine the clinical significance of identified phenotypes. Paraffin-embedded tissue cores of normal thyroid (n = 18), and histopathologically well-defined Hürthle cell adenomas (n = 27), Hürthle cell tumors of unknown malignant behavior (n = 7), and minimally (n = 14) and widely (n = 21) invasive Hürthle cell carcinomas were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, and Ki-67 were detected by immunohistochemistry and correlated with clinicopathological data and patient outcome using standard statistical methodology. Median follow-up time was 8 years. High Ki-67 proliferative index was evident only in the clinically aggressive widely invasive Hürthle cell carcinomas and was associated with significantly reduced relapse-free (P = 0.001) and disease-specific (P < 0.001) survival. The molecular phenotype of Hürthle cell tumors, independent of histopathological subtype diagnosis, was characterized by p53(-), mdm-2(+), p21(±), cyclin D1(-), and Bcl-2(±). Normal thyroid tissue demonstrated a p53(-), mdm-2(-), p21(-), cyclin D1(-), and Bcl-2(+) phenotype. The Bcl-2(+) phenotype was associated with improved relapse-free survival (P = 0.04) and disease-specific survival (P = 0.01) in widely invasive carcinomas and the Ki-67(+)/Bcl-2(-) phenotype was associated with the diagnosis of widely invasive Hürthle cell carcinoma (P < 0.001). This study demonstrates that tissue microarray-based profiling allows identification of molecular markers that are associated with patient prognosis. High Ki-67 proliferative index was associated with adverse outcome in Hürthle cell neoplasms. Together with down-regulation of Bcl-2, high Ki-67 proliferative index may be useful for diagnosing widely invasive Hürthle cell carcinomas. Molecular alterations in the p53 pathway play a role in Hürthle cell tumorigenesis, but other unidentified molecular changes seem to be required to induce the malignant phenotype.

This article has been cited by other articles:

				Z. V. Maizlin, S. M. Wiseman, P. Vora, J. M. Kirby, A. C. Mason, D. Filipenko, and J. A. Brown Hurthle Cell Neoplasms of the Thyroid: Sonographic Appearance and Histologic Characteristics J. Ultrasound Med., May 1, 2008; 27(5): 751 - 757. [Abstract] [Full Text] [PDF]

				K. Fujarewicz, M. Jarzab, M. Eszlinger, K. Krohn, R. Paschke, M. Oczko-Wojciechowska, M. Wiench, A. Kukulska, B. Jarzab, and A. Swierniak A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping Endocr. Relat. Cancer, September 1, 2007; 14(3): 809 - 826. [Abstract] [Full Text] [PDF]

				Z. Zheng, G. Bepler, A. Cantor, and E. B. Haura Small Tumor Size and Limited Smoking History Predicts Activated Epidermal Growth Factor Receptor in Early-Stage Non-small Cell Lung Cancer Chest, July 1, 2005; 128(1): 308 - 316. [Abstract] [Full Text] [PDF]

				F. Weber, L. Shen, M. A. Aldred, C. D. Morrison, A. Frilling, M. Saji, F. Schuppert, C. E. Broelsch, M. D. Ringel, and C. Eng Genetic Classification of Benign and Malignant Thyroid Follicular Neoplasia Based on a Three-Gene Combination J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2512 - 2521. [Abstract] [Full Text] [PDF]

				F. Weber, M. A. Aldred, C. D. Morrison, C. Plass, A. Frilling, C. E. Broelsch, K. A. Waite, and C. Eng Silencing of the Maternally Imprinted Tumor Suppressor ARHI Contributes to Follicular Thyroid Carcinogenesis J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1149 - 1155. [Abstract] [Full Text] [PDF]

				S. Chevillard, N. Ugolin, P. Vielh, K. Ory, C. Levalois, D. Elliott, G. L. Clayman, and A. K. El-Naggar Gene Expression Profiling of Differentiated Thyroid Neoplasms: Diagnostic and Clinical Implications Clin. Cancer Res., October 1, 2004; 10(19): 6586 - 6597. [Abstract] [Full Text] [PDF]

				R. Simon, S. Panussis, R. Maurer, H. Spichtin, K. Glatz, C. Tapia, M. Mirlacher, A. Rufle, J. Torhorst, and G. Sauter KIT (CD117)-Positive Breast Cancers Are Infrequent and Lack KIT Gene Mutations Clin. Cancer Res., January 1, 2004; 10(1): 178 - 183. [Abstract] [Full Text] [PDF]

				A. Hoos, A. Nissan, A. Stojadinovic, J. Shia, C. V. Hedvat, D. H. Y. Leung, P. B. Paty, D. Klimstra, C. Cordon-Cardo, and W. D. Wong Tissue Microarray Molecular Profiling of Early, Node-negative Adenocarcinoma of the Rectum: A Comprehensive Analysis Clin. Cancer Res., December 1, 2002; 8(12): 3841 - 3849. [Abstract] [Full Text] [PDF]