North Pacific Surgical Association Immunophenotyping of thyroid tumors identifies molecular markers altered during transformation of differentiated into anaplastic carcinoma Sam M. Wiseman, M.D., F.R.C.S.C. a, *, Obi L. Griffith, Ph.D. b , Allen Gown, M.D. c,d , Blair Walker, M.D. c,e , Steven J. M. Jones, Ph.D. b a Department of Surgery, St Paul’s Hospital/University of British Columbia, Vancouver, BC, Canada; b Department of Medical Genetics, University of British Columbia, British Columbia Cancer Agency, and Michael Smith Genome Sciences Center, Vancouver, BC, Canada; c Department of Pathology, University of British Columbia, Vancouver, BC, Canada; d PhenoPath Laboratories, Seattle, WA, USA; and e Department of Pathology and Laboratory Medicine, St Paul’s Hospital, Vancouver, BC, Canada Abstract BACKGROUND: The objective of this study was to evaluate the change in the tumor expression profile that occurs during the transformation of differentiated thyroid cancer (DTC) into anaplastic thyroid cancer (ATC) and to evaluate an 8-marker transformation panel previously identified through evaluation of ATCs and their adjacent associated DTCs. METHODS: Tissue microarrays were constructed from 19 ATCs and 96 DTCs (90 papillary carci- nomas and 6 follicular carcinomas), and immunohistochemistry was used to evaluate the expression of 54 molecular markers. Significant associations between marker staining and cancer pathology (DTC vs ATC) were determined using contingency table and marginal homogeneity tests. A Random Forests classifier algorithm was also used to identify useful or important molecular classifiers. RESULTS: Overall, there were 25 significantly differentially expressed markers when comparing ATCs with DTCs. These included 5 of the 8 markers that were previously identified as being altered during anaplastic transformation and 3 additional markers were also found to be highly significantly differentially expressed by ATCs and DTCs. Clustering and classification analysis based on the previously identified 8-marker transformation panel, or the 5 of these markers that were found to be most important in the current study, readily separated DTC and ATC with a high degree of accuracy. CONCLUSIONS: The markers observed to change during thyroid cancer progression validate prior observations and represent promising molecular diagnostic or prognostic tools and identify targets for therapy of ATC. © 2011 Elsevier Inc. All rights reserved. KEYWORDS: Anaplastic thyroid cancer; Differentiated thyroid cancer; Anaplastic transformation; Thyroid cancer; Thyroid cancer progression; Molecular markers Anaplastic thyroid cancer (ATC) is considered one of the most aggressive and lethal solid tumors that is diagnosed in humans. Apart from its rapid and destructive local growth, approximately half of individuals diagnosed with ATC will have metastatic disease present at the time of their diagno- sis, and another 25% will develop metastases during the course of their disease. The prognosis for individuals diag- nosed with ATC is dismal, with median survival ranging from 4 to 12 months. 1 Fortunately, ATC accounts for only a small proportion of thyroid cancer diagnoses, with a recent review of the Surveillance, Epidemiology and End Results * Corresponding author. Tel.: 604-806-9108; fax: 604-806-9957. E-mail address: smwiseman@providencehealth.bc.ca Manuscript received November 9, 2010; revised manuscript January 24, 2011 0002-9610/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2011.01.010 The American Journal of Surgery (2011) 201, 580 –586