CLINICAL STUDY High prevalence of cyclooxygenase 2 expression in papillary thyroid carcinoma Chung-Yau Lo, Kin-Yin Lam 1 , Pauline P Leung and John M Luk Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam Road, Hong Kong China and 1 Discipline of Pathology, School of Medicine, Griffith University, Goldcoast, Australia (Correspondence should be addressed to Chung Yau Lo; Email: cylo@hkucc.hku.hk) Abstract Background: Cyclooxygenase-2 (COX-2) seems to play a role in the development and carcinogenesis of papillary thyroid carcinoma. Its incidence of expression and potential application as a tumor marker remain to be elucidated. Materials and methods: Immunohistochemical staining for COX-2 expression was performed for 30 papillary thyroid carcinoma (PTC) and 40 benign thyroid specimens. COX-2 mRNA expression was analyzed using a reverse transcriptase-polymerase chain reaction (RT-PCR) for paired fresh frozen tis- sues removed from surgically resected PTC specimens. Results: COX-2 expression was detected by immunohistochemistry in 27 of 30 (90%) PTC but was absent in 40 benign thyroid specimens, including 27 nodular hyperplasia, 7 follicular adenoma and 6 lymphocytic thyroiditis. Two of the three COX-2 negative carcinomas were follicular variant of PTC. RT-PCR analysis confirmed COX-2 mRNA over-expression in 14 of 20 (70%) paired specimens of PTC. Real-time quantitative RT-PCR showed that the level of COX-2 mRNA expression was signifi- cantly higher in PTC than in both the adjacent non-cancerous tissues and the benign thyroid specimens. Conclusion: COX-2 is frequently expressed in PTC but not in benign thyroid specimens. COX-2 expression may serve as a useful molecular marker for PTC in cases of diagnostic difficulty. European Journal of Endocrinology 152 545–550 Introduction Cylcooxygenases catalyze the formation of prostaglan- dins from arachidonic acid and two cyclooxygenase iso- forms, COX-1 and COX-2, have been identified. COX-1 is known as a housekeeping gene and is ubiquitously expressed in most tissues. On the other hand, COX-2 is an early expressed gene and is induced by various sti- mulating factors such as growth factors, oncogenes and cytokines. Recent studies have demonstrated that COX-2 plays a role in carcinogenesis and carcinoma progression in many epithelial tumors including thyr- oid carcinomas (1–6). The expression of COX-2 in human thyroid cancer cell lines as well as in benign and malignant thyroid tissues has been studied (6). The finding that COX-2 is upregulated in human thyroid cancer but not in benign thyroid nodules suggests that COX-2 expression may serve as a marker for thyroid malig- nancy and may have an important role during the development of thyroid cancer (6). However, the fre- quencies of COX-2 expression vary widely in different types of thyroid cancers (6–11) and COX-2 expression is also detected in a small proportion of benign thyroid tissues, especially follicular adenoma and Hashimoto thyroiditis (8–11). The usefulness of COX-2 as a marker of thyroid malignancy has been challenged (8) but its potential role in carcinogenesis continues to arouse significant interest (6–11). Despite its clini- cal heterogeneity, papillary thyroid carcinoma (PTC) is characterized by a consistent set of molecular changes different from other types of thyroid cancer. COX-2 seems to be upregulated in PTC but not in other thyr- oid carcinomas. In this study, we have examined a relatively large number of PTC and benign thyroid specimens for COX-2 expression using immunohisto- chemistry in order to assess the feasibility of using COX-2 as a marker for malignancy. The level of COX-2 mRNA expression was analyzed and compared between malignant, adjacent normal and benign thyr- oid tissues. Materials and methods Immunohistochemistry Paraffin blocks of thyroid specimens surgically excised from 70 patients were selected for the present study. These included 30 PTC and 40 benign thyroid specimens. There were 17 men and 53 women. European Journal of Endocrinology (2005) 152 545–550 ISSN 0804-4643 q 2005 Society of the European Journal of Endocrinology DOI: 10.1530/eje.1.01883 Online version via www.eje-online.org