Virchows Arch (2005) 447: 12–17 DOI 10.1007/s00428-005-1235-1 ORIGINAL ARTICLE Miguel García-González . Ihab Abdulkader . Angel Vázquez Boquete . Xosé Manuel Lens Neo . Jerónimo Forteza . José Cameselle-Teijeiro Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the human thyroid gland Received: 5 November 2004 / Accepted: 16 February 2005 / Published online: 10 June 2005 # Springer-Verlag 2005 Abstract This study was undertaken to investigate cyclo- oxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immuno- histochemically in a total of 174 samples. COX-2 immu- noreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was ob- served in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p≤0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in com- parison with all papillary carcinomas (p≤0.05). However, we could not establish any relationships among COX-2, patients’ ages or lymph node metastases in papillary car- cinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undif- ferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carci- nomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the un- differentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to ra- diation in some studies. Keywords Cyclooxygenase-2 . Thyroid cancer . Papillary carcinoma . Undifferentiated carcinoma . Immunohistochemistry . In situ hybridisation Introduction There are two isoforms of cyclooxygenase (COX), COX-1 and COX-2, involved in the synthesis of prostaglandins from arachidonic acid [29]. The COX-1 enzyme is ex- pressed constitutively in most mammalian tissues where, although often undetected, it can be rapidly induced. The COX-2 gene is an early-response gene that is up-regulated by proinflammatory stimuli, growth factors, oncogenes and tumour-promoting phorbol esters [10, 13, 22]. COX-2 seems to play a role in carcinogenesis as well as in carcinoma progression; COX-2 is up-regulated in trans- formed cells [24], in colorectal cancers [20, 22], ulcerative colitis-associated neoplasia [1], hepatocellular carcinoma [14], oesophageal and gastric carcinomas [25, 34], pulmo- nary and mammary tumours [22], pancreatic cancer [27], renal cell carcinoma [11], prostate carcinoma [33] and pi- tuitary tumours [30]. COX-2 knockout mice also have a lower incidence of several tumour types including skin papillomas and intestinal polyps [2, 18, 26]. Epidemi- ological studies have also shown that chronic intake of non-steroidal anti-inflammatory drugs, which function as COX inhibitors, reduces the incidence of gastrointestinal cancer [8, 9, 32]. Enhanced expression of COX-2 in lymphocytic thyroid- itis and Hashimoto’ s thyroiditis suggests an important role of this enzyme in these inflammatory thyroid processes [5, 17]. Thyroid cancer of follicular cells includes several histological types of tumours with various molecular alterations and different clinical behaviours. Papillary car- cinoma is the most common malignant tumour of the thyroid and has a relatively indolent clinical course in contrast to the rapidly fatal course of anaplastic (undiffer- entiated) carcinoma [6]. Poorly differentiated carcinomas fall between well-differentiated (papillary and follicular) carcinomas and undifferentiated carcinomas in terms of M. García-González . X. M. L. Neo Department of Nephrology, Hospital Clínico Universitario, Choupana s/n, 15706 Santiago de Compostela, Spain I. Abdulkader . A. V. Boquete . J. Forteza . J. Cameselle-Teijeiro (*) Department of Pathology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Choupana s/n, 15706 Santiago de Compostela, Spain e-mail: apjocame@usc.es Tel.: +34-981-950858 Fax: +34-981-950889