Topoisomerase II a and telomerase expression in papillary thyroid carcinomas L. Karayan-Tapon a , E. Menet b , J. Guilhot c , P. Levillain b , C.J. Larsen a , J.L. Kraimps d, * a Laboratoire de Prote ´ines et Inflammation, CHU la Mile ´trie, 86021 Poitiers Cedex, France b Service d’Anatomie et Cytologie—Pathologiques, CHU la Mile ´trie, 86021 Poitiers Cedex, France c Service d’Oncologie He ´matologique et The ´rapie Cellulaire, CHU la Mile ´trie, 86021 Poitiers Cedex, France d Service de Chirurgie Visce ´rale et Endocrinienne, CHU la Mile ´trie, 86021 Poitiers Cedex, France Accepted for publication 7 October 2003 KEYWORDS Topoisomerase II a; Telomerase; Papillary thyroid carcinoma; Tumour marker Summary Background. Altered topoisomerase II a (Topo II a) expression and telomerase activity (TA) reflect tumour cell growth and malignant transformation. Methods. We examined TA by using a TRAP assay and expression of Topo II a by immunohistochemical analysis in a series of 27 cases of papillary thyroid carcinoma (PTC). Results. Topo II a labelling index (LI) ranged from 0.1 to 4.2% and was significantly associated with patient age (r ¼ 20:42; p ¼ 0:003), with higher levels of Topo II a in patients under 40 years. There was no relationship between Topo II a LI, AGES score or other clinical outcome. TA was detected in 14 PTC, with relative levels ranging from 1.2 to 102 units. A significant positive correlation between the multiplicity of tumoral foci and the TA levels ðp , 10 22 Þ was noted. Conclusion. We concluded that Topo II a cannot be used as a marker of tumour aggressiveness. Furthermore, enhanced Topo II a expression in PTCs from patients less than 40 years old suggests that this age group might benefit from Topo II inhibitor chemotherapy. Q 2003 Elsevier Ltd. All rights reserved. Introduction Papillary thyroid carcinoma (PTC) has a variable clinical course. 1–4 The topoisomerase II (Topo II) enzymes are required in many aspects of DNA metabolism including replication, transcription, chromosome segregation and cell proliferation. 5 Two Topo II iso-enzymes, Topo II a and Topo II b, have been characterized in mammalian cells. 6–8 The expression of Topo II a has been associated with the rate of tumour cell proliferation. 9–12 Topo II a may be frequently expressed in thyroid tumours that are associated with aggressive clinical beha- vior. 13 The labelling index (LI) of Topo II a in tall cell variant forms of PTCs is much higher than in common papillary carcinoma. Telomerase activity (TA) may also have clinical significance in a variety of cancers. 14 Normal somatic cells have a limited proliferation capacity in the absence of telomerase activity as the 0748-7983/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2003.10.002 EJSO (2004) 30, 73–79 www.ejso.com *Corresponding author. Tel.: þ 33-5-49-44-42-41; fax: þ33-5- 49-44-41-19. E-mail address: j.l.kraimps@chu-poitiers.fr