Eur Arch Otorhinolaryngol (2007) 264:923–928 DOI 10.1007/s00405-007-0276-2 123 HEAD AND NECK Expression patterns of cyclin E, cyclin A and CDC25 phosphatases in laryngeal carcinogenesis Marcin Fraczek · Zdzislaw Wozniak · David Ramsey · Tomasz Krecicki Received: 19 October 2006 / Accepted: 10 January 2007 / Published online: 15 March 2007  Springer-Verlag 2007 Abstract The aim of the research was to evaluate the expression levels of cyclin E/A and CDC25A/B during laryngeal carcinogenesis. The expression was demonstrated using immunohistochemistry in 46 cases of laryngeal can- cer (LSCC), 23 epithelial dysplasias (ED) and 21 samples of normal mucosa (NM). The mean labeling indices (LI) for cyclin E in LSCC, ED and NM were 10.6, 4.9 and 0%; for cyclin A 27.2, 17.5 and 7%; for CDC25A 73.9, 53 and 32% and for CDC25B 36.5, 25.9 and 0%, respectively. A gradual increase in cyclin A and CDC25A expression lev- els from mild through moderate and severe dysplasia to in situ carcinoma were noted. Cyclin A LI signiWcantly increased also from NM through ED to LSCC. Cyclin A and CDC25A LI signiWcantly increased from NM to ED. Overexpression of cyclin A and CDC25A was signiWcantly associated with proliferation among ED. Linear interdepen- dency was detected in ED between the expression of CDC25A and cyclin A. Cyclin E and CDC25B overexpres- sion occurs as a late event in neoplastic transformation. The progressive expression of proteins supports the multistep model of laryngealcarcinogenesis. The results indicate a possible role of cyclin A as a marker reXecting cell prolifer- ation. The enhanced immunoexpression of cyclin A and CDC25A suggests the potential for malignant formation in preneoplastic lesions. Keywords Cyclin E · Cyclin A · CDC25A · CDC25B · Laryngeal dysplasia · Laryngeal cancer Introduction Deregulation of cell cycle control seems to be one of the most important events in the pathogenesis of cancer. Tran- sitions in the cell cycle of higher eukaryotic cells are gov- erned by a family of cyclin-dependent kinases (CDKs). CDKs are regulated by a combination of factors, including cyclin association, phosphorylation and dephosphorylation of the CDK subunit. Cyclins are periodically transcribed and degraded pro- teins, which promote cell-cycle progression in a phase- speciWc manner by associating with their enzymatically active partners, the cyclin-dependent kinases. Cyclin E is expressed in the middle of G1 and ends at the beginning of the S phase. The activity of cyclin E is crucial to enter the S phase and start nuclear DNA replication [1]. Induced cyclin E expression leads to accelerated G1/S transition even when accompanied by low phosphorylated pRb and/or by inactivated E2F transcription factor. It results also in an elongated S phase duration, which subsequently leads to increased chromosomal instability that often marks laryn- geal oncogenesis [2]. In cyclin E deWcient mice, it was shown that cyclin E expression is essential for oncogenic transformation, which indirectly supports the function of cyclin E as an oncogene [3]. Cyclin A is expressed from M. Fraczek (&) · T. Krecicki Department of Otolaryngology, Wroclaw Medical University, Chalubinskiego Street 2, 50-368, Wroclaw, Poland e-mail: raucedo@wp.pl Z. Wozniak Department of Pathological Anatomy, Wroclaw Medical University, Marcinkowskiego Street 1, 50-368, Wroclaw, Poland D. Ramsey Institute of Mathematics and Computer Science, Wroclaw University of Technology, Wybrzeze Wyspianskiego Street 27, 50-370, Wroclaw, Poland