Bcl-Xl protein expression in laryngeal squamous cell carcinoma T. KRECICKI,  M. FRACZEK,  J. KOZLAK, y T. ZATONSKI,  M. JELEN z & D. DUS y  Department of Otolaryngology, Wroclaw Medical University, yInstitute of Immunology and Experimental Therapy, Polish Academy of Science and zDepartment of Pathological Anatomy, Wroclaw Medical University, Wroclaw, Poland Accepted for publication 10 June 2003 KRECICKI T., FRACZEK M ., KOZLAK J ., ZATONSKI T., JELEN M . & DUS D . (2004) Clin. Otolaryngol. 29, 55±58 Bcl-X1 protein expression in laryngeal squamous cell carcinoma The Bcl-2 family of proteins regulate one of the steps in an evolutionary conserved apoptotic pathway. The long splice variant of Bcl-X (Bcl-Xl) is a potent antagonist of apoptosis. The aim of the study was to evaluate the relation between the presence of immunohistochemically detectable Bcl-Xl protein in laryngeal squamous cell carcinomas (LSCCs) and clinicopathological data, as well as DNA ploidy status and proliferative activity. In 50 specimens of LSCC, Bcl-Xl protein expression was evaluated immunohistochemically. Proliferative activity (SG 2 M-phase index) and DNA ploidy were measured by ¯ow cytometry. In our study, Bcl-Xl protein expression decreased with decreasing tumour differentiation (P  0.04). The majority of patients with Bcl-Xl protein immunoreactivity had no metastatic lymph node involvement (P  0.01). Other factors such as age, gender, primary tumour size (pT) and type of cancer (keratinizing/non-keratinizing) were not associated with Bcl-Xl protein level. There was no correlation between Bcl-Xl protein and SG 2 M-phase index or DNA ploidy status. Our ®ndings show that expression of Bcl-Xl protein is increased in a great fraction of laryngeal cancers. Further studies, however, are needed to clarify association between Bcl-Xl protein expression and clinical course of patients. Keywords Bcl-Xl protein immunohistochemistry proliferative activity DNA ploidy laryngeal cancer Expansion of neoplastic epithelial cells results not only from increased rates of cell proliferation, but also from decreased rates of cell death because of apoptosis. The Bcl-2 family of proteins regulate one of the steps in an evolutionary conserved apoptotic pathway. 1 Some of these (Bcl-2, Mcl-1, Bcl-Xl and A1) inhibit, whereas others (Bax, Bak, Bad and Bcl-Xs) promote programmed cell death. Imbalance in this physiolo- gical equilibrium results in prevention of normal cell cycle turnover and can lead to accumulation of oncogenic mutations and contribute to carcinogenesis. 2 It is known that overexpres- sion of transforming oncogenes in the absence of apoptotic inhibition triggers apoptosis ef®ciently. The long splice variant of Bcl-X (Bcl-Xl) is a 241-aa protein, potent antagonist of apoptosis, whereas the short splice variant (Bcl-Xs) has opposing function and acts to promote apoptosis. 3 However, Bcl-2 and Bcl-Xl proteins are identical in 47%; Bcl-Xl expression pattern seems to be different from that of Bcl-2, suggesting that these genes promote survival in a tissue-speci®c manner. Expression of Bcl-Xl is widespread in human tissues which supports its important role in the regulation of cell cycle. 4 Overexpression of the Bcl-Xl gene has been detected in many tumours of different origin. 5±7 It is known that over- expression of Bcl-2 or Bcl-Xl in cell culture provides protection against a variety of apoptotic insults, e.g. growth factor depri- vation, oncogene (c-myc), tumour suppressor gene (p53), cyto- lytic T-cells, etc. 1 Enhanced Bcl-2 family gene expression can confer resistance to chemo- and radiotherapy. 8 Moreover, Bcl-2 protooncogene synergizes with the c-myc oncogene in tumour progression, speci®cally blocking c-myc-induced apoptosis without preventing c-myc-dependent cell proliferation. 9 The aim of the study was to evaluate the relation between the presence of immunohistochemically detectable Bcl-Xl protein in laryngeal squamous cell carcinomas (LSCCs) and clinicopathological data, as well as DNA ploidy status and proliferative activity. Materials and methods Tumour samples were obtained from 50 patients (2 women, 48 men) with laryngeal cancer, having laryngeal surgery in the Department of Otolaryngology, Wroclaw Medical University, Clin. Otolaryngol. 2004, 29, 55±58 # 2004 Blackwell Publishing Ltd 55 Correspondence: Tomasz Krecicki, Department & Clinic of Otolaryngology, Chalubinskiego Street 2, 50-368 Wroclaw, Poland (e-mail: krecicki@orl.am.wroc.pl).