PMID- 28730788 OWN - NLM STAT- MEDLINE DCOM- 20190712 LR - 20190712 IS - 1107-0625 (Print) IS - 1107-0625 (Linking) VI - 22 IP - 3 DP - 2017 May-Jun TI - Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis. PG - 771-776 AB - PURPOSE: Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. METHODS: Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. RESULTS: Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. CONCLUSIONS: Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents. FAU - Papadas, Theodoros A AU - Papadas TA AD - Department of Otorhinolaryngology, Head and Neck Surgery, Medical School, University of Patras; Patras, Greece. FAU - Tsiambas, Evangelos AU - Tsiambas E FAU - Mastronikolis, Nicholas S AU - Mastronikolis NS FAU - Karameris, Andreas AU - Karameris A FAU - Mastronikolis, Stylianos N AU - Mastronikolis SN FAU - Papadas, Athanasios T AU - Papadas AT FAU - Fotiades, Panagiotis P AU - Fotiades PP FAU - Ragos, Vasileios AU - Ragos V LA - eng PT - Journal Article PL - Cyprus TA - J BUON JT - Journal of B.U.ON. : official journal of the Balkan Union of Oncology JID - 100883428 RN - EC 5.99.1.2 (DNA Topoisomerases, Type I) SB - IM MH - DNA Topoisomerases, Type I/analysis/genetics/*physiology MH - Female MH - Humans MH - Laryngeal Neoplasms/*enzymology MH - Male MH - Squamous Cell Carcinoma of Head and Neck/*enzymology MH - Tissue Array Analysis/*methods EDAT- 2017/07/22 06:00 MHDA- 2019/07/13 06:00 CRDT- 2017/07/22 06:00 PHST- 2017/07/22 06:00 [entrez] PHST- 2017/07/22 06:00 [pubmed] PHST- 2019/07/13 06:00 [medline] PST - ppublish SO - J BUON. 2017 May-Jun;22(3):771-776.