PMID- 30275203 OWN - NLM STAT- MEDLINE DCOM- 20181011 LR - 20221207 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 38 IP - 10 DP - 2018 Oct TI - Comparative p16(IKN4A) Expression in Laryngeal Carcinoma and Cervical Cancer Precursors: A Real-time Grid-based Immunocytochemistry Analysis. PG - 5805-5810 LID - 10.21873/anticanres.12920 [doi] AB - BACKGROUND/AIM: p16 (gene locus: 9p21) tumor suppressor gene is considered an important biomarker for the progression and prognosis in a variety of malignancies and pre-cancerous lesions, including high-risk (HR-) human papilloma virus (HPV)-mediated squamous intraepithelial lesions (SILs), based on cytological and the corresponding cervical intraepithelial neoplasia (CIN) histopathological categorization. p16 acts as a cyclin-dependent kinase-4 inhibitor negatively regulating the cell cycle. In persistent HPV infection, E7 oncogenic protein binds retinoblastoma protein leading to its proteolytic transformation, also triggering E2F dissociation, which increases DNA transcription and progression to S phase. This mechanism promotes aberrant p16 over-expression. Our aim was to comparatively analyze p16 protein expression patterns in laryngeal squamous cell carcinomas (LSCC) and also in SILs. MATERIALS AND METHODS: Fifty (n=50) primary LSCCs tissues all non-HPV-dependent, and a set of 50 liquid-based SILs, were analyzed by immunohistochemistry and immunocytochemistry, respectively. Concerning the screening process in cytological slides, a novel real-time reference and calibration grid platform was implemented and employed. RESULTS: Decreased protein expression was observed in 34/50 (68%) tissues regarding LSCCs. Overall p16 expression was associated to smoking status of the patients (p=0.001), and also with the p-stage of the examined malignancies (p=0.033). A strong statistical significance was assessed correlating LSIL/HSIL cases with a progressive p16 over expression (p=0.001), also reflecting a higher CIN diagnosis (p=0.001). CONCLUSION: p16 down-regulation is a frequent genetic event in LSCCs, which is associated with advanced disease. In contrast to this, p16 over-expression triggered by a specific molecular mechanism shows a strong relationship with a progressively aggressive phenotype due to upgraded SIL/CIN cervical categorization. The first described application of the grid platform demonstrated a considerable improvement in the immunocytochemistry slide screening process enhancing the diagnostic reliability. CI - Copyright(c) 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Tsiambas, Evangelos AU - Tsiambas E AD - Department of Pathology-Cytology, 401 GA Hospital, Athens, Greece tsiambasecyto@yahoo.gr. AD - Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece. FAU - Riziotis, Christos AU - Riziotis C AD - Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, Athens, Greece. FAU - Mastronikolis, Nicholas S AU - Mastronikolis NS AD - ENT Department, Medical School, University of Patras, Patras, Greece. FAU - Peschos, Dimitrios AU - Peschos D AD - Department of Physiology, Medical School, University of Ioannina, Ioannina, Greece. FAU - Mortakis, Alexandros AU - Mortakis A AD - LITO and IASO-REA, Private Gynaecological Centers, Athens, Greece. FAU - Kyroysis, Grigorios AU - Kyroysis G AD - LITO and IASO-REA, Private Gynaecological Centers, Athens, Greece. FAU - Mastronikolis, Stylianos N AU - Mastronikolis SN AD - Department of Medicine, School of Health Sciences, University of Crete, Heraklion, Greece. FAU - Batistatou, Anna AU - Batistatou A AD - Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece. FAU - Lazaris, Andreas C AU - Lazaris AC AD - Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece. FAU - Patsouris, Efstratios AU - Patsouris E AD - Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece. FAU - Ragos, Vasileios AU - Ragos V AD - Department of Maxillofacial, Medical School, University of Ioannina, Ioannina, Greece. LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) SB - IM MH - Biomarkers, Tumor/*metabolism MH - Carcinoma, Squamous Cell/*metabolism/pathology MH - Cyclin-Dependent Kinase Inhibitor p16/*metabolism MH - Female MH - Follow-Up Studies MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*metabolism/pathology MH - Male MH - Prognosis MH - Squamous Intraepithelial Lesions of the Cervix/*metabolism/pathology MH - Uterine Cervical Neoplasms/*metabolism/pathology MH - Uterine Cervical Dysplasia/*metabolism/pathology OTO - NOTNLM OT - cervical intraepithelial neoplasia OT - grid platform OT - histological categorization OT - laryngeal squamous cell carcinoma OT - p16 OT - squamous intraepithelial lesion EDAT- 2018/10/03 06:00 MHDA- 2018/10/12 06:00 CRDT- 2018/10/03 06:00 PHST- 2018/08/31 00:00 [received] PHST- 2018/09/22 00:00 [revised] PHST- 2018/09/24 00:00 [accepted] PHST- 2018/10/03 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] AID - 38/10/5805 [pii] AID - 10.21873/anticanres.12920 [doi] PST - ppublish SO - Anticancer Res. 2018 Oct;38(10):5805-5810. doi: 10.21873/anticanres.12920.