6th ICHNO Abstract Book

page 48 6 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 16 – 18 March 2017 Barcelona, Spain __________________________________________________________________________________________ patients about the important implications of HPV positivity. 6th ICHNO

pathway has a different transcription regulation according to the tumor implantation site. The jugal submucosa location showed increased expression of AKT3, PDK1, PDK2, PRKCA, IGF1R, MAPK3/ERK1, CTNNB1 (1.5x higher), and decreased expression of FASL and NFKB1A (0.5x higher). These results with IHC unstaining of pmTOR indicate that in jugal submucosa MAPK/ERK pathway has a critical role in carcinogenesis. Conclusion Our preliminary results suggest that tumor microenvironment determines different gene expression and immunophenotypic profile in OSCC. In tongue the PI3K/AKT/mTOR pathway appears to have a determinant role whereas in jugal submucosa the ERK/MAPK pathway maybe a preferential target. PO-101 Osteopontin (OPN) as an instant, predictive marker of tumour hypoxia in head and neck cancer patients J. Mrochem-Kwarciak 1 , T. Rutkowski 2 , A. Wygoda 2 , R. Deja 1 , A. Hajduk 2 , Ł. Boguszewicz 3 , P. Widłak 4 , K. Składowski 2 1 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, ANALYTICS AND CLINICAL BIOCHEMISTRY DEPARTMENT, Gliwice, Poland 2 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, I Radiation and Clinical Oncology Department, Gliwice, Poland 3 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Medical Physics, Gliwice, Poland 4 Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Center for Translational Research and Molecular Biology of Cancer, Gliwice, Poland Purpose or Objective Despite of well known prognostic factors like locoregional stage of disease, there is still lack of markers describing individual feature of the tumor. Some of proinflammatory cytokines are supposed to predict the nature of the tumor what may help to optimize the therapy. Plasma osteopontin (OPN) is a putative marker of tumor hypoxia in patients with head and neck squamous cell carcinomas (HNSCC). Additionally, OPN has been recognized as important in the processes of tumorigenicity and metastasis. The aim of the study was to assess clinical utility of OPN as the biomarker of treatment outcome of radiotherapy (RT) or radiochemotherapy (CHRT) in HNSCC. Material and Methods Between 01/2009 and 08/2013 251 patients in the mean age of 59 years with squamous cell carcinoma of oropharynx (39%), hypopharynx (13%), larynx (44%) or oral cavity (4%) were treated with RT alone (48%) or combined with chemotherapy (52%). The median duration of symptoms prior the treatment was 33 months (range: 1 – 70). The stage of disease was determined due to a TNM scale. There were 15 (6%), 112 (45%), 74 (29%), and 50 (20%) patients with T1, T2, T3 and T4 tumor stage, respectively, and 99 (40%), 26 (10%), 105 (42%), and 21 (8%) patients with N0, N1, N2 and N3 nodal stage of disease, respectively (no patients with distant metastases were included). OPN was indicated in plasma before treatment and immediately after treatment completion. In statistic overview of the results STATISTICA 9.1 (StatSoft) program was used. While interpreting the results median value was used. U Mann-Whitney test was used for analysis of correlation between protein concentration and the stage of the disease. Multivariate Cox analysis of factors related to OS was carried on. Log- rank test was used to compare OPN as categorized value acc. to median respectively. Results

PO-100 Oral cancer microenvironment - PI3K/AKT/mTOR and ERK/MAPK pathways dependent targets C. Domingues 1,2,3 , M. Laranjo 3,4 , A.M. Abrantes 3,4 , A.B. Sarmento-Ribeiro 2 , L. Carvalho 3,5 , M.F. Botelho 3,4 , H. Silva 3,6 , M. Dourado 1,2,3 1 Faculty of Medicine- University of Coimbra- Portugal, Pathophysiology Curricular Unit- Dental Medicine, Coimbra, Portugal 2 Faculty of Medicine- University of Coimbra- Portugal, Laboratory of Oncobiology and Hematology- Applied Molecular Biology and University Clinic of Hematology, Coimbra, Portugal 3 Faculty of Medicine- University of Coimbra- Portugal, Center of Investigation on Environment Genetics and Oncobiology CIMAGO, Coimbra, Portugal 4 Faculty of Medicine- University of Coimbra- Portugal, Biophysics Institute- Institute for Biomedical Imaging and Life Sciences IBILI, Coimbra, Portugal 5 Faculty of Medicine- University of Coimbra- Portugal, Institute of Anatomical and Molecular Pathology, Coimbra, Portugal 6 Faculty of Medicine- University of Coimbra- Portugal, Medical Genetics Institute, Coimbra, Portugal Purpose or Objective Oral cancer represents 30% of all head and neck cancer and over 95 % are squamous cell carcinomas (OSCC). The anatomy of the oral cavity is particularly challenging due to different microenvironments identified in this relatively small area. Thus, the interplay between tumor cells and stromal structure has been receiving growing attention as it can contribute for malignant transformation. The PI3K/AKT/mTOR and the ERK/MAPK pathways regulate cell survival, proliferation, and motility and can converge to regulate each other. The aim of our study is to understand the role of PI3K/AKT/mTOR and ERK/MAPK in oral cancer microenvironment, namely in the reciprocal interplay between malignant cells and stromal structure, in order to identify new diagnosis and therapeutic targets for OSCC. Material and Methods For this purpose, the human OSCC cell line, HSC-3, was cultured. Then, approximately 3, 15 or 30 million were inoculated in Balb/c nu/nu mice (4/location) on tongue, on jugal submucosa and on dorsal side subcutaneously (back), respectively (Of. 3-CE-2011 FMUC, Portugal). During 3-7 weeks, the mice were supervised. After, they were killed by anesthetic overdose and tumor nodules and involving tissue were excised for ex vivo studies. The histology was assessed by the hematoxylin-eosin staining. The immunophenotype was evaluated by immunohistochemistry (IHC) using AE1AE3 cytokeratin cocktail, Vimentin, phospho(p)mTOR and Ki67. For genetic studies the samples were Purezol® processed and the obtained RNA was converted to cDNA and a 48 RT-PCR array for PI3K/AKT/mTOR pathway specific for human was applied. Results Our results showed that depending on the inoculation/implantation site HSC-3 cells exhibit different gene expression and immunophenotype profile as well as different amount of keratinizing cells, large cells and basal/intermediate cells. Tongue location showed increased IHC expression of AE1/AE3, Vimentin and pmTOR comparing with the other models. The Ki67 index was higher in large and basal cells in all models. The gene expression profile showed that the PI3K/AKT/mTOR