7th ICHNO Abstract book

page 56 7 th ICHNO Conference International Conference on innovative approaches in Head and Neck Oncology 14 – 16 March 2019 Barcelona, Spain __________________________________________________________________________________________ 7th ICHNO

factor 4A-III, eukaryotic translation initiation factor 4H, cathepsin B; interleukin enhancer-binding factor 2, Ras GTPase-activating-like protein IQGAP1, sorbitol dehydrogenase and cathepsin D (p<0.01). KEGG ontology pathway enrichment was generated (Figure 2). Conclusion Our method was able to to identify a tumor profile related to local relapse in FFPE NPC samples. We found a tumor profiling of differentially expressed proteins, including a pool of nine proteins up-regulated as potential proteomic signature of local relapse or radioresistance. Validation is needed. PO-111 The use of a serum proteomic signature to improve HPV classification of OPSCC: A pilot study A. Dickinson 1 , M. Saraswat 2 , S. Joenväärä 2 , T. Carpén 1 , T. Tohmola 3 , P. Mattila 1 , C. Haglund 4 , J. Haagström 5 , A. Mäkitie 1,6 , S. Silén 1,7 1 University of Helsinki and Helsinki University Hospital, Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki, Finland; 2 University of Helsinki, Transplantation Laboratory, Helsinki, Finland; 3 University of Helsinki, Department of Biosciences, Helsinki, Finland ; 4 University of Helsinki and Helsinki University Hospital, Department of Surgery, Helsinki, Finland; 5 University of Helsinki and Helsinki University Hospital, Department of Pathology, Helsinki, Finland ; 6 Karolinska Institutet, Division of Ear- Nose and Throat Diseases- Department of Clinical Sciences- Intervention and Technology, Stockholm, Sweden; 7 Karolinska Institutet, Department of Biosciences and Nutrition, Stockholm, Sweden Purpose or Objective Whether or not human papillomavirus (HPV) has an aetiological role in the development of an oropharyngeal squamous cell carcinoma (OPSCC) affects the clinical features of the tumour and the patient’s prognosis. Currently, p16 immunohistochemistry is used in clinical routine in accordance with the 8 th AJCC TNM classification system. However, this can mis-classify patients as it has a specificity of 83%. The prognosis of p16-positive, DNA- negative tumours is worse than that of double positive tumours and thus, these patients may not be suitable for treatment de-escalation. Based on mass-spectrometry proteomics, our aim was to identify serum proteins that could improve classification of these patients in clinics that do not have the availability of HPV-DNA detection, which may improve the specificity of the results. Material and Methods Serum samples were taken from patients diagnosed with OPSCC at the Department of Otorhinolaryngology – Head and Neck Surgery, HUS Helsinki University Hospital, (Helsinki, Finland). Differently expressed serum proteins were identified and quantified using label free proteomics. Protein expressions were compared between patients with different combinations of p16-positive (p16+), p16-negative (p16-), HPV DNA-positive (DNA+) and HPV DNA-negative (DNA-) disease. HPV DNA was detected using PCR followed by ISH. The unpaired t-test p- values and area-under-the-curve (AUC) by receiver operating characteristics curve analysis (ROC) were calculated on a protein by protein basis. Results EGF-containing fibulin-like extracellular matrix protein 1 was almost twice as abundant in p16+DNA- tumours compared with p16+DNA+ tumours (AUC 0.87). Protein IGHV3OR16-9 was upregulated in p16-DNA+ compared with p16-DNA- (AUC 0.92). Galectin-3-binding protein and

of macrophages recruited to the tumor site are CD68+ CD163+ TAMs (p<0.0001). Conclusion The recruitment of macrophages is a strong prognostic factor for HNSCC, this recruitment being increased in HPV+p16+ patients and composed mostly by TAMs. PO-110 Potential proteomic profiling of local relapse in nasopharyngeal carcinoma from a non-endemic region E. Netto 1 , H. Santos 2 , L. Carvalho 2 , J.L. Capelo-Martínez 3 , M. Roldão 4 1 NOVA Medical School- Faculdade de Ciências Médicas- Universidade Nova de Lisboa, Radiation Oncology- IPOLFG, Lisboa, Portugal; 2 BIOSCOPE Research Group- LAQV- REQUIMTE, Department of Chemistry- Faculty of Science and Technology- Universidade NOVA de Lisboa- Campus de Caparica- Portugal., Caparica, Portugal; 3 BIOSCOPE Research Group- LAQV-REQUIMTE, PROTEOMASS Scientific Society- Madan Parque- Rua dos Inventores- 2825-182, Caparica, Portugal; 4 Instituto Português de Oncologia de Lisboa Francisco Gentil, Radiation Oncology, Lisbon, Portugal Purpose or Objective A minority of nasopharyngeal carcinoma (NPC) patients will develop local relapse that poses challenges to the multidisciplinary team. Our aim is to identify biomarkers related to local relapse in a non-endemic European cohort of patients. Material and Methods We performed a single-center retrospective study using formalin-fixed paraffin-embedded (FFPE) samples of untreated NPC patients. After ethics and board approvals, the samples were submitted to protein extraction followed by filter aided sample preparation (FASP), digestion and label-free quantitative mass spectrometry and bioinformatics via MaxQuant. Patients with inadequate FFPE material were excluded. Intensity- modulated radiation therapy (IMRT) was delivered as per RTOG0615. Concurrent and adjuvant chemotherapy was prescribed as per Integroup 0099. Patients’ clinical data from follow up were retrieved. Survival was estimated using Kaplan-Meier curves. Volcano plot and KEGG ontology graphics were generated to detect protein pathways. Results We found 53 patients, their characteristics at diagnosis were: 71% male; 96% Caucasian; 73% WHO grade 3; 44% T1, 14% T2, 21% T3 and 21% T4; 23% N0, 15% N1, 37% N2 and 25% N3; 94% M0. Complete stage were: 11.5% I, 11.5% II, 29% III, 19% IVA, 23% IVB and 6% IVC. The majority of patients were treated with concurrent chemoradiation followed by adjuvant chemotherapy (54%). With median follow up of 41.5 months for the whole cohort, 4 year local control was 83%, distant metastases free-survival was 77%. Out of 53 patients we found 9 patients with local relapse after NPC treatment. All relapses occurred in the highest dose volume (70Gy). Five were on T1, 2 on T3 and 2 on T4. Median time to local relapse was 16.5 months and 8 out 9 patients had relapses before 2 years of follow up. All 9 patients received reirradiation. Two patients died from local progression, three died from distant metastases and the remaining 4 patients are alive with no evidence of disease. We found 58 differentially expressed proteins on patients with local relapse (p<0.01, Figure 1). Forty-nine proteins were up-regulated on patients with local relapse. Another pool with 9 proteins were found to be down- regulated in relapsed patients: profilin-1, interferon- induced GTP-binding protein Mx1, eukaryotic initiation

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