Anni Sjöblom1, Ulf-Håkan Stenman2, Jaana Hagström1,3,4, Lauri Jouhi5, Caj Haglund3,6, Stina Syrjänen4,7, Petri Mattila5, Antti Mäkitie5,8,9, Timo Carpén1,5,9. 1. Department of Pathology, University of Helsinki and HUS Helsinki University Hospital, P.O. Box 21, FI-00014 Helsinki, Finland. 2. Department of Clinical Chemistry, University of Helsinki and HUS Helsinki University Hospital, P.O. Box 63, FI-00014 Helsinki, Finland. 3. Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, FI-00014 Helsinki, Finland. 4. Department of Oral Pathology and Oral Radiology, University of Turku, Lemminkäisenkatu 2, FI-20520 Turku, Finland. 5. Department of Otorhinolaryngology-Head and Neck Surgery, University of Helsinki and HUS Helsinki University Hospital, P.O. Box 263, FI-00029 Helsinki, Finland. 6. Department of Surgery, University of Helsinki and HUS Helsinki University Hospital, P.O. Box 440, FI-00029 Helsinki, Finland. 7. Department of Pathology, Turku University Hospital, Kiinamyllynkatu 10, FI-20520 Turku, Finland. 8. Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska Hospital, SE-171 76 Stockholm, Sweden. 9. Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, P.O. Box 63, FI-00014 Helsinki, Finland.
Abstract
BACKGROUND: We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. MATERIALS AND METHODS: The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012-2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A significant correlation was found between S-TATI positivity and poor OS (p < 0.001) and DSS (p = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (p = 0.01) and DSS (p = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (p = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (p < 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. CONCLUSION: Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.
BACKGROUND: We studied the role of tumor-associated trypsin inhibitor (TATI) in serum and in tumor tissues among human papillomavirus (HPV)-positive and HPV-negative OPSCC patients. MATERIALS AND METHODS: The study cohort included 90 OPSCC patients treated at the Helsinki University Hospital (HUS), Helsinki, Finland, in 2012-2016. TATI serum concentrations (S-TATIs) were determined by an immunofluorometric assay. Immunostaining was used to assess tissue expression. HPV status was determined with a combination of p16 immunohistochemistry and HPV DNA PCR genotyping. The survival endpoints were overall survival (OS) and disease-specific survival (DSS). RESULTS: A significant correlation was found between S-TATI positivity and poor OS (p < 0.001) and DSS (p = 0.04) in all patients. In HPV-negative cases, S-TATI positivity was linked to poor OS (p = 0.01) and DSS (p = 0.05). In HPV-positive disease, S-TATI positivity correlated with poor DSS (p = 0.01). S-TATI positivity was strongly associated with HPV negativity. TATI serum was negatively linked to a lower cancer stage. TATI expression in peritumoral lymphocytes was associated with favorable OS (p < 0.025) and HPV positivity. TATI expression in tumor and in peritumoral lymphocytes correlated with lower cancer stages. CONCLUSION: Our results suggest that S-TATI positivity may be a biomarker of poor prognosis in both HPV-positive and HPV-negative OPSCC.