Tumor-Associated Trypsin Inhibitor (TATI) as a Biomarker of Poor Prognosis in Oropharyngeal Squamous Cell Carcinoma Irrespective of HPV Status

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.

The Role of Human Chorionic Gonadotropin Beta (hCGβ) in HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma

“…The study includes 90 patients with OPSCC from an existing database described in previous studies [ 20 , 21 ]. Patients with prospectively collected serum samples and established HPV statuses were admitted to the analysis.…”

“…In addition, we compared the S-hCGβ levels to the serum concentrations of tumor-associated trypsin inhibitor (S-TATI). The methodology of the S-TATI assay is described in our previous work [ 21 ].…”

“…The protocol for immunostaining is described in detail in our previous work [ 21 ]. We used a monoclonal anti-hCGβ antibody (MAb 9C11) produced in-house [ 25 ] as a primary antibody.…”