Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival.

Nima Attaran,Karin Nylander,Nicola Sgaramella,Philip J Coates,Torben Wilms,Lixiao Wang,Xiaolian Gu,Robin Fåhraeus,Linda Boldrup,Katarina Zborayova

doi:10.3390/ijms21176220

Abstract

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

Highlights

In Sweden, approximately 160 new cases of squamous cell carcinoma of the tongue (SCCOT) are detected annually, making it the most frequent tumor in the oral cavity
Based on our previous findings of an increased cytolytic activity in tumor-free tongue tissue contralateral to an SCCOT [6] remaining in the patient after treatment, we focused on transporter associated with antigen processing (TAP) expression in these tissues
For TAP2, there was no significant difference in mRNA between tumor-free and healthy controls (Figure 1B), whereas a significant correlation between TAP1 and TAP2 levels was seen (Figure 1C)

Summary

Introduction

In Sweden, approximately 160 new cases of squamous cell carcinoma of the tongue (SCCOT) are detected annually, making it the most frequent tumor in the oral cavity. When surgically removing an oral cancer, seemingly benign epithelium preconditioned to develop into cancer is left behind [3]. This could help explain the high incidence of local recurrence and multiple second primary tumors seen in patients with SCCOT and other types of squamous cell carcinoma of the head and neck (SCCHN). Genetically altered fields in the case of intraoral SCC can be detected as far as 7 cm from the tumor, implying that, clinically normal, the main part of the oral cavity is affected by genetic alterations [4]. In the case of SCCOT, it can be of value to study the tumor itself and the clinically tumor-free adjacent tongue tissue in order to map changes indicative of a tumor, novel or relapse, before any clinical signs are present

Methods

Results

Conclusion