Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition

Intestinal-type adenocarcinoma (ITAC) of sinonasal tract is a rare malignant tumor with strong morphological, immunophenotypical, and molecular similarities to colorectal adenocarcinoma (CRC). Tumor budding (TB) is a well-established adverse prognostic marker in CRC and some head and neck tumors, with features of epithelial-mesenchymal transition (EMT). The aim of this study was to assess TB in ITAC and to evaluate its possible association with EMT markers in this setting. We selected 32 surgically resected specimens of non-mucinous/non-signet ring ITAC and evaluated them for TB according to the international recommendations developed for CRC. The expression of the EMT markers E-cadherin, ZEB1, ZEB2, SLUG, and SNAIL was evaluated by immunohistochemistry (IHC). Results were stratified using clinical and follow-up data (2/32 patients had metastatic disease and 4/32 died of disease). We observed TB in 13/32 (40.6%) ITAC cases including the 7 patients with relapse (p = 0.0005) and the 4 patients dead of disease (p = 0.02). Lymphovascular invasion was associated with TB (p = 0.008). Absence of TB was associated with low ZEB2 expression (p = 0.003). No other association with EMT markers emerged. Occupational exposure to wood and leather dust was not related to the presence of TB. TB interobserver concordance was substantial (proportion of agreement = 87%; Cohen's kappa = 0.73). This work suggests that TB is associated with a worse prognosis in ITAC, but our findings do not seem to support the involvement of EMT in this specific setting. Further larger studies are needed to address this point.