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

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Abstract

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.

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Acknowledgments

The preliminary results of this study were presented at the 31st European Congress of Pathology that was held in Nice, France, September 2019. The authors are grateful to Martina Boscolo Bielo for her contribution to statistical analyses.

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Author notes

  1. Valeria Maffeis and Rocco Cappellesso contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Via Aristide Gabelli, 61, 35121, Padua, Italy

    Valeria Maffeis, Rocco Cappellesso, Francesca Galuppini, Vincenza Guzzardo & Ambrogio Fassina

  2. Department of Neurosciences, Otorhinolaryngology Section, University of Padova, Padua, Italy

    Alessia Zanon, Diego Cazzador, Enzo Emanuelli & Alessandro Martini

  3. Department of Neurosciences, Section of Human Anatomy, University of Padova, Padua, Italy

    Diego Cazzador

  4. Department of Statistics, University of Padova, Padua, Italy

    Laura Ventura

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  1. Valeria Maffeis
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Correspondence to Valeria Maffeis.

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Maffeis, V., Cappellesso, R., Galuppini, F. et al. Tumor budding is an adverse prognostic marker in intestinal-type sinonasal adenocarcinoma and seems to be unrelated to epithelial-mesenchymal transition. Virchows Arch 477, 241–248 (2020). https://doi.org/10.1007/s00428-020-02748-1

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