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Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values

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Pathology & Oncology Research

Abstract

Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p < 0.001), differentiation grade 3 (p < 0.001), serrated adenocarcinoma subtype (p < 0.001), serrated (p < 0.001), medullary (p = 0.005), and mucinous component (p = 0.004), cytoplasmic eosinophilia (p < 0.001), discernible nuclei (p = 0.001), preserved polarity (p < 0.001), lymphatic invasion (p = 0.01), BRAFV600E mutation (p < 0.001), MSI-H status (p < 0.001) and CIMP-H status (p = 0.019). Multivariate analyses revealed that mucinous component (p = 0.002), lymphatic invasion (p = 0.02) and BRAFV600E mutation (p < 0.001) were independently associated with AnnexinA10 expression. In addition, AnnexinA10 was an indicator of poorer overall survival (OS) in UICC stage IV adenocarcinomas (p = 0.01) only. Gremlin1 expression was neither associated with serrated adenocarcinoma subtype (p = 0.51) nor with AnnexinA10 expression (p = 0,31), but was significantly associated, in univariate analysis with male gender (p = 0.002), younger age (p = 0.002), left tumor location (p = 0.04), and MSS status (p = 0.03). Gremlin1 expression was associated with better OS only in UICC stage III colon adenocarcinomas (p = 0.006). Colon adenocarcinomas expressing AnnexinA10 have distinct clinico-pathological and molecular features. AnnexinA10 expression is an indicator of poorer OS in UICC stage IV patients. Gremlin1 expression is not associated with serrated adenocarcinomas subtype. Its expression was associated with better OS in UICC Stage III patients.

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Authors’ Contribution to the Study

Conceptualization: M-DD; CB-R.

Data curation: BMA; CB.

Formal analysis: BMA; AMB; CB.

Funding acquisition: CB-R.

Investigation: BMA; AMB; CF; NB; CB-R.

Methodology: CB.

Project administration: M-DD; CB-R.

Software: CB.

Supervision: OB; M-DD; CB-R.

Validation: OB; RK; M-DD.

Visualization: OB; RK; M-DD.

Roles/Writing - original draft: BMA, CB-R.

Writing - review &editing: CB; OB; RK; AMB; M-DD.

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Benjamin Marquet, Aude Marchal Bressenot, Caroline Fichel, Nicole Bouland, Coralie Barbe, Marie-Danièle Diebold and Camille Boulagnon-Rombi. The first draft of the manuscript was written by Benjamin Marquet and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported by le Centre Hopsitalier Universitaire de Reims, Reims, France [grant numbers AOL 2015–11, 2015].

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Authors and Affiliations

  1. Department of Biopathology, Academic Hospital, rue du Général Koenig, 51100, Reims, France

    Benjamin Marquet, Aude Marchal Bressenot, Marie-Danièle Diebold & Camille Boulagnon-Rombi

  2. Department of Pathology, Medicine University, Reims, France

    Benjamin Marquet, Aude Marchal Bressenot, Caroline Fichel, Nicole Bouland, Marie-Danièle Diebold & Camille Boulagnon-Rombi

  3. Clinical Research Unit, Academic Hospital, Reims, France

    Coralie Barbe

  4. Gatroenterology and Digestive Oncology Department, Academic Hospital, Reims, France

    Olivier Bouché

  5. Digestive Surgery Department, Academic hospital, Reims, France

    Reza Kianmanesh

  6. UMR CNRS/URCA 7369 MEDyC, Medicine University, Reims, France

    Camille Boulagnon-Rombi

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  1. Benjamin Marquet
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Correspondence to Benjamin Marquet.

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The study was performed in accordance with the ethical standards. All patients had given their consent for biospecimen use and the study was performed in accordance with the ethical standards laid down in the Declaration of Helsinki. The written consent of patients to the biospecimen use was obtained in all cases. Approval for the study was previously obtained from the local Institutional Review Board and the Tissue Bank Management Board.

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Marquet, B., Marchal Bressenot, A., Fichel, C. et al. Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values. Pathol. Oncol. Res. 26, 2509–2521 (2020). https://doi.org/10.1007/s12253-020-00857-5

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