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HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example

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Abstract

Signet-ring cell carcinoma (SRCC) developing in the colorectum (CR) is infrequently identified at an early stage (no deeper than submucosa). Most such examples involve the submucosa. Merely 13 cases of intramucosal CR SRCC are at hand. We recently had the opportunity to study a specimen with two synchronous early-stage SRCC, developed in a 65-year-old hereditary nonpolyposis colorectal cancer male patient with a known disease-causing mutation in MLH1. A right hemicolectomy specimen comprised a 15-mm intramucosal cecal lesion, featuring zones of conventional tubular adenoma and intraepithelial SRCC as well as tumor cells multifocally permeating the lamina propria and a 12-mm submucosally expanding SRCC of the ascending colon. The intramucosal and intraepithelial as well as stromal lesional cells displayed a normal membranous expression of β-catenin and E-cadherin; submucosally infiltrating cells featured alterations in this complex with loss of membranous expression of both proteins and a shift with nuclear accumulation of β-catenin, suggesting a disruption of the Wingless signaling pathway taking place at the transition from the intramucosal to the submucosal level.

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Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, HNPCC-register, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Louise Klarskov & Susanne Holck

  2. Department of Gastroenterology, HNPCC-register, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Inge Bernstein

Authors
  1. Louise Klarskov
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  2. Inge Bernstein
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  3. Susanne Holck
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Correspondence to Susanne Holck.

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Part of this study has been previously presented at the annual meeting of the Danish Society of Pathological Anatomy and Cytology, 2008.

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Klarskov, L., Bernstein, I. & Holck, S. HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example. Virchows Arch 454, 115–124 (2009). https://doi.org/10.1007/s00428-008-0691-9

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  • DOI: https://doi.org/10.1007/s00428-008-0691-9

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