Small bowel adenocarcinomas featuring special at-rich sequence-binding protein 2 (Satb2) expression and a colorectal cancer-like immunophenotype: A potential diagnostic pitfall

Giuseppe Neri, Giovanni Arpa, Camilla Guerini, Federica Grillo, Marco Vincenzo Lenti, Paolo Giuffrida, Daniela Furlan, Fausto Sessa, Erica Quaquarini, Alessandra Viglio, Cristina Ubezio, Alessandra Pasini, Stefano Ferrero, Gianluca Sampietro, Sandro Ardizzone, Giovanni Latella, Claudia Mescoli, Massimo Rugge, Fabiana Zingone, Valeria BarresiRachele Ciccocioppo, Paolo Pedrazzoli, Gino Roberto Corazza, Ombretta Luinetti, Enrico Solcia, Marco Paulli, Antonio Di Sabatino, Alessandro Vanoli

Research output: Contribution to journalArticlepeer-review

Abstract

Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn’s disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7−/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7−/CK20-SBAs were enriched with MMR-deficient cases (71%) and patients with CK7−/CK20− or CK7−/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20− or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7−/CK20− cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.

Original languageEnglish
Article number3441
Pages (from-to)1-14
Number of pages14
JournalCancers
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Celiac disease
  • Crohn’s disease
  • Cytokeratin
  • Mismatch repair
  • Small intestine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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