Optimization of immunophenotypic panel to differentiate upper from lower gastrointestinal adenocarcinomas: Analysis of new and traditional markers

Aastha Chauhan, Monica Sanchez-Avila, Juan Manivel, Susan Dachel, Wendy Larson, Brian Hanson, Amy Gravely, Hector Mesa

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1 Scopus citations


Adenocarcinomas of the esophagus (EAC), stomach [gastric adenocarcinoma (GAC)], and colorectal carcinoma (CRC) frequently show similar morphology because upper gastrointestinal tumors (GITs) usually evolve from pathologies involving intestinal metaplasia. Upper and lower GIT may also show overlapping immunophenotypes when using the traditional CK7, CK20, and CDX2 panel, which in patients presenting with metastatic disease of unknown origin may lead to misdirected diagnostic workup and/or therapy. We compared the phenotype of upper and lower GIT using an expanded immunohistochemical panel that included the traditional and newer gastrointestinal markers: SATB2, DcR3, MUC5AC, and MUC6. The panel was applied to resection specimens from 40 CRC, 40 GAC, and 40 EAC. A panel using SATB2, CK7, and CDX2 provided the best discriminating power for separating upper from lower GIT and was applied to 101 biopsies including 17 EAC, 17 GAC, 19 CRC, 18 pancreatic adenocarcinomas, 15 cholangiocarcinomas, and 15 lung adenocarcinomas. The phenotype CK7+/CDX2+/SATB2- was moderately sensitive and highly specific of upper GIT, the phenotype CK7-/CDX2+/SATB2+ was highly sensitive and specific for lower GIT, the phenotypes CK7+/CDX2-/SATB2- and CK7+/CDX2-/SATB2+ favored pancreatobiliary or lung primaries. Less frequent phenotypes showed substantial overlap. Although strong diffuse expression of SATB2 was characteristic of CRC, weak and/or focal expression was present in one third or more of upper gastrointestinal, cholangiocarcinomas, and lung adenocarcinomas. DcR3, MUC5AC, and MUC6 improved specificity, but showed poor sensitivity, suggesting they should be used as second tier markers.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalApplied Immunohistochemistry and Molecular Morphology
Issue number1
StatePublished - Jan 2021

Bibliographical note

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  • Differential diagnosis
  • Gastrointestinal
  • Immunohistochemistry
  • Immunophenotyping
  • Neoplasms

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article


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