Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility

Lei Zhao, Liyan Xu, Amanda Hemmerich, N. Lynn Ferguson, Cynthia D. Guy, Shannon J. McCall, Diana M. Cardona, Maria Westerhoff, Rish K. Pai, Shu Yuan Xiao, Beiyu Liu, Cynthia L. Green, John Hart, Xuefeng Zhang

Research output: Contribution to journalArticlepeer-review


The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, and recognition of desmoplasia may be challenging based on morphology. In this study, we tested the expression pattern of microfibril-associated protein 5 (MFAP5), a promising immunohistochemical marker for desmoplasia, in benign gallbladders with desmoplasia-like reaction and gallbladders with invasive adenocarcinoma. We also evaluated the diagnostic utility of MFAP5 in challenging cases with an interobserver agreement study. The results showed that all benign cases retained intact/positive MFAP5 staining pattern in periglandular connective tissue, whereas 79.3% (23 out of 29) of cases of adenocarcinomas demonstrated diffuse and complete loss of MFAP5 staining in the tumor stroma. Interobserver agreement was improved by 2.66 times when images of MFAP5 immunohistochemistry were provided. In conclusion, MFAP5 expression is downregulated in the desmoplastic stroma of gallbladder adenocarcinoma and may provide a useful diagnostic marker in difficult cases.

Original languageEnglish (US)
Pages (from-to)427-434
Number of pages8
JournalVirchows Archiv
Issue number3
StatePublished - Mar 2021


  • Desmoplasia
  • Gallbladder adenocarcinoma
  • Invasion
  • MFAP5

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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