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

Virchows Arch. 2021 Mar;478(3):427-434. doi: 10.1007/s00428-020-02925-2. Epub 2020 Sep 7.


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.

Keywords: Desmoplasia; Gallbladder adenocarcinoma; Invasion; MFAP5.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Case-Control Studies
  • Contractile Proteins / analysis*
  • Databases, Factual
  • Down-Regulation
  • Female
  • Gallbladder Neoplasms / chemistry*
  • Gallbladder Neoplasms / pathology
  • Humans
  • Immunohistochemistry*
  • Intercellular Signaling Peptides and Proteins / analysis*
  • Male
  • Middle Aged
  • Observer Variation
  • Predictive Value of Tests
  • Reproducibility of Results
  • Stromal Cells / chemistry*
  • Stromal Cells / pathology
  • United States


  • Biomarkers, Tumor
  • Contractile Proteins
  • Intercellular Signaling Peptides and Proteins
  • MFAP5 protein, human