Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells

Cytopathology. 2019 Mar;30(2):201-208. doi: 10.1111/cyt.12653. Epub 2018 Dec 18.


Background: Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples.

Results: In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens.

Conclusions: Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.

Keywords: SMAD4; cell block; endoscopic ultrasound-guided fine needle aspiration; immunohistochemistry; pancreatic cancer.

MeSH terms

  • Aged
  • Cytodiagnosis*
  • Diagnosis, Differential
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Smad4 Protein / genetics
  • Smad4 Protein / isolation & purification*
  • Specimen Handling


  • SMAD4 protein, human
  • Smad4 Protein