Immunocytochemistry for MUC4 and MUC16 is a useful adjunct in the diagnosis of pancreatic adenocarcinoma on fine-needle aspiration cytology

Arch Pathol Lab Med. 2013 Apr;137(4):546-51. doi: 10.5858/arpa.2011-0229-OA.

Abstract

Context: Diagnoses rendered as atypical/suspicious for malignancy on fine-needle aspiration (FNA) of pancreatic mass lesions range from 2% to 29% in various studies. We have identified the expression of 3 genes, MUC4, MUC16, and NGAL that are highly upregulated in pancreatic adenocarcinoma. In this study, we analyzed the expression of these markers in FNA samples to determine whether they could improve sensitivity and specificity.

Objective: To evaluate the utility of MUC4, MUC16, and NGAL in the evaluation of pancreatic FNA specimens.

Design: Records of pancreatic FNAs performed during 10 consecutive years were reviewed. Unstained sections from corresponding cell blocks were immunostained for MUC4, MUC16, and NGAL (polyclonal). Immunostaining was assessed using the H-score (range, 0-3). Any case with an H-score of >0.5 was considered positive.

Results: Cases were classified using cytomorphologic criteria as adenocarcinoma (31 of 64; 48.4%), benign (17 of 64; 26.6%), and atypical/suspicious (16 of 64; 25%). On follow-up, all cases (100%; 31 of 31) diagnosed as carcinoma on cytology were confirmed on biopsy/resection samples or by clinical follow-up (such as unresectable disease). Of the cases diagnosed as atypical/suspicious, 69% (11 of 16) were found to be positive for adenocarcinoma and 31% (5 of 16) were benign on subsequent follow-up. Overall sensitivity and specificity, respectively, for the various markers for the detection of pancreatic adenocarcinoma were as follows: MUC4 (74% and 100%), MUC16 (62.9% and 100%), and NGAL (61.3% and 58.8%). In cases that were atypical/suspicious on cytology, expression of MUC4 and MUC16 was 100% specific for carcinoma with sensitivities of 63.6% and 66.7%, respectively.

Conclusion: Immunocytochemistry for MUC4 and MUC16 appears to be a useful adjunct in the classification of pancreatic FNA samples, especially in cases that are equivocal (atypical/suspicious) for adenocarcinoma on cytomorphologic assessment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Biomarkers, Tumor / metabolism
  • Biopsy, Fine-Needle
  • CA-125 Antigen / metabolism*
  • Cytodiagnosis / methods*
  • Humans
  • Immunohistochemistry / methods*
  • Membrane Proteins / metabolism*
  • Mucin-4 / metabolism*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CA-125 Antigen
  • MUC16 protein, human
  • MUC4 protein, human
  • Membrane Proteins
  • Mucin-4