Calponin and MUC6 complement inhibin as diagnostic immunomarkers of serous cystadenoma in endoscopic ultrasound-guided aspiration/biopsy specimens

Histopathology. 2021 Aug;79(2):252-259. doi: 10.1111/his.14362. Epub 2021 May 12.

Abstract

Aims: Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET.

Methods and results: Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6.

Conclusions: Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens.

Keywords: immunohistochemistry; pancreas; sensitivity; serous cystadenoma; specificity.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism*
  • Calponins
  • Cohort Studies
  • Cystadenoma, Serous / diagnosis*
  • Cystadenoma, Serous / immunology*
  • Cystadenoma, Serous / pathology
  • Duodenum / pathology
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration* / instrumentation
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Immunohistochemistry
  • Inhibins / immunology
  • Inhibins / metabolism*
  • Male
  • Microfilament Proteins / immunology
  • Microfilament Proteins / metabolism*
  • Middle Aged
  • Mucin-6 / metabolism*
  • Neuroendocrine Tumors / pathology
  • Pancreas / pathology
  • Stomach / pathology
  • Synaptophysin / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Glucose Transporter Type 1
  • MUC6 protein, human
  • Microfilament Proteins
  • Mucin-6
  • Synaptophysin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Inhibins