Comparative Use of Napsin A and Glypican 3 to Distinguish Endometrial Clear Cell from Serous and Endometrioid Carcinomas

Int J Gynecol Cancer. 2018 Sep;28(7):1318-1324. doi: 10.1097/IGC.0000000000001303.

Abstract

Objective: Diagnosis of endometrial clear cell carcinomas is difficult owing to the low reproducibility of histological cell type in high-grade endometrial cancers. Recently, immunoreactivity for napsin A and glypican 3 has been reported in clear cell cancers. We sought to evaluate the use of napsin A and glypican 3 staining to distinguish clear cell carcinoma from other high-grade endometrial cancers.

Methods/materials: Twenty cases of pure and mixed endometrial clear cell carcinoma were extracted from the 2000-2014 archival material in the Departments of Obstetrics & Gynecology and Pathology at Montefiore Medical Center and compared to serous and grade 3 endometrioid controls. Representative sections were stained with monoclonal antibodies to napsin A and glypican 3. Immunostains were independently reviewed by 2 pathologists to assess frequency and pattern of staining. Charts were reviewed for clinicopathologic and treatment data.

Results: Granular cytoplasmic positivity for napsin A was observed in 70% of endometrial clear cell carcinomas; only 25% showed cytoplasmic or membranous glypican 3 positivity. No serous or high-grade endometrioid tumors stained for either marker. No cases of clear cell carcinoma that stained negative for napsin A stained positive for glypican 3. No difference in the immunohistochemical profile was found between pure and mixed clear cell carcinomas and between early- and advanced-stage clear cell carcinomas.

Conclusions: Napsin A is a more sensitive marker for endometrial clear cell carcinoma than glypican 3. In histologically ambiguous cases, napsin A and glypican 3 may help distinguish clear cell carcinoma from other high-grade histologies. Further investigation of endometrial clear cell carcinoma is needed to identify additional diagnostic tools for this rare histology. Correlation of a unique immunohistochemical profile and clinical outcomes is necessary.

Publication types

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

MeSH terms

  • Adenocarcinoma, Clear Cell / diagnosis
  • Adenocarcinoma, Clear Cell / metabolism*
  • Adenocarcinoma, Clear Cell / pathology
  • Aged
  • Aspartic Acid Endopeptidases / metabolism*
  • Carcinoma, Endometrioid / diagnosis
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / pathology
  • Cystadenocarcinoma, Serous / diagnosis
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / pathology
  • Cytoplasm / metabolism
  • Diagnosis, Differential
  • Female
  • Formaldehyde
  • Glypicans / metabolism*
  • Humans
  • Middle Aged
  • Paraffin Embedding
  • Tissue Fixation

Substances

  • GPC3 protein, human
  • Glypicans
  • Formaldehyde
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human