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Peer-reviewed Lead author Corresponding author International journal
Sep 28, 2021

Clinicopathological and prognostic significance of immunophenotypic characterization of endocervical adenocarcinoma using CLDN18, CDH17, and PAX8 in association with HPV status.

Virchows Archiv : an international journal of pathology
  • Shiho Asaka
  • ,
  • Tomoyuki Nakajima
  • ,
  • Koichi Ida
  • ,
  • Ryoichi Asaka
  • ,
  • Chinatsu Kobayashi
  • ,
  • Masayuki Ito
  • ,
  • Tsutomu Miyamoto
  • ,
  • Takeshi Uehara
  • ,
  • Hiroyoshi Ota

Volume
480
Number
2
First page
269
Last page
280
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1007/s00428-021-03207-1
Publisher
Springer Science and Business Media {LLC}

In 2020, the WHO published a new system for classifying invasive endocervical adenocarcinoma based on histological features and high-risk human papillomavirus (HPV) infection. However, immunophenotypes of each histological subtype require further investigation. We immunohistochemically analyzed 66 invasive endocervical adenocarcinomas using three cell-lineage-specific markers: claudin 18 (CLDN18) for gastric, cadherin 17 (CDH17) for intestinal, and PAX8 for Müllerian epithelial cells. We identified five immunophenotypes of endocervical adenocarcinoma: gastric (21%); intestinal (14%); gastrointestinal (11%); Müllerian (35%); and not otherwise specified (NOS) (20%). Adenocarcinomas with gastric immunophenotype, characterized by aging (p = 0.0050), infrequent HPV infection (p < 0.0001), concurrent lobular endocervical glandular hyperplasia (p = 0.0060), lymphovascular invasion (p = 0.0073), advanced clinical stage (p = 0.0001), and the poorest progression-free (p < 0.0001) and overall (p = 0.0023) survivals, were morphologically compatible with gastric-type adenocarcinoma of the WHO 2020 classification. Conversely, most adenocarcinomas with Müllerian (91%) and intestinal (89%) immunophenotypes were HPV associated and morphologically compatible with usual- or intestinal-type adenocarcinomas of the WHO 2020 classification. The morphology of adenocarcinomas with gastrointestinal immunophenotype was intermediate or mixed between those of gastric and intestinal immunophenotypes; 57% were HPV associated. Adenocarcinomas with NOS immunophenotype were mainly HPV associated (85%) and histologically poorly differentiated. Multivariate analysis revealed that gastric (p = 0.008), intestinal + gastrointestinal (p = 0.0103), and NOS (p = 0.009) immunophenotypes were independent predictors of progression-free survival. Immunophenotypes characterized by CLDN18, CDH17, and PAX8 exhibited clinicopathological relevance and may improve the diagnostic accuracy and prognostic value of conventional histological classification.

Link information
DOI
https://doi.org/10.1007/s00428-021-03207-1
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34581850
ID information
  • DOI : 10.1007/s00428-021-03207-1
  • ORCID - Put Code : 100652761
  • Pubmed ID : 34581850

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