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Frequent loss of claudin-4 expression in dedifferentiated and undifferentiated endometrial carcinomas

Basile Tessier-Cloutier1, Robert A Soslow2, Colin J R Stewart3

  • 1Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.

Histopathology
|April 20, 2018
PubMed
Abstract

Insights

Claudin-4 is typically absent in the undifferentiated parts of aggressive endometrial cancers (UECs/DDECs), even those with epithelial origins. This loss of claudin-4 supports their undifferentiated nature.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Genitourinary Pathology

Background:

  • Dedifferentiated endometrial carcinomas (DDECs) and undifferentiated endometrial carcinomas (UECs) are aggressive cancers often linked to SWI/SNF complex gene mutations.
  • Claudin-4, a protein involved in cell junctions, has shown varied expression in SWI/SNF-deficient tumors.

Purpose of the Study:

  • To investigate claudin-4 expression patterns in UECs/DDECs and other high-grade uterine carcinomas.
  • To determine if claudin-4 expression can differentiate tumor origins in endometrial cancers.

Main Methods:

  • Immunohistochemistry was used to analyze claudin-4 expression in a cohort of 44 UECs/DDECs, 50 carcinosarcomas, 164 grade 3 endometrioid carcinomas, 57 serous carcinomas, and 20 clear cell carcinomas.
  • Tumors with less than 5% claudin-4 staining were classified as negative.

Main Results:

  • Nearly all UECs/DDECs, regardless of SWI/SNF status, lacked claudin-4 in their undifferentiated components.
  • Differentiated components of DDECs consistently expressed claudin-4.
  • Claudin-4 was absent in the sarcomatous part of carcinosarcomas and in 24% of grade 3 endometrioid and serous carcinomas.

Conclusions:

  • Claudin-4 expression is often lost or reduced in high-grade endometrial carcinomas, particularly in the undifferentiated areas of SWI/SNF-deficient UECs/DDECs.
  • Claudin-4 expression is not a reliable marker for distinguishing epithelial versus mesenchymal origins in endometrial tumors.
  • The downregulation of claudin-4 in SWI/SNF-deficient UECs/DDECs reinforces their classification as undifferentiated malignancies.
Keywords:
SWI/SNF proteinsclaudin-4endometrial cancerendometrioid adenocarcinomaundifferentiated carcinomauterine sarcomas

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