Clinicopathological Significance of Claudin-6 Immunoreactivity in Low-grade, Early-stage Endometrioid Endometrial Carcinoma

In Vivo. 2025 Jan-Feb;39(1):367-374. doi: 10.21873/invivo.13837.

Abstract

Background/aim: Dysregulation of claudin 6 (CLDN6) expression has been widely documented in various malignancies. CLDN6 is aberrantly expressed in many types of human carcinomas; however, its clinical significance in endometrial carcinoma has seldom been investigated. This study aimed to examine the immunohistochemical expression status of CLDN6 in low-grade, early-stage endometrioid endometrial carcinoma (LGES-EEC) and to assess its clinicopathological significance.

Materials and methods: We performed immunostaining for CLDN6 in 118 tissue samples from LGES-EECs. Protein expression levels were interpreted using a semi-quantitative histoscore method. All statistical analyses were performed.

Results: CLDN6 was primarily localized along the membranes of the tumor cells. We considered histoscore ≥10 (the staining proportion ≥5% and intensity ≥2) as positive immunoreactivity for CLDN6. Twenty-six of the 118 patients (22.0%) showed CLDN6 positivity. Positive CLDN6 expression was significantly associated with deeper myometrial invasion (p=0.001), higher initial stage (p=0.015), and substantial lymphovascular space invasion (p=0.018).

Conclusion: Aberrant CLDN6 expression is involved in tumor progression in LGES-EECs. In addition, targeting CLDN6 may offer clinical utility in patients with endometrial carcinoma.

Keywords: Endometrium; claudin-6; early stage; endometrioid carcinoma; immunohistochemistry; low grade.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / metabolism
  • Carcinoma, Endometrioid* / genetics
  • Carcinoma, Endometrioid* / metabolism
  • Carcinoma, Endometrioid* / pathology
  • Claudins* / genetics
  • Claudins* / metabolism
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / pathology
  • Female
  • Humans
  • Immunohistochemistry*
  • Middle Aged
  • Neoplasm Grading*
  • Neoplasm Staging*
  • Prognosis

Substances

  • claudin 6
  • Claudins
  • Biomarkers, Tumor