Prognostic Role of Krüppel-Like Factors 5, 9, and 11 in Endometrial Endometrioid Cancer

Pathol Oncol Res. 2020 Oct;26(4):2265-2272. doi: 10.1007/s12253-020-00817-z. Epub 2020 May 25.

Abstract

Background and objective: Krüppel-like factors (KLFs) are transcription factors with the ability to mediate cross-talk with signaling pathways involved in cell proliferation control, apoptosis, migration, and differentiation. They also appear to influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Our study aims to evaluate the potential prognostic role of KLF5, KLF9, and KLF11 in endometrial cancer, and their correlation with hormonal receptor status and cellular proliferation.

Materials and methods: Retrospective observational study on cases of endometrioid endometrial adenocarcinoma collected in the period January 2000-December 2011 at the University of Udine. Formalin-fixed, paraffin-embedded tissue samples were all submitted to tissue microarray immunohistochemical study. A survival analysis was performed.

Results: One hundred forty seven patients were included in the study with a mean age at surgery of 65.6 years (±10.2). 80.3% of endometrial malignancies were classified as stage FIGO I (118/147). Radiation therapy and chemotherapy were administered in 62.3% (91/146) and 6.2% (9/145) of patients respectively. Five-year overall survival and disease-free survival resulted 85.4% (95% CI, 79.8-91.4%) and 79.4% (95% CI, 73.0-86.4%) respectively. A high Ki-67, cytoplasmatic KLF5 (HR 4.72, CI.95 1.61-13.89, p < 0.05), and nuclear KLF11 (HR 3.04, CI.95 0.99-9.36, p = 0.053) scores correlated with a shorter overall survival. In addition, a high nuclear KLF11 (HR 2.59, CI.95 1.13-5.95, p < 0.05) score correlated with a shorter disease-free survival.

Conclusions: In patients affected by endometrioid endometrial carcinoma, higher staining levels of KLF5 and KLF11 correlated with a poorer prognosis. However, further studies are required in order to better clarify the role of KLFs in the natural history of endometrial cancer.

Keywords: Endometrial cancer; Endometrioid endometrial cancer; KLF; KLF11; KLF5; KLF9; Krüppel-like factors.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology*
  • Carcinoma, Endometrioid / surgery
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Endometrial Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Prognosis
  • Repressor Proteins / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • KLF11 protein, human
  • KLF5 protein, human
  • KLF9 protein, human
  • Kruppel-Like Transcription Factors
  • Repressor Proteins