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

  • Original Article
  • Published:
Pathology & Oncology Research

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.

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Abbreviations

CI:

Confidence intervall

ESR:

Estrogen receptor

FIGO:

Fédération Internationale de Gynécologie Obstétrique (International Federation of Gynecology and Obstetrics)

H&E:

Hematoxylin-eosin

HR:

Hazard ratio

IQR:

Interquartile range

KLFs:

Krüppel-like factors

KLF5:

Krüppel-like factor 5

KLF9:

Krüppel-like factor 9

KLF11:

Krüppel-like factor 11

m-RNA:

Messenger RNA

PGR:

Progesterone receptor

REA:

Repressor of estrogen receptor activity

Real-Time PCR:

Real-time polymerase chain reaction

RNA:

Ribonucleic acid

TMA:

Tissue micro array.

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Acknowledgements

The authors would like to thank the whole staff who collaborated in the clinical practice and in the study, especially during data collection. We are particularly grateful to Matteo De Luca and Patrizia Savini for the technical support, and to Dr. Raluca I. Necula for the linguistic revision.

Contribution to Authorship

Substantial contributions to conception and design or data acquisition or to data analysis and interpretation (LV, APL, MO, SM, FuA, VR, JC, AFr, RJL, LM). Drafting the article or critically revising it for important intellectual content (LV, APL, MO, SM, FuA, VR, JC, AFr, RJL, LM). All authors have read and approved the final manuscript.

Financial Support

University of Udine and Ennergi Research.

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Authors and Affiliations

  1. Radiology Department, University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy

    Luigi Viola

  2. Clinic of Obstetrics and Gynecology, DAME, Academic Hospital of Udine, University of Udine, Piazzale Santa Maria della Misericordia, 15, 33100, Udine, Italy

    Ambrogio P Londero

  3. Ennergi Research (Non-Profit Organization), Lestizza, 33050, Italy

    Ambrogio P Londero & Serena Bertozzi

  4. Breast Unit, DAME, Academic Hospital of Udine, University of Udine, 33100, Udine, Italy

    Serena Bertozzi

  5. Institute of Pathology, DAME, Academic Hospital of Udine, University of Udine, Udine, 33100, Italy

    Maria Orsaria, Stefania Marzinotto, Fulvio Antoniazzi, Valentina Renda & Laura Mariuzzi

  6. Clinic of Surgery, Academic Hospital of Udine, University of Udine, 33100, Udine, Italy

    Jacqueline Cinel

  7. Clinic of Obstetrics and Gynecology, Christophorus-Kliniken, 48653, Coesfeld, Germany

    Arrigo Fruscalzo

  8. Clinic of Obstetrics and Gynecology, University Hospital of Münster, Albert-Schweitzer-Campus 1, Gebäude: A1, 48149, Münster, Germany

    Arrigo Fruscalzo & Ralph J Lellé

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  1. Luigi Viola
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  2. Ambrogio P Londero
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Corresponding author

Correspondence to Ambrogio P Londero.

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The authors state that they have no potential conflicts of interest relevant to this article. This study received no financial support.

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Condensation

In patients affected by endometrioid endometrial carcinoma, higher expression levels of KLF5 and KLF11 correlated with a poorer prognosis.

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Viola, L., Londero, A.P., Bertozzi, S. et al. Prognostic Role of Krüppel-Like Factors 5, 9, and 11 in Endometrial Endometrioid Cancer. Pathol. Oncol. Res. 26, 2265–2272 (2020). https://doi.org/10.1007/s12253-020-00817-z

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  • DOI: https://doi.org/10.1007/s12253-020-00817-z

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