Bmi-1 Immunohistochemical Expression in Endometrial Carcinoma is Correlated with Prognostic Activity

Medicina (Kaunas). 2020 Feb 12;56(2):72. doi: 10.3390/medicina56020072.

Abstract

Background and objectives: B-lymphoma Mo-MLV insertion region 1 (Bmi-1) is a stem cell factor that is overexpressed in various human cancer tissues. It has been implicated in cancer cell proliferation, cell invasion, distant metastasis, and chemosensitivity, and is associated with patient survival. Several reports have also identified Bmi-1 protein overexpression in endometrial carcinoma; however, the relationship between Bmi-1 expression and its significance as a clinicopathological parameter is still insufficiently understood. Accordingly, the present study aimed to clarify whether immunohistochemical staining for Bmi-1 in human endometrial carcinoma and normal endometrial tissues can be used as a prognostic and cell proliferation marker. Materials and Methods: Bmi-1 expression was assessed in endometrioid carcinoma (grade 1-3) and normal endometrial tissues (in the proliferative and secretory phases) by immunohistochemistry; protein expression was evaluated using the nuclear labeling index (%) in the hot spot. Furthermore, we examined other independent prognostic and proliferation markers, including the protein levels of Ki-67, p53, and cyclin A utilizing semi-serial sections of endometrial carcinoma tissues. Results: The expression of the Bmi-1 protein was significantly higher in all grades of endometrial carcinoma than in the secretory phase of normal tissues. Moreover, Bmi-1 levels tended to be higher in G2 and G3 tissues than in G1 tissue, without reaching significance. Bmi-1 expression showed no notable differences among International Federation of Gynecology and Obstetrics (FIGO) stages in endometrial carcinoma. Furthermore, we observed a significant positive relationship between Bmi-1 and Ki-67, cyclin A, or p53 by Spearman's rank correlation test, implying that high Bmi-1 expression can be an independent prognostic marker in endometrial carcinoma. Conclusions: Our study suggests that Bmi-1 levels in endometrial carcinoma tissues may be useful as a reliable proliferation and prognostic biomarker. Recently, the promise of anti-Bmi-1 strategies for the treatment of endometrial carcinoma has been detected. Our results provide fundamental data regarding this anti-Bmi-1 strategy.

Keywords: Bmi-1; biomarker; endometrial carcinoma; immunohistochemical staining.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Biopsy / methods
  • Cyclin A / analysis
  • Early Detection of Cancer / methods
  • Endometrial Neoplasms / diagnosis*
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Immunohistochemistry / standards*
  • Immunohistochemistry / statistics & numerical data
  • Japan
  • Ki-67 Antigen / analysis
  • Middle Aged
  • Polycomb Repressive Complex 1 / analysis*
  • Polycomb Repressive Complex 1 / blood
  • Predictive Value of Tests*
  • Tumor Suppressor Protein p53 / analysis

Substances

  • BMI1 protein, human
  • Biomarkers, Tumor
  • Cyclin A
  • Ki-67 Antigen
  • MKI67 protein, human
  • Tumor Suppressor Protein p53
  • Polycomb Repressive Complex 1