Differential Expressions of Ki-67, Bcl-2, and Apoptosis Index in Endometrial Cells of Women With and Without Type II Diabetes Mellitus and Their Correlation with Clinicopathological Variables

Abstract

The objective of this study was to investigate proliferation, apoptosis, and antiapoptotic molecule expression in endometrial cells of reproductive-aged women with and without type II diabetes mellitus (T2D). In this case-control study, a total of 80 endometrial tissue specimens from reproductive-aged women (35 in the proliferative phase and 45 in the secretory phase) were examined. The age and body mass index (BMI) were matched between the groups. Formalin-fixed and paraffin-embedded endometrial tissue samples were used for immunohistochemistry analysis. The presence of proliferation was evaluated with Ki-67 expression, antiapoptotic function of cells was evaluated with Bcl-2 expression, and apoptosis was evaluated with terminal deoxynucleotidyl transferase (TUNEL) immunoreactivity in both the glandular epithelium and stroma of endometrial tissue samples from women with and without T2D. Ki-67 expression in the glandular epithelium and Bcl-2 expression in both the glandular epithelium and stroma were significantly higher in endometrial tissue samples of women in the T2D group than the control group (p = 0.0008, p = 0.0022, and p = 0.0261, respectively). TUNEL immunoreactivity was significantly lower in the glandular epithelium of women in the T2D group than the control group (p = 0.0001). Glandular Ki-67 expression correlated positively with BMI, use of insulin, and hemoglobin A1c level (p = 0.0034, p = 0.0154, and p = 0.0011, respectively). Glandular Bcl-2 expression correlated positively with BMI and duration of T2D (p = 0.0090 and p = 0.0109, respectively). Stromal Bcl-2 expression correlated positively with duration of T2D (p = 0.0069). TUNEL immunoreactivity in the glandular epithelium correlated negatively with duration of T2D (p = 0.0340) and positively with the use of oral antidiabetic agents (p = 0.0226). Compared to age and BMI-matched controls, women with T2D experienced increased cell proliferation and decreased apoptosis in the glandular epithelium and increased antiapoptotic function in both the glandular epithelium and stromal cells. High BMI values in women with diabetes seemed to contribute to increased cell proliferation and increased antiapoptotic function in the glandular epithelium but not the stromal cells.