Indices of cell proliferation and PTEN expression in benign, premalignant, and malignant endometrial lesions

The objective of this study was the evaluation of cell proliferation and PTEN expression in simple endometrial hyperplasia (SH), hyperplasia with atypia (HA), and carcinoma (CA) tissue samples by the use of immunohistochemistry. Surgically obtained endometrial samples were grouped according to the histopathologically confirmed diagnosis: SH (n=3), HA (n=8), and CA (n=8). Immunohistochemical reactions were performed using anti-Ki-67 and anti-PTEN antibodies. Ki-67-positive glandular cells were counted in all fields of view (FOV) for each region of interest using x400 magnification. PTEN expression was scored as a weak, medium, or strong if <10, 10-50, and >50% of cells respectively were positive. Stromal expression of proliferation marker (PM) and PTEN was estimated as prominent if >50% of cells in FOV were positive. The mean percentage of Ki-67-positive glandular cells was higher in CA – 35.7% (SD=5.7) with a range from 33.9 up to 37.4% vs. 26.7% (SD=13.5) in HA and 11.05% (SD=16.2) – in SH. Differences between all three groups were statistically significant (p=0.000). Prominent expression of PM in stromal cells was less frequent in the case of CA (51.4%) when compared to HA (64.7%) and SH (65.8%). Expression of Ki-67 in glandular cells was inversely proportional to stromal tissue component (p=0.000). Weak PTEN expression was more prevalent in CA (25.6%) vs. HA (16.7%) and SH (4.6%). By contrast, strong PTEN expression demonstrated higher rates in SH (52.6%) when compared to HA (37.4%) and CA (29.4%). Stromal expression was significantly more prominent in the SH group (83.6%) vs. HA (61.5%) and CA (44.7%). The study results suggest expression of the Ki-67 marker increases with cell atypia, with the opposite tendency in the tissue stromal component. The decline of PTEN expression along the axis SH-CA reaffirms the crucial role of PTEN gene inactivation in malignant endometrial transformation.