6.6. Regulation of endometrial homeostasis
It is generally acknowledged that dysfunction of apoptosis is an important factor in carcinogenesis (Williams 1991). The endometrium is a highly active tissue, which undergoes regular periods of cell proliferation and cell death. Apoptosis was observed to participate in the physiological regulation of the endometrium during normal menstrual cycles (IV). Endometrial hyperplasias are thought to result from increased cellular proliferation driven by an unopposed estrogen influence (Kounelis et al. 2000). The rate of apoptosis was similar in endometrial hyperplasia to that in normal cellular proliferation (V), suggesting that hyperplasia is indeed triggered by escalated proliferation, rather than diminished cell death. However, it is possible that abnormalities in the apoptosis-regulating pathways partially contribute to the development of hyperplasia, due to inability of cell death mechanisms to respond to the increased proliferation. Grade I endometrial cancer exhibited a lower rate of apoptosis than seen in normal endometrium or endometrial hyperplasias, suggesting that the onset of cancer might be related to a low rate of apoptosis (V). However, apoptosis was significantly increased in grade II carcinomas. This finding is in agreement with previous reports that have described a high rate of apoptosis in malignant tumours (Aihara et al. 1995, Törmänen et al. 1995). In grade III carcinoma, the rate of apoptosis was significantly decreased from that in grade II, possibly indicating lost control of cell homeostasis, poor differentiation and increased malignancy.
Bcl-2 and Bax expression were also detected in both endometrial hyperplasia and carcinoma. Both proteins were present in hyperplasias, but Bcl-2 was downregulated in grade II carcinoma, while weak Bax expression was detected in grade II and III carcinomas. A decrease in the Bcl-2/Bax ratio might also predispose cells to apoptosis in endometrial cancer, similarly to normal cyclic endometrium.
