Our study showed no significant difference in Bcl-2 and Ki67 expression in the endometrial polyps of obese and non-obese patients, except in polyps greater than 2cm, with overexpression of Bcl-2 in stroma.
Doubt persists regarding the origin of endometrial polyps. The polyps were thought to originate in an area with intense proliferation of endometrial basal cells. Vinatier et al. (1996) postulated that the epithelial cells of the endometrial basal layer did not undergo apoptosis due to Bcl-2 overexpression.9
Inceboz US et al. (2006) found Bcl-2 overexpression in the glandular compartment of polyps in both pre- and postmenopausal obese women, suggesting that apoptosis blockage is more important than the proliferative action of Ki67.10
Arends (1999) verified overexpression of Bcl-2, which has anti-apoptotic functions, in the endometrial basal layer throughout the menstrual cycle. This finding explains the renewal capacity of the endometrium after menstruation, which allows basal cells to remain intact.11
Mittal et al. (1996) suggest that oestrogen receptor (OER) overexpression and PR underexpression are possible causes of the formation of endometrial polyps.12 Taylor (2003) also found a significant increase in OER in polyps in the secretory phase of the menstrual cycle. Under normal conditions, OER synthesis is inhibited by the activity of circulating progesterone during this phase of the menstrual cycle.5
Taylor (2003) analysed the Bcl-2 and Ki67 expression in polyps during both the proliferative and secretory phases of the menstrual cycle. The researchers found Bcl-2 overexpression in the gland and stroma compared to the surrounding endometrium during the proliferative phase. There was no difference in Ki67 expression at this stage of the cycle. During the secretory phase, there was no difference in expression of these genes relative to that in the surrounding endometrium.5
Gompel et al. (1994) found Bcl-2 and Ki67 overexpression in the glandular tissue of polyps in the proliferative phase. In the secretory phase, Ki67 expression was higher but still lower than the level observed in the proliferative phase. According to these authors, both Bcl-2 and Ki67 play a role in the formation of polyps.13
In postmenopausal women, however, Pinheiro (2014) found PR overexpression in both the gland and stroma of endometrial polyps in obese patients.6 Gul (2010) found PR overexpression in the stroma of polyps, with high circulating oestrogen levels.14 The same findings were reported by Belisario (2006).15
The hyperoestrogenism of obese menopause women explains these findings. Siiteri's (1973) showed peripheral conversion of androgen to oestrogen in adipose tissue (aromatase activity). This activity is stronger in obesity, especially after menopause. At this stage of life, there is no opposite progesterone for oestrogenic activity, thus explaining its possible role in the origin of polyps and the PR overexpression secondary to oestrogenic activity.16 Oguz (2005) agree with this hypothesis.17
We did not find Bcl-2 overexpression in polyps of obese postmenopausal patients, except in polyps greater than 2cm, and in stroma. It is possible that the small number of patients in our sample affected the result. The inclusion of more patients may have produced results similar to those of the authors mentioned above.
Pinheiro et al. (2014) found higher Bcl-2 expression in the glandular tissue of the polyps of obese postmenopausal patients than in non-obese patients (p<0.0001). In the stroma, however, there was no significant difference in Bcl-2 expression (p=0.1975). Regarding Ki67 expression, the authors found no difference between obese and non-obese postmenopausal patients.6
Villavicencio et al. (2010) found 9.9-fold higher Ki67 expression on endometria in obese patients compared to non-obese patients. Obese patients showed up to 12.6-fold higher proliferation than the normal-weight group.18
As we known, Bcl-2 is an oncogene involved in apoptosis and its loss of expression was related to more aggressive endometrial cancer (higher grade, advanced stage and lymph node invasion). Stanescu et al., (2014) didn´t find a correlation between expression of bcl-2 and grade or stage of the endometrial cancer.19
Troncon et al., (2017) evaluate the expression of genetic markers in endometrial polyps of patients with and without postmenopausal bleeding (Bcl-2 and others). The authors didn´t found statistical differences between the two groups concerning the expression of the studied endometrial cancer risk factor genes, or with regard to the clinical aspects evaluated.20
We didn´t find overexpression of Bcl-2 or Ki67 in the polyps of obese postmenopausal patients. The results, however, were not what we expected. The same findings were published by the cited authors, in part or in full.
There is no significant difference in Bcl-2 and Ki67 expression in the endometrial polyps of obese and non-obese patients in menopause. Questions still exist regarding both the formation and treatment of endometrial polyps. Which patients should be monitored and which should be subjected to the systematic excision of these polyps due to the risk of malignancy? Further studies are needed to better answer these questions.