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Abstract
Introduction/Background Type I EC, aka, endometrial endometrioid carcinoma (EEC) is a typical endocrine-related disease, closely associated with both hormonal imbalance and obesity. It has definitive precancerous stages that develops step-by-step from DPE, SH, CH, and EAH to cancer. This progression provides us an excellent model to investigate the mechanisms of sexual hormones and adipocyte involvement in the carcinogenesis of EC.
Methodology A total of 1874 cases were enrolled, including 764 cases of healthy women, 145 cases diagnosed with disordered proliferative endometrium (DPE), 250 cases with simple hyperplasia (SH), 200 cases with complex hyperplasia (CH), 259 cases with endometrial atypical hyperplasia (EAH), 256 cases of EC. Profiles of BMI and sex hormone levels were analyzed and compared in different groups. Multiple linear regression analysis was done to control for the counfounding factor, age.
Results Estradiol elevation only took place in pre-cancerous stage. However, progesterone trend is a bit delayed, the significant difference totally vanished until the stage EEC G2, which stage is also a contraindication for conservative treatment with high potency progestins. Nuclear ER-a and membranous GPER also peaked at the phase of EAH and sharply decreased at G1, while continue to further decrease at G2 and G3. No significant difference was found for free estrogen level (FEI) in different groups compared with the control. BMI gradually increases and peaks at EEC (G1, G2), and this group of patients was the only group with both median and mean BMI >25 kg/m2, aka, overweight.
Conclusion Our hypothesis is cells attain cancerous properties under the stimulation of estrogen, and once cells gain carnogenic mutation, estrogen is no longer the primary engine for cancer progression.
This phenomenon can be explained as ‘Guider Effect Model’ which we made an analogy for E2 as a guider in theater, once the cells seated in the ‘cancer’, the guider just left immediately.
Disclosure Nothing to disclose.
The characteristics of endocrine profiles at each stage of the disease progression when holding age
IHC staining of ER-a and GPER at different stage of the disease
Cohort characteristics of study population
Multivariate Linear Regression Analysis of E2 level with disease progression when holding patient age constant