The Association Between Urine Estradiol, 2-methoxyestradiol And Endometrial Cancer

Objective: It is found in long-term clinicai and experimental study that persistent estrogen exposure without progesterone against is an important factor in the pathogenesis of endometrial cancer. Estradiol (E₂) is female sex hormone with the strongest biological activity, and is valueble for diagnosis and discriminate some endocrine and gynecological diseases. With the deeper research to the estrogen, it is gradually discovered that estrogen metabolites have a closer relationship with the occurrence and development of tumor. Some estrogen metabolites are carcinogenic, while some others are antitumor. 2-methoxyestradiol(2MOE₂)is generally considered to have the property of control the growth of tumor, by inducing apoptosis, inhibiting the angiogenesis, and disturbing cell cycle. In the study, the aim is to examine the level of E₂ and 2MOE₂ in the urine, with endometrial cancer patients as case population, healthy women as control population.Methods: Based on the case- control study, the 24 hours urine were collected from 32 cases and 32 controls. The concentration of 2MOE₂ was detected by hollow fiber liquid phase micro-extraction and high performance liquid chromatogram mass spectrography(HPLC-MS). While the concentration of E₂ was detected by the euzymelinked immunosorbent assay (ELISA). Then to compare the total quantity of 2MOE₂ and E₂ according to urine volum of 24 hours.Statistical analysis was performed using SPSS13.0 software package. P<0.05 was considered significant. The normality of 2MOE₂ and E₂ expression level was analyzed by the test of normality. The results of experiment were expressed as median, and then were changed into the form of LOG₁₀, expressed as x±s. Comparison of two groups was performed by the t-test and three groups by the One-Way ANOVA. Results:1 The distributions of E₂ and 2MOE₂ concentrations were unnormal. The median of E₂ in the case group was 2.82 ng/ml, while in the control group was2.34 ng/ml. The expression of 2MOE₂ in the case group was 4.20 pg/ml, while in the control group was 9.08 pg/ml. 2 The distributions of the quantity of 24 hours of E₂ and 2MOE₂ were unnormal. The median of 24 hours of E₂ quantity in the case group was 4.54 mg, while in the control group was 2.83 mg. The median of 2MOE₂ in the case group was 7.32 ng, while in the control group was 11.73 ng.3 The quantities of 24 hours E₂ and 2MOE₂ were changed into LOG₁₀ expression, which were normal then. The relative quantity of LOG₁₀E₂ in the case group was (6.69±0.05), while in the control group was higher (6.49±0.05). The relative quantity of LOG₁₀2MOE₂ in the case group was (3.82±0.07), while in the control group was (4.13±0.06). The LOG₁₀E₂ in the case group was significantly higher than that in the control group. The difference was statistical significance (P=0.013, P<0.05). While LOG₁₀2MOE₂ in the case group was significantly lower than that in the control group, the difference was statistical significance (P=0.001),The LOG₁₀E₂ in the case group was significantly higher than that in the control group. The difference was statistical significance (P=0.013,P<0.05). While LOG₁₀2MOE₂ in the case group was significantly lower than that in the control group, the difference was statistical significance (P=0.001,P<0.05).4 2MOE₂ is a product of E₂ via hydroxylation and then methylation. Then the ratio between the quantities of 24 hours E₂ and 2MOE₂ was calculated. The distribution of LOG₁₀E₂ /2MOE₂ was normal. The LOG₁₀E₂ /2MOE₂ in the case group(2.87±0.06) was significantly higher than that in the control group (2.37±0.08), the difference was significant (P=0.000,P﹤0.05).5 The case group was divided into stageâ… (13),â…¡(8) andâ…¢-â…£(11), The expression of LOG₁₀E₂ were not significantly different among three stages (P>0.05 ) by ANOVA. The expression of LOG₁₀E₂ in stageâ… was (6.61±0.33), (6.70±0.32) in stageâ…¡, (6.78±0.22) in stageâ…¢-â…£. No significant difference was found between every two stages by SNK test. While the expression of LOG₁₀2MOE₂ were not significantly different among the three stages (P>0.05 ) by ANOVA,which is (3.82±0.40) in stageâ… , (3.83±0.31) in stageâ…¡, (3.82±0.42) in stageâ…¢-â…£.6 The case group was divided into 2 groups according to cell differentiation: classâ…¡(25) and classâ…¢(7). The expressions of LOG₁₀E₂ were not significantly different between two stages (P>0.05 ),(6.68±0.29) in classâ…¡, (6.71±0.32) in classâ…¢. The expression of LOG₁₀2MOE₂ between two classes was not significantly different (P>0.05 ),(3.88±0.35) in classâ…¡, (3.62±0.42) in classâ…¢.7 The case group was divided into 2 groups: uterine infiltration≤1/2 (17) and uterine infiltration> 1/2 (15). The expression of LOG₁₀E₂ in the two levels were not significantly different between two groups (P>0.05 ),(6.62±0.27) in the group of uterine infiltration≤1/2, (6.77±0.31) in the group of uterine infiltratio>1/2. The expression of LOG₁₀2MOE₂ in the two levels were not significantly different between two groups (P>0.05 ),(3.85±0.34) in the group of uterine infiltration≤1/2, (3.79±0.42) in the group of uterine infiltration>1/2.Conclusion:1 The level of 2MOE₂ in the urine of endometrial cancer patients is low expressed, while higher in the normal urine, indicating that 2MOE₂ may play an important role in the inhibition of endometrial cancer ;2 The level of E₂ in in the urine of endometrial cancer patients is highly expressed, while lower in the normal urine, indicating that E₂ may play an important role in the occurrence of endometrial cancer ;3 E₂ /2MOE₂ in endometrial cancer urine is highly expressed, while lower in the normal urine, indicating that ratio of E₂ /2MOE₂ may be used as the indicator of endometrial cancer in high risk population;4 There is no significant correlation between E₂ and clinical stage, or cell stage, or uterine infiltration, either does 2MOE₂.