| Background and ObjectiveEndometrial carcinoma(EC) is a maligant disease which derives from normal epithelial, it's one of the most common maligant tumors in female genital tract. The incidence of endometrial carcinoma has a tendency of increase in the world. As we all know, long-term estrogen stimulation without progesterone counteraction play an important role in the development of EC, but the exact mechanism is still not very clear.A growing body of evidence has shown that in addition to the classical genomic mechanism of estrogen, estrogen combined with certain membrane proteins can rapidly activate cell signaling pathways. These estrogen effects that occur within minutes and cannot be attributed to a genomic mechanism, so these rapid effects have been designated as nongenomic effects of estrogen. The most likely combination with estrogen membrane protein candidate molecule in estrogen nongenomic effects is G protein-coupled receptor 30 (GPR30), it has become the focus of the study about the estrogen nongenomic effects mechanism. But the relationship between endometrial cancer and GPR30 still not very clear. So we studied the expression of GPR30 and P-AKT protein in different endomerium tissues by immunohistochemistry method, analysed their relationship and discussed their relationship with clinical pathological factors. To understand the possible molecular mechanism of endometrial carcinoma, supply possible indicator and offer a possible method for therapy.Materials and Methods1 Materials 114 endometrium tissues keeping in the archives in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University from March 2005 to April 2008 were included in the study, which consisted of 55 cases of endometrial carcinoma,49 cases of atypical hyperplasia of endometrium and 10 cases of normal endometrium tissues in proliferative phase. The patients age range from 26 years to 86 years, the mean age is 48.8±11.97 years, there is not obvious difference among these groups (P<0.05). The endometrial carcinoma were all endometrioid adenocarcinoma (stage I:37 cases, stageⅡ-Ⅲ:18 cases; and grade G1:35 cases, grade G2:16 cases, grade G3:74cases; 6 cases with pelvic lymph nodes metastasis, 49 cases without pelvic lymph nodes metastasis; muscular coat infiltration≤1/2:40 cases, muscular coat infiltration＞1/2:15 cases). The surgical-pathological stage of endometrial carcinoma was determined according to the 2000 International Federation of Obstetrics and Gynecology (FIGO) classification.2 Methods The expression of GPR30 and P-AKT protein in 114 cases of endometrium tissues were detected by immunohistochemistry S-P method to investigate the association between the positive rate of GPR30 or P-AKT with clinical-pathological characters of endometrial carcinoma and analyse the relativity of the two proteins.3 Statistical analysis All analyses were treated by the SPSS statistical package program 13.0. Evaluation the relationship between their expression and clinical-pathological factors by Chi-Square Test, the relationship between GPR30 and P-AKT evaluation by Phi correlation analysis of fourfold table. Statistically significant level was considered as "alpha equals 0.05" (α=0.05). Results1 The expression of GPR30 protein in different endometrium tissues and the relationship between GPR30 and clinical pathological factors. The positive rate of GPR30 in proliferative endometrium, endometrial hyperplasia and endometrial adenocarcinoma was 20%(2/10),67.3%(33/49) and 81.8%(45/55) respectively. The difference among proliferative endometrium, endometrial hyperplasia and endometrial adenocarcinoma were significant(χ2=15.778, P<0.001); After Chi-square divided, the difference between proliferative endometrium and endometrial hyperplasia or adenocarcinoma was significant(χ2=5.878, P=0.015;χ2=13.209, P< 0.001), but there was no significant between endometrial hyperplasia and endometrial adenocarcinoma(χ2=2.894, P=0.089). As to endometrial hyperplasia, Positive staining of GPR30 in SH, CH and AH was 30%(3/10),70%(14/20) and 84.2%(16/19) respectively, the difference among the three groups were significant(χ2=8.864, P=0.012); After Chi-square divided,the Positive rate of GPR30 in AH was significantly higher than that in SH(χ2=6.292, P=0.012), the difference between (AH+CH) and SH was also significant(χ2=5.978, P=0.014), but there was no difference between CH and AH or SH (χ2=0.452, P=0.501,χ2=2.868, P=0.090).In endometrial carcinoma, the Positive rate and level of GPR30 in surgical-pathological stageⅡ-Ⅲ(18/18,100%) was higher than 1(27/37,73%) in stage, there were significant difference between them(χ2=4.268, P=0.039). The positive rate of GPR30 expression in grade G1, grade (G2+G3) of endometrial carcinoma was 71.4%(25/35) and 100%(20/20) respectively, statistical significance were found in the two groups(χ2=5.196, P=0.023). The positive rate of GPR30 expression in postmenopause(10/16,62.5%) was higher than in premenopause(35/39, 89.7%), there were significant difference between them(χ2=3.977,P=0.046), Not found the positive rate of GPR30 have differences in lymph node metastasis or the depth of myometrial invasion.2 The expression of P-AKT protein in different endometrium tissues and the relationship between P-AKT and clinical pathological factors.The positive rate of P-AKT in proliferative endometrium, endometrial hyperplasia and endometrial adenocarcinoma was 20%(2/10),71.4%(35/49) and 78.3%(43/55) respectively. The difference among proliferative endometrium, endometrial hyperplasia and endometrial adenocarcinoma were significant(χ2=13.750, P=0.001); After Chi-square divided, the difference between proliferative endometrium and endometrial hyperplasia or endometrial adenocarcinoma was significant(χ2=7.323, P=0.007;χ2=10.854, P=0.001), but there was no significant between endometrial hyperplasia and endometrial adenocarcinoma(χ2=0.630, P=0.427). As to endometrial hyperplasia, Positive staining of P-AKT in SH,CH and AH was 40%(4/10),65.0%(13/20) and 94.7%(18/19) respectively, the difference among the three groups were significant(χ2=10.303, P=0.006); After Chi-square divided, the Positive rate of P-AKT in AH was significantly higher than that in SH(χ2=7.939, P=0.005), the difference between (AH+CH) and SH was also significant(χ2=4.300, P=0.038), but there was no difference between CH and AH or SH(χ2=3.618, P=0.057,χ2=0.831, P=0.362).In endometrial carcinoma, the expression rate and level of P-AKT in surgical-pathological stage 1(25/37,67.6%) was lower than in stage 11-111(18/18, 100%), there were significant difference between them(χ2=5.687, P=0.017). The positive rate of P-AKT expression in grade G1, grade (G2+G3) of endometrial carcinoma was 65.7%(23/35) and 100%(20/20) respectively, statistical significance were found in the two groups(χ2=6.876, P=0.009). The positive rate of P-AKT expression in postmenopause (9/16,56.3%) was higher than in premenopause (34/39, 87.2%), there were significant difference between them(χ2=4.679, P=0.031). The positive rate of P-AKT was higher in endometrial adenocarcinoma with deep myometrial invasion(χ2=4.131, P=0.042). Not found the positive rate of P-AKT have differences between lymph node metastasis and Without lymph node metastasis endometrial carcinoma.The relationship between the GPR30 protein and P-AKT protein expression in endometrial cancer was positively correlated(rp=0.550,χ2=16.634, P<0.001).Conclusions1 GPR30 and P-AKT protein showed high expression in endometrium of endometrial adenocarcinoma, while showed low expression in the atypical hyperplasia group and the normal endometrium group. There was a close relationship between the positive rate of GPR30 and P-AKT with surgical-pathological stages, histological differentiation, postmenopause. It proved that GPR30 and P-AKT might play an important role in the development of endometrical carcinoma.2 In endometrial carcinoma,the expression of GPR30 protein is correlated with that of P-AKT protein,implying that GPR30 may cooperate with P-AKT in endometrial development, they may play a synergistic role in the occurrence and development of endometrial carcinoma.
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