Study On The Relationship Between Capsaicin Receptor And Estrogen Receptor Subtype Expression In Estrogen-dependent Endometrial Carcinoma

Background: Endometrial carcinoma was one of the three most malignant tumors of female genital tracts,taking up 20% to 30% of female genital tract tumors.The attack of endometrial carcinoma in the world was rising in recent years,there was a younger tendency,some of them were under40 years old,that seriously affecting the physical and mental health and social stability of the vast numbers of women.But the mechanism was not clear,the effective prevention targets and treatment of endometrial cancer has not been discovered.The histological type of endometrial cancer is divided into two types.Type I endometrial carcinoma occupys 70% to 80%,which malignant is low and occurrences due to a long-period estrogen stimulation.Capsaicin receptor TRPV1,which was found in recent years,was a kind of protein of nonselective cation channels,can be activated by capsaicin.TRPV1 was one of the family members of the transient receptor potential(TRP),widely distributed in cell membranes or intracellular organelles membrane in human body.TRPV1 played a significant role in many physiological functions.The current research suported that TRPV1 may improve and prevent some high risk factors of estrogen-dependent endometrial carcinoma.Animal experiments supported that TRPV1 can be expressed in endometrial glandular epithelium,and can be up-expressed under the regulation of estrogen.In the previous experiment,we have observed a decrease in the expression of capsaicin receptor in estrogen-d ependent endometrial carcinoma,but the expression was significantly higher than that in type II endometrial carcinoma;and in human endometrial carcinoma cell lines,High expression of Estrogen receptor ISHIKAWA endometrial cancer cell lines could express TRPV1 protein,and other low expression ER endom-etrial cancer cell lines without TRPV1 protein expression.It Suggested that the expression level of TRPV1 in estrogen-dependent endometrial carcinoma may be associated with estrogen receptor expression.The correlation between TRPV1 expression and estrogen receptor subtype expression in estrogen-dependent endometrial carcinoma is worthy of further study.Objective: This study aims to investigate the expression of TRPV1 and its relationship with ER subtype in estrogen-dependent endometrial carcinoma,and to explore the relationship between TRPV1 and ER subtype,and further reveal the mechanism of TRPV1 how to involv in the development process of estrogen dependent endometrial cancer.The study will provide new ideas and targets for the process of the clinical diagnosis and treatment of endometrial carcinoma.Methods:1 Case source: A total of 63 patients(mean age of 58.38 ± 8.68)with estrogen-dependent endometrial cancer confirmed by postoperative pathology were enrolled in the Second Hospital of Hebei Medical University.All of them were well-differentiated endometriosis Adenocarcinoma,staging by the surgical-pathologic staging criteria of the international union of gynecology and obstetrics(FIGO,2009).The control group selected 10 cases(mean age36.90±4.91)of normal proliferative endometrium(those women had been diagnosed as infertility caused by tubal reasons).2 Immunohistochemical staining: The expression of ER? and ER? and capsaicin receptor TRPV1 in estrogen-dependent endometrial carcinoma were detected by immunohistochemical SP method and DAB colorimetric assay.TRPV1 positive evaluation criteria: It is recognised as positive that Immunohistochemical staining emerges light yellow to tan particles in cell cytoplasm.Specific decision criteria: scoring according to the degree of tinting:no tinter calculating 0 point;Light yellow,a bit of higher than the background calculating 1 point;Tan,obviously higher than the background calculating 2 points;Strong dyeing,with brown calculating 3 points.At the same time according to the positive cell percentage scoring: < 5% calculating0 point;6% ~ 25% calculating 1 point;26% ~ 50% calculating 2 points;51%~ 75% calculating 3 points;> 75% calculating 4 points.It is divided into four levels after two scoring added: 0 ~ 1 point is judged as(-)negative,> 2 points are all positive,of which > 2 points are judged as(+)positive,3 ~ 4 points(++)medium positive,more than 5 points are judged as(+ + +)strong positive.ER positive evaluation criteria:Using the Allred score scoring system:Allred score is equal to the positive cell fraction plus positive intensity score.The proportion of positive cells: no nuclear staining(0 points),<l% nuclear staining(1 points),10% to 20% nuclear staining(2 points),from 11% to 33%nuclear staining(3 points),from 34% to 66% nuclear staining(4 points),and from the core of the dye(5 points).Positive intensity of the mean: negative(0points),weak positive(1 points),moderate positive(score)and strong positive(3 points),plus the results of the score range of 0 ~ 8.3-8 points as positive.3 Statistical method: Datas were analyzed by SPSS24.0 package of software statistically.Numeration data was indicated by n %(N/N),and measurement data was indicated by mean±standard deviation.We analyzed the relationship between the two groups by chi-square analysis.It is believed statistically significant if P<0.05.Results:1 General information: The experimental group selected 63 patients with type I endometrial tumor in stage I,including 43 cases of Ia,Ib in 20 cases.The control group selected 10 cases of normal proliferative endometrium(those women had been diagnosed as infertility caused by tubal reasons).2 Immunohistochemical results:2.1 The positive expression of TRPV1 is located in the cytoplasm and membrane of the cell.In 63 cases of endometrial carcinoma,the positive rate of TRPV1 expression was 73.02%(46/63),The positive expression score was1.59 ± 1.90.The positive rate of Ia was 81.40%(35/43),the positive rate of Ib was 55.5%(11/20).2.2 The positive expression of ER? is located in the nucleus.In 63 cases of endometrial carcinoma,the positive rate of ER? was 76.19%(48/63),Thepositive expression was 2.30±2.74.The positive rate of Ia was 83.72%(36/43),the positive rate of Ib was 60%(12/20).2.3 ER? positive expression in the nucleus.In 63 cases of endometrial carcinoma,the positive rate of ER? was 69.84%(43/63),The positive expression score was 2.72 ± 3.05.The positive rate of Ia was 76.74%(33/43),the positive rate of Ib was 50%(10/20).Statistical analysis showed that there was no obvious difference in the positive expression rates of TRPV1,ER? and ER? in 63 cases of endometrial carcinoma(x2=0.6445 P=0.7245).There was no significant difference in the positive expression rates of TRPV1,ER? and ER? in Ia and Ib endometrial carcinoma tissues(x2=0.6946,P=0.7066;x2= 0.4040,P= 0.8171).Further analysis of estrogen-dependent endometrial cancer ER?,ER? and TRPV1 positive expression score.(T=5.079,P= 0.00,r = 0.5158);the positive expression of ER? and TRPV1 was correlated(t=4.032,r=0.5158),and the positive expression of ER? and TRPV1 was correlated P=0.0001,r = 0.6827).Conclusion:1 In estrogen-dependent endometrial carcinoma,the positive expression of ER? and TRPV1 was correlated,the positive expression rate was not different,suggesting that TRPV1 and ER? participate in the pathogenesis of estrogen endometrial carcinoma.2 In estrogen-dependent endometrial carcinoma,the positive expression of ER? and TRPV1 was correlated,the positive expression rate was not different,suggesting that TRPV1 and ER? participate in the pathogenesis of estrogen endometrial carcinoma.