{"paper_id":"6fe0b693-3ed5-4c70-b3ef-047f1e80bceb","body_text":"R E S E A R C H Open Access\nDecreased expression of survivin, estrogen and\nprogesterone receptors in endometrial tissues\nafter radiofrequency treatment of dysfunctional\nuterine bleeding\nGeping Yin *, Tongyu Zhu, Juan Li, Ming Chen, Shujun Yang and Xiaoli Zhao\nAbstract\nBackground: The purpose of the research is to study the histopathology and expression of survivin, estrogen and\nprogesterone receptors (ER/PR) in the endometrium of patients with dysfunctional uterine bleeding (DUB) treated\nwith radiofrequency endometrial ablation (REA).\nMethods: A total of 98 DUB patients were enrolled in this case –control study. Among them, 66 underwent REA\ntreatment and 32 optioned for hormone therapy as the control group. Immunohistochemical analysis for survivin,\nER and PR expression was carried out on endometrial tissue samples collected before and 6 to 7 months after\ntreatment for both groups.\nResults: Both hormone and REA treatment ameliorated menstrual bleeding of DUB patients, with the latter\nshowing a significantly higher effective rate. Endometrial surface tissue was replaced by fibrosis tissue in the REA\ntreatment group. REA treatment also significantly reduced the expression of survivin, ER, and PR. Endometrial\nsurface tissues collected from the hormone-treated control group neither showed any apparent morphological\nalteration nor in the expression of those receptors.\nConclusions: REA treatment changed endometrial surface tissue type from gland rich to gland poor, and\nsignificantly decreased the expression of survivin, ER, and PR. This may be an important contributing mechanism for\nthe long-term curative effect and prevention of DUB recurrence.\nKeywords: Dysfunctional uterine bleeding (DUB), Radiofrequency endometrial ablation (REA), Survivin, Estrogen\nreceptor (ER), Progesterone receptor (PR)\nBackground\nDysfunctional uterine bleeding (DUB) is a common\ngynecological disease, affecting 19% of women of child-\nbearing age and perimenopausal women [1,2]. The treat-\nment options usually include drugs or surgery, both of\nwhich have significant disadvantages such as recurrence of\nthe symptoms and dysfunctional uterus [2-5]. How to\nimprove the efficacy of minimally-invasive surgery has\nbecome a widely-recognized concern [6,7]. Radiofrequency\nendometrial ablation (REA) is a minimally-invasive tech-\nnique recently developed in gynecology [8-12]. After\ndelivering a radiofrequency source into the uterine cavity\na thermal effect (approximately 60-85°C) is produced\nwhich causes thermocoagulation, denaturation, and necro-\nsis of endometrial tissue, as well as peripheral vascular\nthrombosis, which stops the bleeding [12].\nThere were histopathological studies on the treatment\nof menorrhagia using thermocoagulation endometrial\nablation [2,6]. However, study of the histopathology and\nthe expression for survivin, estrogen receptors (ER), and\nprogesterone receptors (PR) in the endometrium of\nDUB patients after REA is lacking. Therefore, the\ncurrent study was aimed to evaluate the histopathology\nand expression of survivin, ER, and PR in the endomet-\nrium of DUB patients, using conventional histological\n* Correspondence: ygpwylll@hotmail.com\nDepartment of Obstetrics & Gynecology, Jinan Military General Hospital, #25\nShifan Road, Jinan 250031, China\nWORLD JOURNAL OF \nSURGICAL ONCOLOGY \n© 2012 Yin et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative\nCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and\nreproduction in any medium, provided the original work is properly cited.\nYin et al. World Journal of Surgical Oncology 2012, 10:100\nhttp://www.wjso.com/content/10/1/100\n\nand immunohistochemical techniques. The association\nof changes of these molecules and the potential long-\nterm effectiveness mechanism after REA treatment was\nassessed.\nMethod\nClinical data\nPatient population\nThis was a prospective study. The patient inclusion cri-\nteria were: age > 30 years without the desire of fertility, a\nclear diagnosis of DUB, pictorial blood loss assessment\nchart (PBAC) [13] >100, and benign endometrial prolif-\nerative lesions without cellular atypia confirmed by cur-\nettage pathology during the period of persistent\nabnormal uterine bleeding; and those who provided\ninformed consent for treatment and research. The study\nwas approved by the Institutional Review Board. The\nprocedures were in accordance with the ethical stan-\ndards of the responsible local or national committee on\nhuman experimentation and with the Helsinki Declar-\nation (1975, revised 1983, World Medical Association\nDeclaration of Helsinki). Patients who did not complete\nthe follow-up or who had malignant gynecological can-\ncer or other serious internal illness (including severe\nheart diseases, liver cirrhosis, and cerebral thrombosis)\nwere excluded from the study. A total of 98 DUB\npatients were consecutively enrolled from June 2007 to\nJune 2010. None of them had endometrial carcinoma.\nThe REA group consisted of 66 DUB patients, all Han\nChinese, with an average age of 42.5 years (range 33 –\n50 years), and a pre-treatment PBAC score of\n182.5 ± 67.5 (time from treatment to endometrial curet-\ntage ranged from 6.5 to 12 months, with an average\n9.1 ± 3.0 months). The treatment effect was defined as\neither a curative effect (post-treatment PBAC score <80),\nsignificant effect (PBAC score of 80 –100), or treatment\nfailure (PBAC score > 100). The rate of treatment effect-\niveness was defined as the sum of the curative effect and\nsignificant effect rates.\nThe control group was enrolled by 1:2 and consisted\nof 32 DUB patients who met the study eligibility criteria\nand opted for hormone therapy. Their average age was\n43.5 years (range 32 –48 years) and their pre-treatment\nPBAC score was 177.0 ± 67.8. Each patient began with\nprogesterone-norethindrone (Shanghai Xinyikangjie\nPharmaceutical Inc., Shanghai, China) at 5.0 mg every\n8 h for 2 –3 days. After the bleeding stopped, the dosage\nwas reduced by one-third every 3 days until the daily\nmaintenance dose of approximately 2.5-5.0 mg was\nreached. Patients then continued the treatment to\n21 days post-hemostasis. If the symptoms of DUB re-\ncurred months later, hormone therapy was repeated. If\nthe symptoms of DUB exacerbated, other treatment,\nsuch as hysterectomy, was considered.\nEndometrial specimens were collected by curettage be-\nfore treatment and post-treatment (6 to 7 months) for\nboth the REA treated and the hormone-treated control\ngroups.\nREA treatment\nThe Kangpu XVC-III gynecological RF therapy device\n(Xi’an Vize Electronic Technology Co. Ltd., Xi ’an, China)\nwas used for REA with the following technical para-\nmeters: 220 v ± 10%, 50 Hz ± 2%, P ≤ 60 w, I <2 A, 600\nKHz ± 15%, power setting in the 40 w.\nREA procedure According to preoperative hysteroscopy\ndata and guided by the color Doppler ultrasound, the\ncoagulator was delivered to the bottom of the uterine\ncavity. After the coagulator was turned on, the active\nsurface contacted the uterus membrane. From top to\nbottom, left to right, the coagulator was moved inside\nthe uterine cavity in two circles, with the speed of 1 cm\nevery 6 –12 s. When moved to the left or right, the dis-\ntance was the width of a coagulator. Movement was\nmade between the anterior and posterior wall of the\nuterus three times, and the left and right side wall once\n(the whole procedure generally took 10 to 15 min to\ncomplete).\nHistopathology and immunohistochemical assay\nReagents and materials include: (1) conventional histo-\nlogical reagents including paraffin embedding materials,\nH&E staining solutions, and so on; and (2) for immuno-\nhistochemistry, mouse monoclonal antibodies against\nhuman survivin, ER, and PR (NeoMarkers Products,\nUSA) and universal streptomycin avidin-peroxidase\nhypersensitive (SP) staining kit (Santa Cruz Products,\nGermany).\nHistology and immunostaining\nEndometrial biopsy samples were embedded with paraf-\nfin, and serial sections at 4 μm thickness were prepared.\nSome sections underwent regular H&E staining. Other\nsections were processed for immunostaining for survi-\nvin, ER, and PR, as described in details below.\nSections were deparaffinized, rehydrated, and under-\nwent antigen retrieval process using ethylenediaminete-\ntraacetic acid (EDTA) solution. After washing in 0.1 M\nPBS, sections were incubated overnight in primary anti-\nbodies for survivin, ER or PR at 4°C. The sections were\nthen incubated successively in biotinylated secondary\nantibody (reagent C) for 10 min; streptomycin-\nperoxidase solution (reagent D) for 10 min; and followed\nby freshly prepared DAB/H2O2 solution from the stain-\ning kit for 2 –10 min. After a further wash in PBS, the\nsections were counterstained with hematoxylin, dehy-\ndrated, and mounted with neutral gum for microscopic\nYin et al. World Journal of Surgical Oncology 2012, 10:100 Page 2 of 6\nhttp://www.wjso.com/content/10/1/100\n\nexamination and photography. Methodological controls\nincluded using known positive sections as the positive\ncontrol, and omission of primary antibodies or their re-\nplacement with PBS as the negative control.\nAssessment of immunohistochemical assay\n(1) Survivin immunohistochemical staining scoring\ncriteria (ISSC): Survivin expression was primarily\nlocalized in the cytoplasm of endometrial epithelial\ncells and occasionally in the nucleus. Brown-yellow\ngranules in the cytoplasm and/or nuclei indicated\npositive (positive cells). Ten randomly selected fields\nwere examined under light microscope for each\nsection. The scoring was based on the following two\nscales: A. The intensity of staining: 0 points for no\nstaining, 1 point for weak staining, 2 points for\nmoderate staining, and 3 points for intense staining;\nB: The percentage of positive cells in all cells\ncounted: 0 point if positive cell is ≤ 5%, 1 point =\n6-25%, 2 points = 26-50%, and 3 points if ≥ 51%. The\ncombination of these two scales for each section\nwas used as the score for survivin immunostaining\n(ranged between 0 –9 in total). This score was\nconsidered as the level of survivin expression in the\nstudy, and the mean and standard deviation were\ncalculated for each group.\n(2) ER and PR ISSC: ER and PR expression were mainly\nlocalized in the nucleus of endometrial epithelial\ncells and stromal cells. Brown-yellow granules in the\nnucleus and/or cytoplasm indicated positive\n(positive cells). Ten randomly chosen fields were\nexamined under light microscope for each section.\nThe percentage of positive cells was quantified by\ncounting 100 cells in total for each field. The mean\nand standard deviation of the percentage of positive\ncells were calculated for all fields examined.\nStatistics\nThe Student t-test was used for continuous data, and\nthe χ2 test was used for categorical data. Commercially\navailable software was used to perform the tests (SPSS\n13.0). Statistical significance was defined as P <0.05.\nResults\nThe effect on DUB of the hormone-treated control and\nthe REA-treated groups\nThere was no statistical difference between REA and the\ncontrol group on geographic distribution, ethnicity, age,\npre-treatment PBAC scores, and time from treatment to\ncurettage ( P > 0.05). In the control group, the PBAC\nscore decreased from 177.0 ± 67.8 at baseline to\n120 ± 70.2 at 8.5 months (8.5 ± 2.5 months) post-treat-\nment, which was statistically significant ( P < 0.05). The\ntotal effective rate of DUB was 56.3% (18/32 cases- there\nwere 14 patients whose symptoms of DUB recurred\nmonths later, exacerbated after another course of hor-\nmone therapy and eventually undertook hysterectomy).\nIn the REA group, the PBAC score decreased from\n182.5 ± 67.5 at baseline to 56.7 ±22.0 at 9.1 months\n(9.1 ± 3.0 months) post-treatment, which showed a\ngreater significant difference ( P < 0.01). In addition, the\nreduction of the PBAC scores from baseline to post\ntreatment follow-up was significantly higher in the REA\ngroup (125.8 ± 44.5) than in control group (57.2 ± 37.5)\n(P < 0.01). Furthermore, the total effective rate of the\nREA group reached 95.5% (63/66 cases), which was also\nhigher than that in the control group (95.5% vs. 56.3%,\nP < 0.05). These results indicate that REA had better\ntreatment effects than the hormone therapy.\nEndometrial histopathology before and 6 to 7 months\nafter REA\nTables 1 and 2 list changes of the pathology type before\nand after treatment in both groups. Prior to treatment,\nDUB patients in the REA group showed benign prolif-\nerative endometrial glands, some of which were irregu-\nlarly enlarged and closely arranged into a ‘back to back ’\nshape (Figure 1A). After 6 to 7 months of REA, most\nendometrial tissues were shown to be replaced by granu-\nlation tissue, and only small amounts of glands remained\nwhich were small in size, and surrounded by fibrosis tis-\nsue (Figure 1B).\nχ\n2 test showed that there was no significant difference\nin the endometrial pathological types between the two\ngroups before any treatment ( P > 0.05). In the control\ngroup there was no significant difference in the\nTable 1 The changes of the pathology type before and after treatment in control groups\nHistopathological types Control groups n (%) Statistics\nBefore treatment After treatment χ2 P\nFibrous connective tissue and granulation tissue 0 (0.0%) 0 (0.0%) - -\nSome endometrial glands and granulation tissue 0 (0.0%) 0 (0.0%) - -\nProliferative endometrium 8 (25.0%) 15 (46.9%) 3.326 >0.05\nSimple hyperplasia 14 (43.8%) 12 (37.5%) 0.259 >0.05\nComplex hyperplasia 10 (31.2%) 5 (15.6%) 2.177 >0.05\nStatistics is Fisher probabilistic method (compared with before treatment). n, number of cases.\nYin et al. World Journal of Surgical Oncology 2012, 10:100 Page 3 of 6\nhttp://www.wjso.com/content/10/1/100\n\npathological types before and after the hormone treat-\nment ( P > 0.05). In contrast, there was a significant dif-\nference between the pathological types before and after\ntreatment in the REA group ( P < 0.01). In addition, REA\ntreated group showed a significant difference in the\npathological types when compared with the control\ngroup ( P < 0.01).\nExpression of survivin, ER, and PR expression before and\n6 to 7 months after treatment in the control group\nThe analysis showed that prior to the hormone treat-\nment, the average expression for all three molecules\n(survivin, ER, and PR) were higher in endometrial tissues\nwith complex hyperplasia than those with simple hyper-\nplasia or proliferative endometrium, but the differences\nwere not significant ( P > 0.05). The mean levels of three\nmolecules slightly decreased after the hormone treat-\nment, but again the differences were not significant\n(P > 0.05) (Table 3).\nExpression of survivin, ER, and PR before and 6 to 7\nmonths after treatment in REA treatment group\nBefore REA, the expression of survivin was strong in the\ncytoplasm of glandular cells (Figure 1C). After REA (6 to\n7 months follow-up), it was weak (Figure 1D) (Figure 1\nE, F, G, H, Table 4).\nBefore treatment, the expression levels of survivin, ER,\nand PR were not significantly different between the REA\nand control groups ( P > 0.05). After treatment, there was\na significant reduction in the expression of these three\nmolecules in the REA group ( P < 0.05). The differences\nin the levels of survivin, ER, and PR expression before\nand after treatment were also greater in the REA group\nthan those in the control group ( P < 0.05).\nComplications associated with RF procedure and\ntreatment/prevention measures\nAbdominal pain occurred within 24 h after treatment in\n30.3% (20/66) of RF subjects. Endometrial coagulation\nnecrosis can stimulate uterine cramps and contractions\nthat may result in abdominal pain, usually occurring\nwithin 12 h of treatment. Patients were treated for\nTable 2 The changes of the pathology type before and after treatment in REA groups\nHistopathological types REA group n (%) Statistics\nBefore treatment After treatment χ2 P\nFibrous connective tissue and granulation tissue 0 (0.0%) 20 (30.3%) 23.030 <0.01\nSome endometrial glands and granulation tissue 0 (0.0%) 27 (40.9%) 32.832 <0.01\nProliferative endometrium 16 (24.2%) 13 (19.7%) 0.461 >0.05\nSimple hyperplasia 30 (45.5% 4 (6.1%) 25.611 <0.01\nComplex hyperplasia 20 (30.3%) 2 (3.0%) 17.220 <0.01\nStatistics is Fisher probabilistic method (compared with before treatment).\nn, number of cases; REA, radiofrequency endometrial ablation.\nFigure 1 Endometrial pathology and survivin, ER, and PR\nexpression before and 6 to 7 months after REA treatment in\nDUB patients with complex endometrial hyperplasia. (A) Before\nREA, the endometrium showed complex hyperplasia, ‘back to back ’\nglandular hyperplasia, leather bag shape glandular enlargement. ( B)\nSix to seven months after REA, glandular tissue became fibrous\ntissue with scarce glands and blood vessels in endometrial\ncurettage. (C) Before REA, the expression of survivin (strong positive).\n(D) Six months after REA, the expression of surviving showed weak\npositive. (E) Before REA, the expression of ER (strong positive). ( F) Six\nmonths after REA, the expression of ER showed weak positive. ( G)\nBefore REA, the expression of PR (strong positive). ( H) Six months\nafter REA, the expression of PR showed weak positive. DUB,\ndysfunctional uterine bleeding; ER, Estrogen receptors; PR,\nProgesterone receptor; REA, Radiofrequency endometrial ablation.\nYin et al. World Journal of Surgical Oncology 2012, 10:100 Page 4 of 6\nhttp://www.wjso.com/content/10/1/100\n\nabdominal pain with atropine (1.0 mg intramuscular\ninjection).\nThe incidence of post-treatment intrauterine adhe-\nsions was 7.6% (5/66); no severe adhesions presented. At\n1 and 3 months post-operation, the uterine cavity was\nexamined for adhesions using a No. 4 cervical dilator. In\nyoung women, an intrauterine device (IUD) was inserted\nas a means to separate the adhesions, or the adhesions\nwere separated under hysteroscopy. Infection control\nwas provided with the prescription of routine antibiotics\nfor 1 to 2 weeks after treatment; no severe endometritis\nor pelvic inflammatory disease occurred among the\npatients.\nDiscussion\nThe endometrium of patients with anovulatory DUB is\ncontinuously stimulated by estrogen without the antag-\nonism of progesterone, resulting in various degrees of\nproliferative changes followed by repeated bleeding [1].\nThermalcoagulation effects of REA can directly inacti-\nvate the estrogen and progesterone receptors in the le-\nsion. However, the literature on the expression of\nestrogen and progesterone receptors and survivin in the\nrepaired tissues at 6 to7 months after treatment is lack-\ning. This might be important in understanding whether\nREA can provide long-term effects beyond temporary\nhemostasis.\nThe action of REA treatment on DUB\nIn medical physics, sinusoidal alternating current with a\nfrequency greater than 100 kHz is called radio frequency\n(RF). As RF can create a thermal effect (approximately\n60-85°C) in biological tissues at an approximate depth of\ntreatment of 5 –7 mm, a coagulator can cause the follow-\ning changes in endometrial tissue to achieve the purpose\nof DUB treatment: (1) direct thermal coagulation and\nnecrosis or apoptosis of the endometrial functional layer\nand the basal cell layer; (2) peripheral intravascular co-\nagulation around the lesion and bleeding cessation; and\n(3) gradual replacement of endometrial tissues by fibrous\nconnective tissue that do not ablate periodically. The\nhistopathology data from this study showed decreases in\nsimple hyperplasia and complex hyperplasia, and\nincreases in gland-free fibrous connective tissue and\ngranulation tissue with fewer endometrial glands in the\nendometrium following REA treatment.\nThe effects of REA on survivin, ER, and PR and potential\nmechanism for long-term effectiveness on DUB\nThe survivin gene is the only one in the inhibitor of\napoptosis proteins (IAP) family that was found to be\nrelated to both apoptosis and the regulation of the cell\ncycle. Studies have shown that survivin has partial or\ncomplete low expression in the normal endometrium,\nwhich may be due to the active proliferation of endo-\nmetrial cells [14,15]. The expression of PR and ER in\nendometrial cells of patients with anovulatory DUB was\nfound higher than normal, and was positively correlated\nwith the degree of endometrial proliferation [16,17].\nThe histopathologic results of the study showed that\nREA can directly cause the coagulation, necrosis, col-\nlapse, occlusion, and disappearance of glandular lumen\nin the endometrium. The endometrium was gradually\nreplaced by fibrous granulation tissue that does not ab-\nlate periodically, which may lead to the reduction of\nmenstrual flow or amenorrhea. Immunohistochemical\ndata of the study showed that the expression levels of\nsurvivin, ER, and PR in fibrous granulation tissue after\nREA treatment were significantly reduced, and were also\nsignificantly lower than those in the hormone treated\nTable 3 Endometrial tissues survivin, ER, and PR expression before and after treatment in the control group\nPathology before treatment n Before treatment (mean ± SD) After treatment (mean ± SD)\nSurvivin scores ER (%) PR (%) Survivin scores ER (%) PR (%)\nProliferative endometrium 8 5.5 ± 1.2 53.3 ± 18.1 40.6 ± 27.3 5.7 ± 1.8 55.6 ± 30.1 51.8 ± 37.0\nSimple hyperplasia 14 6.1 ± 1.8 58.1 ± 16.3 44.7 ± 262 5.9 ± 1.6 57.6 ± 34.3 50.7 ± 30.1\nComplex hyperplasia 10 8.5 ± 2.0 86.2 ± 36.2 85.3 ± 21.5 6.7 ± 2.3 82.7 ± 32.1 77.1 ± 36.4\nThe comparisons were between before and after treatment.\nn, number of cases; ER, estrogen receptor; PR, progesterone receptor.\nTable 4 Endometrial tissues survivin, ER, and PR expression before and after treatment in the REA group\nPathology before treatment n Before treatment (mean ± SD) After treatment (mean ± SD)\nSurvivin scores ER (%) PR (%) Survivin scores ER (%) PR (%)\nProliferative endometrium 16 5.7 ± 1.7 53.3 ± 18.3 45.9 ± 22.3 2.5 ± 1.7 a 23.8 ± 10.4a 11.3 ± 7.5a\nSimple hyperplasia 30 7.2 ± 1.7 51.4 ± 15.7 54.2 ± 25.7 1.8 ± 0.9 a 18.9 ± 14.4a 26.9 ± 11.3a\nComplex hyperplasia 20 8.1 ± 2.3 79.9 ± 20.4 86.7 ± 31.6 2.9 ± 0.3 a 18.3 ± 12.1a 21.4 ± 6.8a\nThe comparisons were between before and after treatment.\naP <0.05.\nn, number of cases; ER, estrogen receptor; PR, progesterone receptor; REA, radiofrequency endometrial ablation.\nYin et al. World Journal of Surgical Oncology 2012, 10:100 Page 5 of 6\nhttp://www.wjso.com/content/10/1/100\n\ncontrol group. At 6 to 7 months post-treatment, the\nexpression of survivin, ER, and PR from the scattered\nglands in the fibrous endometrium remained low, which\nis likely to result in a diminished response to estrogen\nand progesterone stimulation. The decreased expression\nof the receptors would suggest a suppressed binding abil-\nity to estrogen and progesterone. Whether the suggestion\nis another mechanism for the DUB recurrence-prevention\nand long-term effectiveness of REA treatment needs\nfurther studies.\nConclusions\nREA treatment changed endometrial surface tissue type\nfrom gland rich to gland poor, and significantly decreased\nthe expression of survivin, ER, and PR. This may be an\nimportant contributing mechanism for the long-term\ncurative effect and prevention of DUB recurrence.\nAbbreviations\nDUB: Dysfunctional uterine bleeding; EDTA: Ethylenediaminetetraacetic acid;\nER: Estrogen; HE: Hematoxylin-eosin; ISSC: Survivin immunohistochemical\nstaining scoring criteria; PBAC: Pictorial blood loss assessment chart;\nPR: Progesterone receptors; REA: Treated with radiofrequency endometrial\nablation.\nCompeting interests\nThe authors declare that the authors have no competing interests.\nAuthors’ contributions\nGY conceived and designed the experiments, performed the experiments\nand wrote the paper. JL and SY performed the experiments. TZ analyzed the\ndata. MC and XZ contributed materials and analysis tools. All authors read\nand approved the final manuscript.\nAcknowledgements\nThe study was funded by the key fundings of the Jinan Military General\nHospital and Health Department of Jinan Military. The funding source had\nno role in the study design, the collection and interpretation of the data,\nwriting of the report, or decision to submit the paper for publication.\nReceived: 20 January 2012 Accepted: 26 March 2012\nPublished: 1 June 2012\nReferences\n1. Amir E, Richard HS: Dysfunctional uterine bleeding. 2010, http://\nemedicine.medscape.com/article/795587-overview.\n2. Apgar BS, Kaufman AH, George-Nwogu U, Kittendorf A: Treatment of\nmenorrhagia. Am Fam Physician 2007, 75:1813–1819.\n3. Hodgson DA, Feldberg IB, Sharp N, Cronin N, Evans M, Hirschowitz L:\nMicrowave endometrial ablation: development, clinical trials and\noutcomes at three years. Br J Obstet Gynecol 1999, 106:684–694.\n4. Li D: The curative effect of RU486 for the treatment of dysfunctional\nuterine bleeding (in Chinese - English abstract available). Chin J Mod\nDrug Appl 2009, 3:104–105.\n5. Xiu-min F: Clinical analysis of mifepristone treatment of 68 cases of\nperimenopausal dysfunctional uterine bleeding (in Chinese - English\nabstract available). Medical Information 2010, 23:905–906.\n6. Zarek S, Sharp HT: Global endometrial ablation devices. Clin Obstet Gynecol\n2008, 51:167–175.\n7. Taskin O, Onoglu A, Inal M, Turan E, Sadik S, Vardar E, Postaci H, Wheeler JM:\nLong-term histopathologic and morphologic changes after thermal\nendometrial ablation. J Am Assoc Gynecol Laparosc 2002, 9:186–190.\n8. Thijssen RF: Radiofrequency induced endometrial ablation: an update. Br\nJ Obstet Gynaecol 1997, 104:608–613.\n9. Dequesne JH, Gallinat A, Garza-Leal JG, Sutton CJ, van der Pas HF,\nWamsteker K, Chandler JG: Thermoregulated radiofrequency endometrial\nablation. Int J Fertil Womens Med 1997, 42:311–318.\n10. Clark TJ, Samuel N, Malick S, Middleton LJ, Daniels J, Gupta JK: Bipolar\nradiofrequency compared with thermal balloon endometrial ablation in\nthe office: a randomized controlled trial. Obstet Gynecol 2011,\n117:109–118.\n11. El-Nashar SA, Hopkins MR, Creedon DJ, Cliby WA, Famuyide AO: Efficacy of\nbipolar radiofrequency endometrial ablation vs thermal balloon ablation\nfor management of menorrhagia: A population-based cohort. J Minim\nInvasive Gynecol 2009, 16:692–699.\n12. Yin GP, Chen M, Shao X, Zhu TY, Wang YZ: Radiofrequency minimally\ninvasive treatment of uterine benign diseases (in Chinese - English\nabstract available). Progress Obstetrics and Gynecology 2003, 12:200–203.\n13. Higham JM, O ’Brien PM, Shaw RW: Assessment of menstrual blood loss\nusing a pictorial chart. BJOG 1990, 97:734–739.\n14. Takai N, Miyazaki T, Nishida M, Nasu K, Miyakawa I: Survivin expression\ncorrelates with clinical stage, histological grade, invasive behavior and\nsurvival rate in endometrial carcinoma. Cancer Lett 2002, 184:105–116.\n15. Chen X, Zhang Z, Feng Y, Fadare O, Wang J, Ai Z, Jin H, Gu C, Zheng W:\nAberrant survivin expression in endometrial hyperplasia: another\nmechanism of progestin resistance. Modern Pathology 2009, 22:699–708.\n16. Hu K, Zhong G, He F: Expression of estrogen receptors ERalpha and\nERbeta in endometrial hyperplasia and adenocarcinoma. Int J Gynecol\nCancer 2005, 15:537–541.\n17. Kalogiannidis I, Bobos M, Papanikolaou A, Makedos A, Amplianitis I, Vergote\nI, Nenopoulou E, Makedos G: Immunohistochemical bcl-2 expression, p53\noverexpression, PR and ER status in endometrial carcinoma and survival\noutcomes. Eur J Gynaecol Oncol 2008, 29:19–25.\ndoi:10.1186/1477-7819-10-100\nCite this article as: Yin et al. : Decreased expression of survivin, estrogen\nand progesterone receptors in endometrial tissues after radiofrequency\ntreatment of dysfunctional uterine bleeding. World Journal of Surgical\nOncology 2012 10:100.\nSubmit your next manuscript to BioMed Central\nand take full advantage of: \n• Convenient online submission\n• Thorough peer review\n• No space constraints or color figure charges\n• Immediate publication on acceptance\n• Inclusion in PubMed, CAS, Scopus and Google Scholar\n• Research which is freely available for redistribution\nSubmit your manuscript at \nwww.biomedcentral.com/submit\nYin et al. World Journal of Surgical Oncology 2012, 10:100 Page 6 of 6\nhttp://www.wjso.com/content/10/1/100","source_license":"CC0","license_restricted":false}