Correlation between Estrogen Receptorβ (ERβ), Neurofilament Protein (NF), and Protein Gene Product 9.5 (PGP9.5) Expressions as a Marker of Pain on Adenomyosis Etiopathogenesis

Arief Setiawan, Ruswana Anwar, Tita Husnitawati, Tono Djuwantono, Wiryawan Permadi


Adenomyosis is a pathological condition characterized by the presence of endometrial glands and stroma within the myometrium. Endometrial like cells development was influenced by local inflammatory reactions, increases local estradiol due to asynchromatized estrogen synthesis (ERβ) and then stimulated to proliferation and fibrosis, are also irritation on small nerve fibers in women with painful characterized symptoms on adenomyosis. There are expressions of neurofilament protein (NF) and protein gene product 9.5 (PGP 9.5) is a highly specific pan-neuronal marker for microfilament nerve fibers and is related to presenting pain with adenomyosis symptoms. A retrospective immunohistochemical study of thirty samples histopathological of adenomyosis as study groups and 30 with control groups between 25–49 ages which were established at Dr. Hasan Sadikin General Hospital and the satellites in April 2014–May 2015. This case-control analyzed ERβ, NF, and PGP 9.5 expressions compared and correlation between study groups and controls. The results showed there were significant differences in expression of ERβ, NF, and PGP 9.5 on adenomyosis higher than the control study (p<0.05). The intensity was higher and very strong into the study groups (p<0,001). Cut off point of ERβ was more than>6(sensitivity 66.7%; specificity 70%), NF>3 (sensitivity 93%; specificity 46%), PGP 9.5>4 (sensitivity 90%; specificity 67%). Odds Ratio (CI 95%) ERβ>6= 4.67; NF >3=12.25; PGP 9.5 >4=24.75 (p<0.001). The value of histoscore of ERβ and PGP9.5 have correlates to adenomyosis, the differences were statistically significant (p<0.05). The conclusion were that the adenomyosis had higher ERβ, NF, and PGP 9.5 expressions. There are simultant correlates and positive values between ERβ, NF, and PGP9.5 based on etiophatogenesis of pain on adenomyosis.


Adenomyosis, estrogen receptors β(ERβ), protein neurofilament (NF), protein gene product 9.5(PGP9.5)

Full Text:



Speroff L, Fritz MA. Adenomyosis. In : Clinical Gynaecologi Endocrinology and Infertility. 8th Ed. Philadelphia: Lippincott Williams and Walkins; 2011.

Mc Williams MM, Chennatukuzhi VM. Recent advances in uterine fibroid etiology. Semin Reprod J. 2017;35(2):181–9.

Taran FA, Stewart EA, Brucker S. Adenomyosis: Epidemiology risk factors clinical phenotypes and surgical interventional alternatives to hysterectomy. Geburtshiife und Frauenhelkunde. 2013;73(9):924–31.

Benagiano G, Habiba M, Brosen I. The pathophysiology of uterine adenomyosis : an update.Fertil Steril. 2012;98(3):572–9.

Novella M, Harraiz S. The effect of antiangiogenic treatment on peritoneal endometriosis-Associated nerve fibers. Fertil Steril. 2012;98:1209–17.

Wang Wen-Li, Hua D, Zhang. Expression of PGP95, NF and their reationship with dysmenorrhea in patients with adenomyosis. J Capital Medical Univ. 2012;(3):12.

Barcena de Arellano ML, Oldeweme J, Arnold J, Schneider A, Mechsner S. Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis. Fertil Steril. 2013;100(3):801–9.

Jean Baptise H, Tetrokalashvili M, Williams T, Fogel J. Characteristic associated with postoperative diagnosis of adenomyosis or combined adenomyosis with fibroids. Int J Gynecol Obstet. FIGO. 2013;122(2):112–4.

Vannucini S, Petraglia F. Recent advances in understanding and managing adenomyosis. Fertil Steril. 2019;8:283.

Mehasseb MK, Panchal R, Taylor AH, Brown L, Bell SC, Habiba M. Estrogen and progesterone receptor isoform distribution through the menstrual cycle with and without adenomyosis. Fertil Steril. 2011;95(7):2228–35.

Badawy AM, Elnasher AM, Mosbah AA. Aromatase inhibitors or gonadotropinj releasimh hormone agonists for management of uterine adenomyosis: randomized controlled trial. Acta Obstet Gynecol Scand. 2012;91:489–95.

Khreisat B, Al-Rawabeh, Duquom W, Al-Qudah M. Adenomyosis: Frequency of hysterectomy in histopathological specimens at two Jordanian Mil Hospitals. JRMS; 2011:76–9.

Al-Sabbagh M, Lam EW, Brosens JJ. Mechanism of endometrial progresterone resistance. J Mol Cell Endocrinol. 2012;358:208–15.

Pistofidis G, Makrakis E, Koukoura O, Bardis N, Balinakos P, Anaf V. Distinct types of uterine adenomyosis based on laparoscopic and histopatologic criteria. Clin Exp Obstet Gynecol. 2014;41(2):113–8.

Plante BJ, Lessey BA, Taylor RN, Wang W, Bagchi MK, Yuan L, et al. G protein coupled estrogen receptor (GPER) expression in normal and abnormal endometrium. Reprod Sci. 2012;19(7):684–93.

Tian R, Wang Z, Shi Z, Li D, Wang Y, Zhu Y, et al. Differential expression of G-protein coupled estrogen receptor 30 in human uterine myometrial smooth muscle. Fertil Steril. 2013;99(1):256–63.

Choi YJ, Chang JA, Kim YA, Chang SH, Chun KC, Koh JW. Innervation in women with uterine myoma and adenomyosis. Obstet Gynecol Sci. 2015;58(2):150–6.

Li. Y, Zhang.S, Xu.L. Expression of nerve growth factor produced by ectopic endometrium from patients with adenomyosis and its relationship with pain scales and innervation .J Fertil Sterile. 2014;27:287–91.

Hendry D, Madjid H.T, Ruswana A, Rachmawati A. Correlation expression immunocytochemistry vascular endothelial growth factor A (VEGFA) with protein gene product 9.5 (PGP 9.5) of menstrual blood on pathophysiologi endometriosis. Andalas Obstet Gynecol J. 2017;1(1):38–46.

Vinci V, Saldari M, Sergie E, Bernardo S, Rizzo G, Porpora G et al. Imaging MRI US or real time virtual sonography in the evaluation of adenomyosis. Radio Med J. 2017;122(5):361–8.


Article Metrics

Abstract view : 350 times
PDF - 294 times

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Creative Commons License
MKB is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License


View My Stats