Top

Published in:

01-07-2018 | Original Article

Investigation of hormone receptor expression and its prognostic value in endometrial stromal sarcoma

Authors: Jeong-Yeol Park, Min-Hyun Baek, Yangsoon Park, Young-Tak Kim, Joo-Hyun Nam

Published in: Virchows Archiv | Issue 1/2018

Abstract

To evaluate the immunohistochemical (IHC) expression of hormone receptors and analyze the prognostic implication of these receptors in patients with endometrial stromal sarcoma (ESS). Fifty-one patients with ESS whose paraffin blocks and pathologic slides, which were obtained after hysterectomy, were available and included in this study. Clinicopathologic data were gathered from patients’ medical records, and IHC staining of hormone receptors was performed using tissue microarrays. Estrogen receptor (ER)-alpha was expressed in 37 patients (72.5%), and strong immunoreactivity was observed in 27 patients (52.9%). However, ER-beta expression was observed in only two patients (3.9%). Progesterone receptor (PR) expression was identified in 36 patients (70.6%), and strong immunoreactivity was found in 26 patients (51%). Androgen receptor (AR) expression was observed in 30 patients (58.8%), and strong immunoreactivity was noted in 14 patients (27.5%). Gonadotropin-releasing hormone receptor (GnRH-R) expression was observed in 49 patients (96.1%), but no patient exhibited strong immunoreactivity. All patients expressed CYP19A1, and 43 patients (84.3%) had strong immunoreactivity. ER-alpha, PR, and AR positivity was associated with significantly better overall survival (OS). No patient with AR positivity died of ESS. When the patients were categorized according to ER-alpha, PR, and AR immunoreactivity, triple-positive ESS had the best OS, and triple-negative ESS was linked to the worst OS. Expression of hormone receptors was associated with favorable survival outcome in ESS. Hormone receptors that showed strong expression deserve further evaluation to clarify their importance as a therapeutic target and predictor of treatment response.

Available only for authorised users

Abeler VM, Royne O, Thoresen S, Danielsen HE, Nesland JM, Kristensen GB (2009) Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 54:355–364. https://doi.org/10.1111/j.1365-2559.2009.03231.x CrossRefPubMed

Altman AD, Nelson GS, Chu P, Nation J, Ghatage P (2012) Uterine sarcoma and aromatase inhibitors: tom baker Cancer Centre experience and review of the literature. Int J Gynecol Cancer 22:1006–1012. https://doi.org/10.1097/IGC.0b013e31825b7de8 CrossRefPubMed

Amant F, Floquet A, Friedlander M, Kristensen G, Mahner S, Nam EJ, Powell MA, Ray-Coquard I, Siddiqui N, Sykes P, Westermann AM, Seddon B (2014) Gynecologic Cancer InterGroup (GCIG) consensus review for endometrial stromal sarcoma. Int J Gynecol Cancer 24:S67–S72. https://doi.org/10.1097/IGC.0000000000000205 CrossRefPubMed

Balleine RL, Earls PJ, Webster LR, Mote PA, deFazio A, Harnett PR, Clarke CL (2004) Expression of progesterone receptor a and B isoforms in low-grade endometrial stromal sarcoma. Int J Gynecol Pathol 23:138–144CrossRefPubMed

Brooks SE, Zhan M, Cote T, Baquet CR (2004) Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol Oncol 93:204–208. https://doi.org/10.1016/j.ygyno.2003.12.029 CrossRefPubMed

Brys M, Semczuk A, Baranowski W, Jakowicki J, Krajewska WM (2002) Androgen receptor (AR) expression in normal and cancerous human endometrial tissues detected by RT-PCR and immunohistochemistry. Anticancer Res 22:1025–1031PubMed

Burke C, Hickey K (2004) Treatment of endometrial stromal sarcoma with a gonadotropin-releasing hormone analogue. Obstet Gynecol 104:1182–1184. https://doi.org/10.1097/01.AOG.0000133533.05148.aa CrossRefPubMed

Cade TJ, Quinn MA, Rome RM, Polyakov A (2014) Prognostic significance of steroid receptor positivity and adjuvant progestogen use in endometrial stromal sarcoma. Aust N Z J Obstet Gynaecol 54:453–456. https://doi.org/10.1111/ajo.12245 CrossRefPubMed

Castoria G, Giovannelli P, Di Donato M, Hayashi R, Arra C, Appella E, Auricchio F, Migliaccio A (2013) Targeting androgen receptor/Src complex impairs the aggressive phenotype of human fibrosarcoma cells. PLoS One 8:e76899. https://doi.org/10.1371/journal.pone.0076899 CrossRefPubMedPubMedCentral

10.

Castoria G, Giovannelli P, Di Donato M, Ciociola A, Hayashi R, Bernal F, Appella E, Auricchio F, Migliaccio A (2014) Role of non-genomic androgen signalling in suppressing proliferation of fibroblasts and fibrosarcoma cells. Cell Death Dis 5:e1548. https://doi.org/10.1038/cddis.2014.497 CrossRefPubMedPubMedCentral

11.

Chang KL, Crabtree GS, Lim-Tan SK, Kempson RL, Hendrickson MR (1990) Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. Am J Surg Pathol 14:415–438CrossRefPubMed

12.

Dupont NC, Disaia PJ (2010) Recurrent endometrial stromal sarcoma: treatment with a progestin and gonadotropin releasing hormone agonist. Sarcoma 2010:353679. https://doi.org/10.1155/2010/353679 CrossRefPubMedPubMedCentral

13.

Ingram DR, Dillon LM, Lev DC, Lazar A, Demicco EG, Eisenberg BL, Miller TW (2014) Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma. BMC Clin Pathol 14:42. https://doi.org/10.1186/1472-6890-14-42 CrossRefPubMedPubMedCentral

14.

Koivisto-Korander R, Butzow R, Koivisto AM, Leminen A (2011) Immunohistochemical studies on uterine carcinosarcoma, leiomyosarcoma, and endometrial stromal sarcoma: expression and prognostic importance of ten different markers. Tumour Biol 32:451–459. https://doi.org/10.1007/s13277-010-0138-1 CrossRefPubMed

15.

Leunen M, Breugelmans M, De Sutter P, Bourgain C, Amy JJ (2004) Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor letrozole. Gynecol Oncol 95:769–771. https://doi.org/10.1016/j.ygyno.2004.07.063 CrossRefPubMed

16.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262 CrossRefPubMed

17.

Maluf FC, Sabbatini P, Schwartz L, Xia J, Aghajanian C (2001) Endometrial stromal sarcoma: objective response to letrozole. Gynecol Oncol 82:384–388. https://doi.org/10.1006/gyno.2001.6238 CrossRefPubMed

18.

Mesia AF, Demopoulos RI (2000) Effects of leuprolide acetate on low-grade endometrial stromal sarcoma. Am J Obstet Gynecol 182:1140–1141CrossRefPubMed

19.

Moinfar F, Regitnig P, Tabrizi AD, Denk H, Tavassoli FA (2004) Expression of androgen receptors in benign and malignant endometrial stromal neoplasms. Virchows Arch 444:410–414. https://doi.org/10.1007/s00428-004-0981-9 CrossRefPubMed

20.

Nam JH (2011) Surgical treatment of uterine sarcoma. Best Pract Res Clin Obstet Gynaecol 25:751–760. https://doi.org/10.1016/j.bpobgyn.2011.05.009 CrossRefPubMed

21.

Nam JH, Park JY (2010) Update on treatment of uterine sarcoma. Curr Opin Obstet Gynecol 22:36–42. https://doi.org/10.1097/GCO.0b013e328334d90f CrossRefPubMed

22.

Rauh-Hain JA, del Carmen MG (2013) Endometrial stromal sarcoma: a systematic review. Obstet Gynecol 122:676–683. https://doi.org/10.1097/AOG.0b013e3182a189ac CrossRefPubMed

23.

Reich O, Regauer S (2004) Aromatase expression in low-grade endometrial stromal sarcomas: an immunohistochemical study. Mod Pathol 17:104–108. https://doi.org/10.1038/sj.modpathol.3800031 CrossRefPubMed

24.

Reich O, Regauer S, Urdl W, Lahousen M, Winter R (2000) Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas. Br J Cancer 82:1030–1034. https://doi.org/10.1054/bjoc.1999.1038 CrossRefPubMedPubMedCentral

25.

Reich O, Nogales FF, Regauer S (2005) Gonadotropin-releasing hormone receptor expression in endometrial stromal sarcomas: an immunohistochemical study. Mod Pathol 18:573–576. https://doi.org/10.1038/modpathol.3800325 CrossRefPubMed

26.

Ryu H, Choi YS, Song IC, Yun HJ, Jo DY, Kim S, Lee HJ (2015) Long-term treatment of residual or recurrent low-grade endometrial stromal sarcoma with aromatase inhibitors: a report of two cases and a review of the literature. Oncol Lett 10:3310–3314. https://doi.org/10.3892/ol.2015.3674 CrossRefPubMedPubMedCentral

27.

Scribner DR Jr, Walker JL (1998) Low-grade endometrial stromal sarcoma preoperative treatment with depo-Lupron and Megace. Gynecol Oncol 71:458–460. https://doi.org/10.1006/gyno.1998.5174 CrossRefPubMed

28.

Shah JP, Bryant CS, Kumar S, Ali-Fehmi R, Malone JM Jr, Morris RT (2008) Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 112:1102–1108. https://doi.org/10.1097/AOG.0b013e31818aa89a CrossRefPubMed

29.

Shoji K, Oda K, Nakagawa S, Kawana K, Yasugi T, Ikeda Y, Takazawa Y, Kozuma S, Taketani Y (2011) Aromatase inhibitor anastrozole as a second-line hormonal treatment to a recurrent low-grade endometrial stromal sarcoma: a case report. Med Oncol 28:771–774. https://doi.org/10.1007/s12032-010-9511-6 CrossRefPubMed

30.

Sommeijer DW, Sjoquist KM, Friedlander M (2013) Hormonal treatment in recurrent and metastatic gynaecological cancers: a review of the current literature. Curr Oncol Rep 15:541–548. https://doi.org/10.1007/s11912-013-0343-3 CrossRefPubMed

31.

Thanopoulou E, Aleksic A, Thway K, Khabra K, Judson I (2015) Hormonal treatments in metastatic endometrial stromal sarcomas: the 10-year experience of the sarcoma unit of Royal Marsden Hospital. Clin Sarcoma Res 5:8. https://doi.org/10.1186/s13569-015-0024-0 CrossRefPubMedPubMedCentral

32.

Toro JR, Travis LB, Wu HJ, Zhu K, Fletcher CD, Devesa SS (2006) Incidence patterns of soft tissue sarcomas, regardless of primary site, in the surveillance, epidemiology and end results program, 1978-2001: an analysis of 26,758 cases. Int J Cancer 119:2922–2930. https://doi.org/10.1002/ijc.22239 CrossRefPubMed

33.

Wade K, Quinn MA, Hammond I, Williams K, Cauchi M (1990) Uterine sarcoma: steroid receptors and response to hormonal therapy. Gynecol Oncol 39:364–367CrossRefPubMed

34.

Wagle S, Park SH, Kim KM, Moon YJ, Bae JS, Kwon KS, Park HS, Lee H, Moon WS, Kim JR, Jang KY (2015) DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma. Sci Rep 5:13144. https://doi.org/10.1038/srep13144 CrossRefPubMedPubMedCentral

35.

Yamaguchi M, Erdenebaatar C, Saito F, Motohara T, Miyahara Y, Tashiro H, Katabuchi H (2015) Long-term outcome of aromatase inhibitor therapy with Letrozole in patients with advanced low-grade endometrial stromal sarcoma. Int J Gynecol Cancer 25:1645–1651. https://doi.org/10.1097/IGC.0000000000000557 CrossRefPubMed

Title: Investigation of hormone receptor expression and its prognostic value in endometrial stromal sarcoma
Authors: Jeong-Yeol Park
Min-Hyun Baek
Yangsoon Park
Young-Tak Kim
Joo-Hyun Nam
Publication date: 01-07-2018
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 1/2018
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-018-2358-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Investigation of hormone receptor expression and its prognostic value in endometrial stromal sarcoma

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Book Review—Diagnostic pathology: blood and bone marrow, 2nd edition

Pathology of idiopathic non-cirrhotic portal hypertension

Non-sebaceous lymphadenoma of the lacrimal gland: first report of a new localization

Predominantly cystic clear cell renal cell carcinoma and multilocular cystic renal neoplasm of low malignant potential form a low-grade spectrum

Vascular liver diseases on the clinical side: definitions and diagnosis, new concepts

Hepatocellular nodules in vascular liver diseases