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The Relationship Among HOXA10, Estrogen Receptor α, Progesterone Receptor, and Progesterone Receptor B Proteins in Rectosigmoid Endometriosis: A Tissue Microarray Study

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Abstract

Background

Very few studies have evaluated the expression of homeobox A10 (HOXA10) and steroid (estrogen and progesterone) receptors exclusively in deep endometriosis. Conclusions drawn from studies evaluating peritoneal and ovarian endometriosis are usually generalized to explain the pathogenesis of the disease as a whole. We aimed to evaluate the expression of HOXA10, estrogen receptor α (ER-α), progesterone receptor (PR), and PR-B in rectosigmoid endometriosis (RE), a typical model of deep disease.

Methods

We used RE samples from 18 consecutive patients to construct tissue microarray blocks. Nine patients each were operated during the proliferative and secretory phases of the menstrual cycle. We quantified the expressions of proteins by immunohistochemistry using the modified Allred score.

Result

The HOXA10 was expressed in the stroma of nodules during the secretory phase in 5 of the 18 patients. Expression of ER-α (in 16 of 18 patients), PR (in 17 of 18 patients), and PR-B (17 of 18 patients) was moderate to strong in the glands and stroma of nodules during both phases. Expression of both PR (P = .023) and PR-B (P = .024) was significantly greater during the secretory phase.

Conclusion

The HOXA10 is expressed in RE, where it likely imparts the de novo identity of endometriotic lesions. The ER-α, PR, and PR-B are strongly expressed in RE, which differs from previous studies investigating peritoneal and ovarian lesions. This suggests different routes of pathogenesis for each of the 3 types of endometriosis.

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References

  1. Clement PB. The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol. 2007;14(4):241–260.

    Article  PubMed  Google Scholar 

  2. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–596.

    Article  CAS  PubMed  Google Scholar 

  3. Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update. 1998;4(5): 741–751.

    Article  CAS  PubMed  Google Scholar 

  4. Bianchi PH, Pereira RM, Zanatta A, Alegretti JR, Motta EL, Serafini PC. Extensive excision of deep infiltrative endometriosis before in vitro fertilization significantly improves pregnancy rates. J Minim Invasive Gynecol. 2009;16(2):174–180.

    Article  PubMed  Google Scholar 

  5. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez J. Deep endometriosis: definition, diagnosis, and treatment. Fertil Steril. 2012;98(3):564–571.

    Article  PubMed  Google Scholar 

  6. Noel JC, Chapron C, Bucella D, et al. Estrogen and progesterone receptors in smooth muscle component of deep infiltrating endometriosis. Fertil Steril. 2009;93(6): 1774–1777.

    Article  PubMed  Google Scholar 

  7. Kitano T, Matsumoto T, Takeuchi H, et al. Expression of estrogen and progesterone receptors in smooth muscle metaplasia of rectovaginal endometriosis. Int J Gynecol Pathol. 2007;26(2):124–129.

    Article  PubMed  Google Scholar 

  8. Brandenberger AW, Lebovic DI, Tee MK, et al. Oestrogen receptor (ER)-alpha and ER-beta isoforms in normal endometrial and endometriosis-derived stromal cells. Mol Hum Reprod. 1999; 5(7):651–655.

    Article  CAS  PubMed  Google Scholar 

  9. Attia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. Progesterone receptor isoform A but not B is expressed in endometriosis. J Clin Endocrinol Metab. 2000;85(8):2897–2902.

    CAS  PubMed  Google Scholar 

  10. Wu Y, Strawn E, Basir Z, Halverson G, Guo SW. Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics. 2006;1(2):106–111.

    Article  PubMed  Google Scholar 

  11. Trukhacheva E, Lin Z, Reierstad S, Cheng YH, Milad M, Bulun SE. Estrogen receptor (ER) beta regulates ERalpha expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab. 2009;94(2):615–622.

    Article  CAS  PubMed  Google Scholar 

  12. McGinnis W, Rrumlauf R. Homeobox genes and axial patterning. Cell. 1992;68(2):283–302.

    Article  CAS  PubMed  Google Scholar 

  13. Browne H, Taylor H. HOXA10 expression in ectopic endometrial tissue. Fertil Steril. 2006;85(5): 1386–1390.

    Article  CAS  PubMed  Google Scholar 

  14. van Langendonckt A, Luyckx M, Gonzalez MD, Defrere S, Donnez J, Squifflet J. Differential expression of genes from the homeobox A cluster in deep endometriotic nodules and peritoneal lesions. Fertil Steril. 2010;94(6):1995–2000.

    Article  PubMed  Google Scholar 

  15. Taylor HS, Vanden Heuvel GB, Igarashi P. A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 1997;57(6):1338–1345.

    Article  CAS  PubMed  Google Scholar 

  16. Taylor HS, Arici A, Olive D, Igarashi P. HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998;101(7):1379–1384.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zanatta A, Rocha AM, Carvalho FM, et al. The role of the HoxalO/HOXA10 gene in the etiology of endometriosis and its related infertility: a review. J Assist Reprod Genet. 2010; 27(12):701–710.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Daftary GS, Taylor HS. Endocrine regulation of HOX genes. Endocr Rev. 2006;27(4):331–355.

    Article  CAS  PubMed  Google Scholar 

  19. Watanabe T, Inoue S, Ogawa S, et al. Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. Biochem Biophys Res Com-mun. 1997;236(1):140–145.

    Article  CAS  PubMed  Google Scholar 

  20. McDonnell DP, Goldman ME. RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism. J Biol Chem. 1994;269(16): 11945–11949.

    CAS  PubMed  Google Scholar 

  21. Kulakosky PC, McCarty MA, Jernigan SC, Risinger KE, Klinge CM. Response element sequence modulates estrogen receptor alpha and beta affinity and activity. J Mol Endocrinol. 2002; 29(1):137–152.

    Article  CAS  PubMed  Google Scholar 

  22. Akbas GE, Song J, Taylor HS. A HOXA10 estrogen response element (ERE) is differentially regulated by 17 beta-estradiol and diethylstilbestrol (DES). J Mol Biol. 2004;340(5): 1013–1023.

    Article  CAS  PubMed  Google Scholar 

  23. Couse JF, Dixon D, Yates M, et al. Estrogen receptor-alpha knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract. Dev Biol. 2001;238(2):224–238.

    Article  CAS  PubMed  Google Scholar 

  24. Wu D, Song D, Li X, Yu M, Li C, Zhao S. Molecular characterization and identification of the E2/P4 response element in the porcine HOXA10 gene. Mol Cell Biochem. 2013;374(l–2): 213–222.

    Article  CAS  PubMed  Google Scholar 

  25. Samartzis N, Samartzis EP, Noske A, et al. Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study. Reprod Biol Endocrinol. 2012;10(1):30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3–25.

    Article  Google Scholar 

  27. Kallioniemi OP, Wagner U, Kononen J, Sauter G. Tissue micro-array technology for high-throughput molecular profiling of cancer. Hum Mol Genet. 2001;10(7):657–662.

    Article  CAS  PubMed  Google Scholar 

  28. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998;4(7):844–847.

    Article  CAS  PubMed  Google Scholar 

  29. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11(2):155–168.

    CAS  PubMed  Google Scholar 

  30. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997;67(5):817–821.

  31. Calcagno A, Grassi T, Mariuzzi L, et al. Expression patterns of Aurora A and B kinases, Ki-67 and the estrogen and progesterone receptors determined using an endometriosis tissue microarray model. Hum Reprod. 2011;26(10):2731–2741.

    Article  CAS  PubMed  Google Scholar 

  32. Yu YY, Pan YS, Zhu ZG. Homeobox genes and their functions on development and neoplasm in gastrointestinal tract. Eur J Surg Oncol. 2007;33(2):129–132.

    Article  CAS  PubMed  Google Scholar 

  33. Signorile PG, Baldi F, Bussani R, D’Armiento M, De FM, Baldi A. Ectopic endometrium in human foetuses is a common event and sustains the theory of mullerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer. J Exp Clin Cancer Res. 2009;28:49.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Block K, Kardana A, Igarashi P, Taylor HS. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system. FASEB J. 2000;14(9):1101–1108.

    Article  CAS  PubMed  Google Scholar 

  35. Picchi J, Trombi L, Spugnesi L, et al. HOX and TALE signatures specify human stromal stem cell populations from different sources. J Cell Physiol. 2013;228(4):879–889.

    Article  CAS  PubMed  Google Scholar 

  36. Xue Q, Lin Z, Cheng YH, et al. Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod. 2007;77(4):681–687.

    Article  CAS  PubMed  Google Scholar 

  37. Burns KA, Rodriguez KF, Hewitt SC, Janardhan KS, Young SL, Korach KS. Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model. Endocrinology. 2012;153(8):3960–3971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. McDonnell DP, Shahbaz MM, Vegeto E, Goldman ME. The human progesterone receptor A-form functions as a transcriptional modulator of mineralocorticoid receptor transcriptional activity. J Steroid Biochem Mol Biol. 1994;48(5–6):425–432.

    Article  CAS  PubMed  Google Scholar 

  39. Kamat AA, Younes PS, Sayeeduddin M, Wheeler TM, Simpson JL, Agoulnik AI. Protein expression profiling of endometriosis: validation of 2-mm tissue microarrays. Fertil Steril. 2004;82(6): 1681–1683.

    Article  PubMed  Google Scholar 

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Correspondence to Alysson Zanatta MD, PhD.

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Zanatta, A., Pereira, R.M.A., da Rocha, A.M. et al. The Relationship Among HOXA10, Estrogen Receptor α, Progesterone Receptor, and Progesterone Receptor B Proteins in Rectosigmoid Endometriosis: A Tissue Microarray Study. Reprod. Sci. 22, 31–37 (2015). https://doi.org/10.1177/1933719114549846

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