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Full lenght article| Volume 210, P64-68, March 2017

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Immunohistochemical expression pattern of metastasis suppressor KISS-1 protein in adenomyosis lesions and normal endometrium

Published:December 05, 2016DOI:https://doi.org/10.1016/j.ejogrb.2016.12.004

      Abstract

      Objective

      Kisspeptins are multifunctional peptides; it has been shown that they act as inhibitors of tumor metastasis in a range of cancers and that they are also involved in cell invasion through regulation of matrix metalloproteinases (MMPs). The aim of this study was to investigate the expression of KISS-1 protein in adenomyosis lesions compared with matched eutopic endometrium, as well as with endometrium from patients without adenomyosis.

      Study Design

      In this comparative, non-interventional study, adenomyosis and corresponding eutopic endometrium samples from women with histologically proven adenomyosis after hysterectomy, and eutopic endometrium samples from women without adenomyosis were analysed. Expression of KISS-1 protein was analyzed immunohistochemically in formalin-fixed, paraffin-embedded adenomyotic tissue specimens (n = 29), matched eutopic endometrium from the same patients (n = 29) and normal endometrium from patients without adenomyosis (n = 29).

      Results

      Using a semi-quantitative immunohistochemical score, we found that KISS-1 protein expression was higher in the adenomyotic as compared with matched eutopic glandular endometrium (p < 0.05), in which in turn KISS-1 protein expression was higher than those from patients without adenomyosis (p < 0.001). The inverse correlation was found in the stroma, between adenomyosis lesions and matched eutopic endometrium (p < 0.01), while no statistically significant correlation was found in KISS-1 protein expression in the stroma between patients with and without adenomyosis.

      Conclusions

      KISS-1 protein expression appears to be up-regulated in adenomyotic as compared with eutopic glandular endometrium of patients with, as well as women without adenomyosis. These findings are suggestive of the involvement of KISS-1 protein in the pathogenesis and maintenance of adenomyosis. Future studies should investigate whether KISS1 protein could be used as a marker for early and minimally invasive detection of adenomyosis, based on its differential protein expression pattern in the eutopic endometrium of patients with and without adenomyosis.

      Keywords

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      References

        • Azziz R.
        Adenomyosis: Current perspectives.
        Obstet Gynecol Clin North Am. 1989; 16: 221-235
        • Emge L.A.
        The elusive adenomyosis of the uterus: its historical past and its present state of recognition.
        Am J Obstet Gynecol. 1962; 83: 1541-1563
        • Ferenczy A.
        Pathophysiology of adenomyosis.
        Hum Reprod Update. 1998; 4: 312
        • Levgur M.
        • Abadi M.A.
        • Tucker A.
        Adenomyosis: symptoms, histology, and pregnancy terminations.
        Obstet Gynecol. 2000; 95: 688
        • Jin H.Y.
        • Zhou L.S.
        Ultrastructural change of the ectopic endometrium and its significance in endometriosis.
        Nan Fang Yi Ke Da Xue Xue Bao. 2010; 30: 1318-1320
        • Matsuda M.
        • Sasabe H.
        • Adachi Y.
        • Suzuki T.
        • Mori T.
        Increased invasion activity of endometrial stromal cells and elevated expression of matrix metalloproteinase messenger RNA in the uterine tissues of mice with experimentally induced adenomyosis.
        Am J Obstet Gynecol. 2001; 185: 1374-1380
        • Mehasseb M.K.
        • Bell S.C.
        • Habiba M.A.
        The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse.
        Reproduction. 2009; 138: 341-350
        • Mori S.
        • Fujii M.
        • Kudo R.
        Expression of the small molecular weight matrix metalloproteinase in ademyosis of the mouse uterus.
        Acta Obstet Gynecol Jpn. 1996; 48: 386-392
        • Lee J.H.
        • Miele M.E.
        • Hicks D.J.
        • et al.
        KiSS-1, a novel human malignant melanoma metastasis suppressor gene.
        J Natl Cancer Inst. 1996; 88: 1731-1737
        • Mead E.J.
        • Maguire J.J.
        • Kuc R.E.
        • Davenport A.P.
        Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system.
        Br J Pharmacol. 2007; 151: 1143-1153
        • Yan C.
        • Wang H.
        • Boyd D.D.
        KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha-induced block of p65/p50 nuclear translocation.
        J Biol Chem. 2001; 276: 1164-1172
        • Bilban M.
        • Ghaffari-Tabrizi N.
        • Hintermann E.
        • et al.
        Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts.
        J Cell Sci. 2004; 117: 1319-1328
        • Qiao C.
        • Wang C.H.
        • Shang T.
        • Lin Q.D.
        Clinical significance of KiSS-1 and matrix metalloproteinase-9 expression in trophoblasts of women with preeclampsia and their relation to perinatal outcome of neonates.
        Zhonghua Fu Chan Ke Za Zhi. 2005; 40: 585-590
        • Timologou A.
        • Zafrakas M.
        • Grimbizis G.
        • Miliaras D.
        • Kotronis K.
        • Stamatopoulos P.
        • et al.
        Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium.
        Eur J Obstet Gynecol Reprod Biol. 2016; 199: 110-115
        • Naftalin J.
        • Hoo W.
        • Pateman K.
        • Mavrelos D.
        • Holland T.
        • Jurkovic D.
        How common is adenomyosis: a prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic.
        Hum Reprod. 2012; 27: 3432-3439
        • Remmele W.
        • Stegner H.E.
        [Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue].
        Pathologe. 1987; 8: 138-140
        • van Diest P.J.
        • van Dam P.
        • Henzen-Logmans S.C.
        • Berns E.
        • van der Burg M.E.
        • Green J.
        • et al.
        A scoring system for immunohistochemical staining: consensus report of the task force for basic research of the EORTC-GCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group.
        J Clin Pathol. 1997; 50: 801-804
        • Sofic A.
        • Husic-Selimovic A.
        • Carovac A.
        • Jahic E.
        • Smailbegovic V.
        • Kupusovic J.
        The Significance of MRI Evaluation of the Uterine Junctional Zone in the Early Diagnosis of Adenomyosis.
        Acta Inform Med. 2016; 24: 103-106
        • Verma S.K.
        • Lev-Toaff A.S.
        • Baltarowich O.H.
        • Bergin D.
        • Verma M.
        • Mitchell D.G.
        Adenomyosis: sonohysterography with MRI correlation.
        Am J Roentgenol. 2009; 192: 1112-1116
        • Wise A.
        • Gearing K.
        • Rees S.
        Target validation of G-protein coupled receptors.
        Drug Discov Today. 2002; 7: 235-246
        • Kirby H.R.
        • Maguire J.J.
        • Colledge W.H.
        • Davenport A.P.
        International union of basic and clinical pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function.
        Pharmacol Rev. 2010; 62: 565-578
        • Li L.
        • Liu H.Y.
        • Zhang Y.Q.
        • Zhang H.P.
        • Hou H.L.
        Heparanase and metastin expressions in eutopic endometrial glandular epithelium cells of adenomyosis in vitro and the effect of mifepristone for their expressions and significance.
        Chin J Pract Gyn Obstet. 2009; 25: 674-676