Expression of Jun activation domain-binding protein 1 and p27 Kip1 in endometrial polyps and uterine leiomyomas

Aim: The expression, localization, and density of Jab1 and p27 in endometrial polyps and uterine leiomyomas and the associations between these diseases and Jab1 and p27 based on clinical outcomes were explored. Materials and Methods: Tissues from 28 patients (14 with endometrial polyps and 14 with uterine leiomyomas) were used to investigate the expression of Jab1 and p27 by immunohistochemical analysis from November 2011 to April 2014. Results: Jab1 exhibited positive immunoreactivity: 78.5% in the endometrial polyp group in glandular epithelial cells and 71.4% in the uterine leiomyoma group in smooth muscle cells. In contrast to Jab1, p27 exhibited negative immunoreactivity: 76.9% in the endometrial polyp group and 78.6% in the uterine leiomyoma group. The lesions were larger in cases of expressed Jab1 only, rather than in cases with positive or negative expression of both proteins. Tissues that were recurrent did not express p27. Conclusions: Jab1 was expressed in the glandular epithelium of endometrial polyps and stromal layer of uterine leiomyomas, while p27 was suppressed in both diseases. Positive expression of Jab1 and negative expression of p27 were related to lesion growth.

Endometrium; Jab1; Leiomyoma; Polyps; Proteins; Uterus.

[1] Unal B., Dogan S., Karaveli F.S., Simsek T., Erdogan G., Candaner I.: “Giant endometrial polyp in a postmenopausal woman without hormone/drug use and vaginal bleeding”. Case Rep. Obstet. Gynecol., 2014, 2014, 518398.

[2] Jeong E.H., Hong G.Y., Kim B.R., Park S.N., Lee H.H., Na Y.J., et al.: “The relationship between uterine myoma growth and the endocrine disruptor in postmenopausal women”. J. Menopausal. Med., 2013, 19, 130.

[3] Usubutun A., Mutter G.L., Saglam A., Dolgun A., Ozkan E.A., Ince T., et al.: “Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists”. Modern Pathol., 2012, 25, 877.

[4] Kim T.H., Lee H.H.: “Uterine leiomyoma research”. Kosin. Med. J., 2015, 30, 13.

[5] Lin C.Y., Ding H.J., Chen Y.K., Liu C.S., Lin C.C., Kao C.H.: “F-18 FDG PET in detecting uterine leiomyoma”. Clinical Imaging, 2008, 32, 38.

[6] Onalan R., Onalan G., Tonguc E., Ozdener T., Dogan M., Mollamahmutoglu L.: “Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization”. Fertil. Steril., 2009, 91, 1056.

[7] Asano R., Asai-Sato M., Miyagi Y., Mizushima T., Koyama-Sato M., Nagashima Y., et al.: “Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth”. Am. J. Obstet. Gynecol., 2015, 199, e1.

[8] Lieng M., Istre O., Sandvik L., Qvigstad E.: “Prevalence, 1-year regression rate, and clinical significance of asymptomatic endometrial polyps: cross-sectional study”. J. Minim. Invasive. Gynecol., 2009, 16, 465.

[9] Darji P., Banker H., Gandhi V., Thakkar G.: “Postmenopausal woman with vaginal mass: do not forget to see for uterine inversion”. BMJ Case. Rep.. 2012, doi: 10.1136/bcr-02-2012-5841.

[10] Porrello E., Rivellini C., Dina G., Triolo D., Del Carro U., Ungaro D., et al.: “Jab1 regulates Schwann cell proliferation and axonal sorting through p27”. J. Exp. Med., 2014, 211, 29.

[11] Lee W.S., Park E.S., Kim D.H., Kim T.H., Lee H.H., Chung S.H.: “Expression of p53, p27 and Jab1 protein in epithelial ovarian tumors”. Eur. J. Gynaecol. Oncol., 2012, 33, 358.

[12] Kim T.H., Lee H.H., Chung S.H., Park J., Lee A.: “Expression of p27 and Jun activation domain-binding protein 1 in endometriosis”. Arch. Gynecol. Obstet., 2015, 292, 377.

[13] Antunes A., Vassallo J., Pinheiro A., Leão R., Pinto Neto A.M., Costa-Paiva L.: “Immunohistochemical expression of estrogen and progesterone receptors in endometrial polyps: a comparison between benign and malignant polyps in postmenopausal patients”. Oncol. Lett., 2014, 7, 1944.

[14] Kim J.J., Kurita T., Bulun S.E.: “Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer”. Endocr. Rev., 2013, 34, 130.

[15] Gao X., Yu L., Castro L., Tucker C.J., Moore A.B., Xiao H., et al.: “An essential role of p27 downregulation in fenvalerate-induced cell growth in human uterine leiomyoma and smooth muscle cells”. Am. J. Physiol. Endocrinol. Metab., 2012, 303, E1025.

[16] Shiozawa T., Horiuchi A., Kato K., Obinata M., Konishi I., Fujii S., et al.: “Up-regulation of p27Kip1 by progestins is involved in the growth suppression of the normal and malignant human endometrial glandular cells”. Endocrinol., 2001, 142, 4182.

[17] Lahav-Baratz S., Ben-Izhak O., Sabo E., Ben-Eliezer S., Lavie O., Ishai D., et al.: “Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium”. Mol. Hum. Reprod., 2004, 10, 567.

[18] Pei C.P., Osman M., Dusa N.M.: “Loss of p27 Kip1 expression in high grade human prostate adenocarcinoma”. J. Biosci. Biotechnol., 2014, 3, 119.

[19] Vu T.T., Shackleford T., Zhang Q., Oh D.Y., Fuling Z., Pan Y., et al.: “Jab1/Csn5 as a novel driver for therapeutic resistance in HER2-positive breast cancer”. Cancer. Res., 2012, 72, 1912.

[20] Masciullo V., Susini T., Zamparelli A., Bovicelli A., Minimo C., Massi D., et al.: “Frequent loss of expression of the cyclin-dependent kinase inhibitor p27Kip1 in estrogen-related endometrial adenocarcinomas”. Clin. Cancer. Res., 2003, 9, 5332.

[21] Shackleford T.J., Claret F.X.: “JAB1/CSN5: a new player in cell cycle control and cancer”. Cell. Div., 2010, 5, 26.

[22] Ramachandran S., Kwon K.Y., Shin S.J., Kwon S.H., Cha S.D., Bae I., et al.: “Cyclin-dependent kinase inhibitor p27Kip1 controls growth and cell cycle progression in human uterine leiomyoma”. J. Korean. Med. Sci., 2008, 23, 667.

[23] Zola F.E., Nogueira A.A., de Andrade J.M., dos Reis F.J.C.: “Hysteroscopic appearance of malignant and benign endometrial lesions: a case–control study”. Arch. Gynecol. Obstet., 2007, 275, 49.

[24] Mills A.M., Ly A., Balzer B.L., Hendrickson M.R., Kempson R.L., McKenney J.K., et al.: “Cell cycle regulatory markers in uterine atypical leiomyoma and leiomyosarcoma: immunohistochemical study of 68 cases with clinical follow-up”. Am. J. Surg. Pathol., 2013, 37, 634.