THE ROLE OF BETA-CATENIN AND FOXP1 IN THE PATHOGENESIS OF POLYPOID ENDOMETRIOSIS

Year 2024, Volume: 87 Issue: 1, 54 - 60, 29.01.2024

Ali Yılmaz Altay , Ekrem Yavuz , Aysel Bayram , Cenk Yaşa , Hamdullah Sözen , Semen Önder

https://doi.org/10.26650/IUITFD.1292132

Abstract

Objective: To investigate whether beta catenin and Forkhead box protein P1 (FOXP1) play a role in pathogenesis of polypoid endometriosis (PE).
Material and Method: Our study included fifteen cases of PE. Clinical findings were gathered from archived files of relevant clinics and pathology reports. All glass slides were re-examined for confirmation of the diagnosis and the detection of additional microscopic findings. An immunohistochemical examination was performed using anti beta catenin and FOXP1 antibodies in fifteen cases of PE, and in a control group that contained nine cases of endometrial polyps (EP) and nine cases of conventional ovarian endometriosis (OE).
Result: Stromal nuclear beta catenin expression was observed in six cases in PE, five cases in EP and one case in the OE group. Stromal FOXP1 staining in PE and EP was significantly reduced as compared to OE. Five PE and two EP cases showed stromal FOXP1 staining while all the OE cases showed stromal FOXP1 staining. The Stromal FOXP1 staining was statistically significant between PE vs OE (p=0.002) and EP vs OE (p=0.023) cases. There was no difference between PE and the control cases in terms of nuclear beta catenin staining (p=0.69). There was no correlation between these two antibodies and histologic features.
Conclusion: The loss of stromal FOXP1 is another biological difference of PE and the overall similarity of expression of FOXP1between PE and EP could be regarded as a contributing factor for polyp formation.

Keywords

Endometriosis, polyp, immunohistochemistry, FOXP1, beta-catenin

Project Number

yok

POLİPOİD ENDOMETRİOZİS PATOGENEZİNDE BETA-KATENİN VE FOXP1’İN ROLÜ

Abstract

Amaç: Polipoid endometriozis (PE) patogenezinde Forkhead box protein P1 (FOXP1) ve beta-katenin’nin rolünün araştırılması.
Gereç ve Yöntem: Çalışmaya 15 PE olgusu dahil edilmiştir. Klinik bilgiler hastaların tıbbi kayıtlarından ve patoloji raporlarından elde edilmiştir. Tüm mikroskopik preperatlar tanının doğrulanması ve ek mikroskopik özelliklerin tanımlanması amacıyla tekrar değerlendirilmiştir. FOXP1 ve beta-katenin antikorları kullanılarak 15 PE ve kontrol grubu olarak dokuz endometrial polip (EP) ve dokuz ovarian endometriozis (OE) olgusuna immünhistokimyasal inceleme yapılmıştır.
Bulgular: Stromal nükleer beta-katenin boyanması altı PE, beş EP ve bir OE olgusunda gözlenmiştir. Stromal FOXP1 boyanması OE olgularına göre PE ve EP olgularında belirgin şekilde azalmış olup tüm OE olgularında stromal FOXP1 boyanması izlenirken beş PE ve iki EP olgusunda stromal FOXP1 boyanması saptanmıştır. PE ile OE ve EP ile OE olguları arasındaki stromal FOXP1 boyanması farkı anlamlıdır (sırasıyla p=0,002 ve p=0,023). Beta-katenin ile PE ve kontrol grubu olguları arasında anlamlı fark bulunmamıştır (p=0,69). Histolojik özelliklerle bu antikorların pozitifliği arasında ilişki yoktur.
Sonuç: PE olgularındaki FOXP1 kaybı PE ve konvansiyonel endometriosis arasındaki bir diğer biyolojik fark olarak tanımlanabilir. Ayrıca PE ve EP olgularındaki stromal FOXP1 boyanmasındaki benzerlik FOXP1’in polip oluşumunda rolü olduğunu düşündürmektedir.

Keywords

Endometriozis, polip, immünhistokimya, FOXP1, beta-katenin

Supporting Institution

yok

Project Number

yok

References

• Olive DL, Schwartz LB. Endometriosis. N Engl J Med 1993;328(24):1759-69. [CrossRef] google scholar
• Wellbery C. Diagnosis and treatment of endometriosis. Am Fam Physician 1999;60(6):1753-62, 1767-8. Erratum in: Am Fam Physician 2000;61(9):2614. google scholar
• Mostoufizadeh M, Scully RE. Malignant tumors arising in endometriosis. Clin Obstet Gynecol 1980 ;23(3):951-63. [CrossRef] google scholar
• Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O’Hanlon D, Sung HK, et al. An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell 2011;147(1):132-46. [CrossRef] google scholar
• Walker MP, Stopford CM, Cederlund M, Fang F, Jahn C, Rabinowitz AD, et al. FOXP1 potentiates Wnt/β-catenin signaling in diffuse large B cell lymphoma. Sci Signal 2015;8(362):ra12. [CrossRef] google scholar
• Willert K, Nusse R. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev 1998;8(1):95-102. [CrossRef] google scholar
• Shao X, Wei X. FOXP1 enhances fibrosis via activating Wnt/ β-catenin signaling pathway in endometriosis. Am J Transl Res 2018;10(11):3610-8. google scholar
• Klemmt PAB, Starzinski-Powitz A. Molecular and Cellular Pathogenesis of Endometriosis. Curr Womens Health Rev 2018;14(2):106-16. [CrossRef] google scholar
• Parker RL, Dadmanesh F, Young RH, Clement PB. Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature. Am J Surg Pathol 2004;28(3):285- 97. [CrossRef] google scholar
• Jiang W, Roma AA, Lai K, Carver P, Xiao SY, Liu X. Endometriosis involving the mucosa of the intestinal tract: a clinicopathologic study of 15 cases. Mod Pathol 2013;26(9):1270-8. [CrossRef] google scholar
• Altay AY, Yavuz E, Bayram A, Yasa C, Akhan SE, Topuz S, Onder S. Loss of stromal CD73 expression plays a role in pathogenesis of polypoid endometriosis. Arch Gynecol Obstet 2021;303(6):1523-30. [CrossRef] google scholar
• Xiong W, Zhang L, Yu L, Xie W, Man Y, Xiong Y, et al. Estradiol promotes cells invasion by activating β-catenin signaling pathway in endometriosis. Reproduction 2015;150(6):507- 16. [CrossRef] google scholar
• Zhang L, Xiong W, Xiong Y, Liu H, Liu Y. 17 β-Estradiol promotes vascular endothelial growth factor expression via the Wnt/β-catenin pathway during the pathogenesis of endometriosis. Mol Hum Reprod 2016;22(7):526-35. [CrossRef] google scholar
• de Mattos RM, Pereira PR, Barros EG, da Silva JH, Palmero CY, da Costa NM, et al. Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis. Histol Histopathol 2016;31(8):933-42. google scholar
• Gaetje R, Holtrich U, Karn T, Cikrit E, Engels K, Rody A, Kaufmann M. Characterization of WNT7A expression in human endometrium and endometriotic lesions. Fertil Steril 2007;88(6):1534-40. [CrossRef] google scholar
• Shang S, Hua F, Hu ZW. The regulation of β-catenin activity and function in cancer: therapeutic opportunities. Oncotarget 2017;8(20):33972-89. [CrossRef] google scholar
• Feng M, Zhang T, Ma H. Progesterone ameliorates the endometrial polyp by modulating the signaling pathway of Wnt and β-catenin via regulating the expression of H19 and miR-152. J Cell Biochem 2019;120(6):10164-74. [CrossRef] google scholar
• Kim JH, Hwang J, Jung JH, Lee HJ, Lee DY, Kim SH. Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression. Mol Cancer 2019;18(1):180. [CrossRef] google scholar
• Cui L, Chen S, Wang D, Yang Q. LINC01116 promotes proliferation and migration of endometrial stromal cells by targeting FOXP1 via sponging miR-9-5p in endometriosis. J Cell Mol Med 2021;25(4):2000-12. [CrossRef] google scholar
• Giatromanolaki A, Koukourakis MI, Sivridis E, Gatter KC, Harris AL, Banham AH. Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression. Mod Pathol 2006;19(1):9-16. [CrossRef] google scholar
• Mizunuma M, Yokoyama Y, Futagami M, Horie K, Watanabe J, Mizunuma H. FOXP1 forkhead transcription factor is associated with the pathogenesis of endometrial cancer. Heliyon 2016;2(5):e00116. [CrossRef] google scholar