Immunohistochemical expression of SNAIL and SLUG in endometrioid endometrial cancer and precursor lesions
DOI:
https://doi.org/10.18203/2320-1770.ijrcog20240458Keywords:
Immunohistochemistry, Endometroid endometrial carcinoma, Endometrial hyperplasia, Slug, SnailAbstract
Background: Endometrioid endometrial carcinoma is one of the most prevalent gynecologic cancers. The epithelial-mesenchymal transition is a multistep process involved in the development of cells that results in disappearance of intercellular adhesion in the epithelium and acquiring mesenchymal properties, hence influence cancer progression and metastasis. Loss of intercellular adhesion can be activated by different mechanisms, including transcriptional repression. However, the expression of transcriptional repressors in EEC and precursor lesions remain to be investigated. In the present study, we evaluated the immunohistochemical expression of proteins of transcriptional after repression snail and slug in EEC and its precursor lesions.
Methods: It was a prospective nested case-control study on women from 35 to 70 years of age. Endometrial biopsies were obtained and processed for routine histological diagnosis. Immunohistochemical expression of snail and slug were evaluated.
Results: A total of 39 EEC cases, 37 Endometrial hyperplasia and 19 normal controls were included in this study. Expression of snail was positive in 77% (30/39) and slug in 82% (32/39) of EEC cases while in precancer group snail was positive in 76% (28/37) and slug in 68% (25/37). In normal control snail was positive in 32% (6/19) and SLUG in 21% (4/19).
Conclusion: Up-regulation of snail & slug observed in both precancer and cancer cases, suggesting their involvement from an early stage of carcinogenesis. Therefore therapies targeted at transcriptional repressors at an early stage of carcinogenesis, i.e., at precancerous lesions, could play a valuable role in reducing cancer progression and metastasis.
References
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
Prat J. Prognostic parameters of endometrial carcinoma. Hum Pathol. 2004;35:649-62.
Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16:8-13.
Fujimoto T. Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. Gynecol Oncol. 2009;112:342-7.
Kechagioglou P, Papi RM, Provatopoulou X, Kalogera E, Papadimitriou E, Grigoropoulos P, et al. Tumor suppressor PTEN in breast cancer: Heterozygosity, mutation and protein expression. Anticancer Res. 2014;34:1387-400.
Sarmadi S, Izadi-Mood N, Sotoudeh K, Tavanger SM. Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium. Diagnos Pathol. 2009;4:41.
Di Cristofano A, Pandolfi PP. The multiple roles of PTEN in tumor suppression. Cell. 2000;100:387-90.
Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92:924-30.
Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9:265-73.
Shih HC, Shiozawa T, Miyamoto T, Kashima H, Feng YZ, Kurai M, et al. Immunohistochemical expression of E-Cadherin beta-catenin in normal and malignant human endometrium: an inverse correlation between E-cadherin and nuclear beta-catenin expression. Anticancer Res. 2004;24:3843-50.
Montserrat N, Mozos A, Llobet D, Dolcet X, Pons C, Herreros AG, et al. Epithelial to mesenchymal transition in early stage endometrioid endometrial carcinoma. Hum Pathol. 2012;43:632-43.
Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanism, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75-90.
Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, et al. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010;101:293-9.
Female Genital Tumours. Available at: https://www. iarc.who.int/. Accessed on 20 November 2023.
Nayak S, Goel MM, Makker A, Bhatia V, Chandra S, Kumar S, et al. Fibroblast Growth Factor (FGF-2) and its receptors FGFR-2 and FGFR-3 May Be Putative Biomarkers of Malignant Transformation of Potentially Malignant Oral Lesions into Oral Squamous Cell Carcinoma. PLoS One. 2015;10:e0138801.
Sadlecki P, Jozwicki J, Antosik P, Sadlecka MW. Expression of selected epithelial-mesenchymal transition transcription factors in Endometrial cancer. Biomed Res Int. 2020;2020:4584250.
Supernat A, Lapinska-Szumczyk S, Majewska H, Gulczynski J, Biernat W, Wydra D, et al. Epithelial-mesenchymal Transition and Cancer Stem Cells in Endometrial Cancer. Anticancer Res. 2013;33:5461-70.
Zhu Q, Tang M, Wu L. Expression of combined interference of SLUG and FoxC2 in endometrial carcinoma and its clinicopathological relationship. Transl Cancer Res. 2020;9(9):5268-80.
Mishra P, Senthivinayagam S, Rana A, Rana B. Glycogen synthase kinase-3β regulates SNAIL and β-catenin during gastrin-induced migration of gastric cancer cells. J mol Signal. 2010;5:9.
Lengrand J, Pastushenko L, Vanuytven S, Song Y, Venet D, Sarate RM, et al. Pharmacological targeting of netrin-1 inhibits EMT in cancer. Nature. 2023;620(7973):402-8.
