Immunohistochemical expression of Stem Cell Marker, Sex-Determining Region Y-Box2 (SOX2) in Endometrial Carcinoma

(Aya Magdy Elyamany , Hala Khedr , Ghada Amr Elshafei and Ahmed Naeem Eesa)

---

Abstract

Sex-determining region Y-box 2 (SOX2), a member of the SOX family, plays a critical role in the regulation of cancerous stem cells. SOX2 can affect embryonic stem cells' capacity for self-renewal and pluripotency. The aim of this study is to assess SOX2 expression and correlation of this expression with different pathological variables in endometrial carcinoma. For 85 endometrial cancer cases that underwent total hysterectomy with bilateral salpingo-oophorectomy, immunohistochemical staining for SOX2 was done. In tumor cells, SOX-2 expression was evaluated. SOX2 expression was detected in 18% of cases, of which undifferentiated and serous endometrial carcinoma showed the highest expression and showed statistically significant relation with high grade, high FIGO stage, high pathological (T) stage, cervical, adnexal and/or serosal, parametrial and/or vaginal involvement, nodal metastasis, lymphovascular space invasion (LVSI), omental tumor deposits and advanced metastatic risk tumor, according to ESGO-ESTRO-ESP system for risk stratification (P value 0.045, 0.011, 0.024, 0.012, 0.004, 0.003, 0.013, 0.032, 0.031 and 0.021), respectively. SOX2 expression was related to high-risk endometrial carcinomas with poor clinicopathological parameters. Thus, SOX2 may be considered as a potential marker for poor prognosis and could be useful in identifying cases that require closer follow-up and aggressive treatment.
KEYWORDS
Tumor grade, tumor stage, oncogenic marker, stem cells, tumor progression, tumor risk

PDF

References

Alshahrani, S., Hablas, A., Chamberlain, R.M., Meza, J., Remmenga, S., Seifeldin, I.A. and Soliman, A.S. (2019). Changing incidence of uterine cancer in rural Egypt: Possible impact of nutritional and epidemiologic transitions. Journal of Global Oncology, 5(n/a), 1–7. DOI: 10.1200/JGO.18.00255
Amin, M.B., Greene, F.L., Edge, S.B., Compton, C.C., Gershenwald, J.E., Brookland, R.K. and Winchester, D.P. (2017). The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging. CA: A Cancer Journal for Clinicians, 67(2), 93–9. DOI: 10.3322/caac.21388
Berek, J.S., Matias‐Guiu, X., Creutzberg, C., Fotopoulou, C., Gaffney, D., Kehoe, S. and Mutch, D. (2023). FIGO staging of endometrial cancer: 2023. International Journal of Gynecology and Obstetrics, 162(2), 383–94. DOI: 10.1002/ijgo.14923
Bokhman, J.V. (1983). Two pathogenetic types of endometrial carcinoma. Gynecologic Oncology, 15(1), 10–7. DOI: 10.1016/0090-8258(83)90111-7
Chen, B.L., Wang, H.M., Lin, X.S. and Zeng, Y.M. (2021). UPF1: A potential biomarker in human cancers. Frontiers in Bioscience-Landmark, 26(5), 76–84. DOI: 10.52586/4925
Concin, N., Matias-Guiu, X., Vergote, I., Cibula, D., Mirza, M.R., Marnitz, S. and Creutzberg, C.L. (2021). ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. International Journal of Gynecological Cancer, 31(1), 12–39. DOI: 10.1136/ijgc-2020-002230
Hüser, L., Novak, D., Umansky, V., Altevogt, P. and Utikal, J. (2018). Targeting SOX2 in anticancer therapy. Expert Opinion on Therapeutic Targets, 22(12), 983–91. DOI: 10.1080/14728222.2018.1538359
Ibrahim, A.S., Khaled, H.M., Mikhail, N.N., Baraka, H. and Kamel, H. (2014). Cancer incidence in Egypt: results of the national population‐based cancer registry program. Journal of Cancer Epidemiology, 2014(1), 437971. DOI: 10.1155/2014/437971
Kommoss, S., McConechy, M.K., Kommoss, F., Leung, S., Bunz, A., Magrill, J. and Talhouk, A. (2018). Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals of Oncology, 29(5), 1180–8. DOI: 10.1093/annonc/mdy058
Koskas, M., Amant, F., Mirza, M.R. and Creutzberg, C.L. (2021). Cancer of the corpus uteri: 2021 update. International Journal of Gynecology and Obstetrics, 155(n/a), 45–60. DOI: 10.1002/ijgo.13866
Lee, M., Choi, K.H., Oh, J.N., Kim, S.H., Lee, D.K., Choe, G.C. and Lee, C.K. (2021). SOX2 plays a crucial role in cell proliferation and lineage segregation during porcine pre‐implantation embryo development. Cell Proliferation, 54(8), e13097. DOI: 10.1111/cpr.13097
Levine, D.A. (2013). Integrated genomic characterization of endometrial carcinoma. Nature, 497(7447), 67–73. DOI: 10.1038/nature12113
Makker, V., MacKay, H., Ray-Coquard, I., Levine, D.A., Westin, S.N., Aoki, D. and Oaknin, A. (2021). Endometrial cancer. Nature Reviews Disease Primers, 7(1), 88. DOI: 10.1038/s41572-021-00324-8 
Mamun, M.A., Mannoor, K., Cao, J., Qadri, F. and Song, X. (2020). SOX2 in cancer stemness: tumor malignancy and therapeutic potentials. Journal of Molecular Cell Biology, 12(2), 85–98. DOI: 10.1093/jmcb/mjy080 
Masood, M. and Singh, N. (2021). Endometrial carcinoma: changes to classification (WHO 2020). Diagnostic Histopathology, 27(12), 493–9. DOI: 10.1016/j.mpdhp.2021.09.003
Pityński, K., Banas, T., Pietrus, M., Milian-Ciesielska, K., Ludwin, A. and Okon, K. (2015). SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading. International Journal of Clinical and Experimental Pathology, 8(7), 8189–98. DOI: PMC4555715
Rodríguez-Palacios, D.Á., Colorado-Yohar, S.M., Velten, M., Vaamonde-Martín, R.J., Ballesta, M. and Chirlaque, M.D. (2022). Incidence and trend of type I and II endometrial cancer in women from two population-based European cancer registries (1998–2012). International Journal of Environmental Research and Public Health, 19(7), 3789. DOI: 10.3390/ijerph19073789 
Salem, A.M. and Mahdy, E.R. (2018). Sex-determining region y (SRY)-Box2 (SOX2) and L1-cell adhesion molecule (L1CAM) expressions in endometrioid carcinoma of the uterus; An Immunohistochemical Study. Ann Cytol Pathol, 2(1), 1–8. DOI: 10.17352/acp.000010
Siegel, R.L., Miller, K.D., Wagle, N.S. and Jemal, A. (2023). Cancer statistics, 2023. CA: A Cancer Journal for Clinicians, 73(1), n/a DOI: 10.3322/caac.21763
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–49. DOI: 10.3322/caac.21660 
Wong, O.G.W., Huo, Z., Siu, M.K.Y., Zhang, H., Jiang, L., Wong, E.S.Y. and Cheung, A.N.Y. (2010). Hypermethylation of SOX2 promoter in endometrial carcinogenesis. Obstetrics and Gynecology International, 2010(1), 682504. DOI: 10.1155/2010/682504
Yamawaki, K., Ishiguro, T., Mori, Y., Yoshihara, K., Suda, K., Tamura, R. and Enomoto, T. (2017). Sox2‐dependent inhibition of p21 is associated with poor prognosis of endometrial cancer. Cancer Science, 108(4), 632–40. DOI: 10.1111/cas.13196
Zhang, S., Xiong, X. and Sun, Y. (2020). Functional characterization of SOX2 as an anticancer target. Signal Transduction and Targeted Therapy, 5(1), 135. DOI: 10.1038/s41392-020-00242-3 
Zhu, Y., Huang, S., Chen, S., Chen, J., Wang, Z., Wang, Y. and Zheng, H. (2021). SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial–mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer. Cell Death and Disease, 12(5), 449. DOI: 10.1038/s41419-021-03733-5