The Role of PTEN Tumor Suppressor Genes in Endometrial Cancer
A Literature Review
DOI:
https://doi.org/10.56226/114Keywords:
PTEN, Tumor suppressor, endometrial cancer, genetic mutation, P13K/AKT pathway, OncologyAbstract
Introduction: The PTEN gene is one of the main tumour suppressors, which is essential in regulating cell growth and preventing carcinogenesis. In endometrial cancer, mutations or loss of function of PTEN are frequently associated with disease progression, making this gene a relevant target for studies on molecular mechanisms and potential therapeutic approaches. Uncontrolled activation of the PI3K/AKT pathway, resulting from PTEN inactivation, favours cell proliferation and resistance to apoptosis, contributing to tumour aggressiveness. Methology: This study is based on a systematic review of the scientific literature, analysing articles published between 2010 and 2025 in databases such as PubMed, Scopus and Web of Science. Studies that investigate the relationship between PTEN mutations and the development of endometrial cancer, considering molecular, clinical and therapeutic aspects, were included. The selection of articles followed strict inclusion and exclusion criteria, prioritising research with significant samples and well-established methodologies. Results: The data analysed indicate that PTEN mutations are present in approximately 50% of endometrial cancer cases, being more frequent in high-grade tumours. These mutations compromise the function of the PTEN protein, allowing cells with DNA damage to avoid apoptosis and continue to proliferate. In addition, tumours with PTEN mutations are more resistant to conventional treatments, such as chemotherapy and radiotherapy. Recent studies suggest that inhibition of the PI3K/AKT pathway may be a promising strategy to contain tumour progression in patients with PTEN mutations. Discussion: The presence of PTEN mutations in endometrial cancer reinforces its importance as a prognostic and therapeutic biomarker. Uncontrolled activation of the PI3K/AKT pathway contributes to exacerbated cell proliferation, resistance to apoptosis, and tumour angiogenesis, favouring cancer dissemination. Therapeutic strategies aimed at modulating this pathway are being investigated, including specific PI3K inhibitors and targeted therapies. However, challenges such as heterogeneity of mutations and the interaction of PTEN with other molecular pathways require more personalised approaches for the treatment of the disease. Conclusion: The PTEN gene plays an essential role in regulating cell growth and preventing endometrial cancer. Its mutation or loss of function is directly related to tumour progression, therapeutic resistance, and poor prognosis of the disease. Understanding these mechanisms paves the way for the development of new therapeutic strategies, including targeted therapies and PI3K/AKT pathway inhibitors, which may improve clinical outcomes for patients. Future studies should focus on identifying biomarkers associated with PTEN and improving targeted therapies to optimise the management of endometrial cancer
References
Baak JP, Mutter GL (2005) EIN and WHO94. J Clin Pathol. 58(1):1–6. DOI: https://doi.org/10.1136/jcp.2004.021071
Baak, J. P., Mutter, G. L., Robboy, S., van Diest, P. J., Uyterlinde, A. M., Orbo, A., Palazzo, J., Fiane, B., Løvslett, K., Burger, C., Voorhorst, F., & Verheijen, R. H. (2005). The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer, 103(11), 2304–2312. https://doi.org/10.1002/cncr.21058 . DOI: https://doi.org/10.1002/cncr.21058
Déléris, P., Gayral, S., & Breton-Douillon, M. (2006). Nuclear Ptdlns(3,4,5)P3 signaling: an ongoing story. Journal of cellular biochemistry, 98(3), 469–485. https://doi.org/10.1002/jcb.20695 . DOI: https://doi.org/10.1002/jcb.20695
Ho, J., Cruise, E. S., Dowling, R. J. O., & Stambolic, V. (2020). PTEN Nuclear Functions. Cold Spring Harbor perspectives in medicine, 10(5), a036079. https://doi.org/10.1101/cshperspect.a036079 . DOI: https://doi.org/10.1101/cshperspect.a036079
JOSÉ ALENCAR GOMES DA SILVA NATIONAL CANCER INSTITUTE. Estimate 2023: Incidence of cancer in Brazil [Internet]. Rio de Janeiro: José Alencar Gomes da Silva National Cancer Institute; 2022 [accessed 2025 May 3]. Available at: https://www.inca.gov.br/publicacoes/livros/estimativa-2023-incidencia-de-cancer-no-brasil
Juric, D., Castel, P., Griffith, M., Griffith, O. L., Won, H. H., Ellis, H., Ebbesen, S. H., Ainscough, B. J., Ramu, A., Iyer, G., Shah, R. H., Huynh, T., Mino-Kenudson, M., Sgroi, D., Isakoff, S., Thabet, A., Elamine, L., Solit, D. B., Lowe, S. W., Quadt, C., … Scaltriti, M. (2015). Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature, 518(7538), 240–244. https://doi.org/10.1038/nature13948 . DOI: https://doi.org/10.1038/nature13948
Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia A long-term study of "untreated" hyperplasia in 170 patients. Cancer 56(2):403–412 . DOI: https://doi.org/10.1002/1097-0142(19850715)56:2<403::AID-CNCR2820560233>3.0.CO;2-X
Lacey, J. V., Jr, Mutter, G. L., Ronnett, B. M., Ioffe, O. B., Duggan, M. A., Rush, B. B., Glass, A. G., Richesson, D. A., Chatterjee, N., Langholz, B., & Sherman, M. E. (2008). PTEN expression in endometrial biopsies as a marker of progression to endometrial carcinoma. Cancer research, 68(14), 6014–6020. https://doi.org/10.1158/0008-5472.CAN-08-1154 . DOI: https://doi.org/10.1158/0008-5472.CAN-08-1154
Lacey, J. V., Jr, Sherman, M. E., Rush, B. B., Ronnett, B. M., Ioffe, O. B., Duggan, M. A., Glass, A. G., Richesson, D. A., Chatterjee, N., & Langholz, B. (2010). Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 28(5), 788–792. https://doi.org/10.1200/JCO.2009.24.1315 . DOI: https://doi.org/10.1200/JCO.2009.24.1315
Le, Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer. Cancer discovery, 6(10), 1134–1147. https://doi.org/10.1158/2159-8290.CD-16-0305 . DOI: https://doi.org/10.1158/2159-8290.CD-16-0305
Lindsay, Y., McCoull, D., Davidson, L., Leslie, N. R., Fairservice, A., Gray, A., Lucocq, J., & Downes, C. P. (2006). Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression. Journal of cell science, 119(Pt 24), 5160–5168. https://doi.org/10.1242/jcs.000133. DOI: https://doi.org/10.1242/jcs.000133
Maehama, T., & Dixon, J. E. (1998). The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. The Journal of biological chemistry, 273(22), 13375–13378. https://doi.org/10.1074/jbc.273.22.13375 . DOI: https://doi.org/10.1074/jbc.273.22.13375
Mester, J., & Eng, C. (2015). Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. Journal of surgical oncology, 111(1), 125–130. https://doi.org/10.1002/jso.23735 . DOI: https://doi.org/10.1002/jso.23735
Murali, R., Davidson, B., Fadare, O., Carlson, J. A., Crum, C. P., Gilks, C. B., Irving, J. A., Malpica, A., Matias-Guiu, X., McCluggage, W. G., Mittal, K., Oliva, E., Parkash, V., Rutgers, J. K. L., Staats, P. N., Stewart, C. J. R., Tornos, C., & Soslow, R. A. (2019). High-grade Endometrial Carcinomas: Morphologic and Immunohistochemical Features, Diagnostic Challenges and Recommendations. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, 38 Suppl 1(Iss 1 Suppl 1), S40–S63. https://doi.org/10.1097/PGP.0000000000000491 . DOI: https://doi.org/10.1097/PGP.0000000000000491
WHO World Health Organization. World Report on Violence and Health. Geneva: WHO, 2002 .
Tan, M. H., Mester, J. L., Ngeow, J., Rybicki, L. A., Orloff, M. S., & Eng, C. (2012). Lifetime cancer risks in individuals with germline PTEN mutations. Clinical cancer research : an official journal of the American Association for Cancer Research, 18(2), 400–407. https://doi.org/10.1158/1078-0432.CCR-11-2283 . DOI: https://doi.org/10.1158/1078-0432.CCR-11-2283
Travaglino, A., Raffone, A., Saccone, G., Mollo, A., De Placido, G., Insabato, L., & Zullo, F. (2019). Endometrial hyperplasia and the risk of coexisting cancer: WHO versus EIN criteria. Histopathology, 74(5), 676–687. https://doi.org/10.1111/his.13776 . DOI: https://doi.org/10.1111/his.13776
Walsh, T., Casadei, S., Lee, M. K., Pennil, C. C., Nord, A. S., Thornton, A. M., Roeb, W., Agnew, K. J., Stray, S. M., Wickramanayake, A., Norquist, B., Pennington, K. P., Garcia, R. L., King, M. C., & Swisher, E. M. (2011). Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proceedings of the National Academy of Sciences of the United States of America, 108(44), 18032–18037. https://doi.org/10.1073/pnas.1115052108 . DOI: https://doi.org/10.1073/pnas.1115052108
Yen, T. T., Wang, T. L., Fader, A. N., Shih, I. M., & Gaillard, S. (2020). Molecular Classification and Emerging Targeted Therapy in Endometrial Cancer. International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists, 39(1), 26–35. https://doi.org/10.1097/PGP.0000000000000585 . DOI: https://doi.org/10.1097/PGP.0000000000000585
Uyeda, M. (2025). Predictive Factors and Outcomes in the Management of Stage IB Endometrial Cancer: A Retrospective Study on Recurrence and Adjuvant Treatment . International Healthcare Review (online). https://doi.org/10.56226/98 DOI: https://doi.org/10.56226/98
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 The Publisher
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution (CC-BY) 4.0 License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Start-up >