Endometriyal karsinomlarda PTEN ekspresyonunun hormon reseptörü durumu, tümör alt tipi, histolojik derece ve klinikopatolojik parametrelerle ilişkisi

Öz

Amaç: Bu çalışma, PTEN ekspresyonunun tümör özellikleri ve hastalık progresyonu ile ilişkisini incelemektedir. Endometriyal karsinom (EK), kadın genital sisteminin en yaygın malignitesidir ve genellikle Tip I (endometrioid, hormon duyarlı, iyi prognoz) ve Tip II (seröz, agresif, kötü prognoz) olarak sınıflandırılır. PTEN, hücre büyümesini düzenleyen bir tümör supresör genidir. PTEN ekspresyon kaybı özellikle Tip I EK’de sık görülmekte ve erken tümör gelişimi ile ilişkilendirilmektedir. Gereç ve yöntem: Bu çalışmada 186 EK vakası retrospektif olarak analiz edilmiştir. PTEN ekspresyonu immünohistokimyasal olarak değerlendirilmiş ve tümör boyutu, histolojik alt tip, evre, hormon reseptör durumu ve sağkalım sonuçları ile ilişkisi araştırılmıştır. Bulgular: PTEN ekspresyon kaybı olguların %81,2’sinde tespit edilmiştir. PTEN kaybı 3 cm’den büyük tümörlerde daha sık görülmesine rağmen, evre, derecelendirme, myometrial invazyon veya metastaz ile anlamlı bir ilişki göstermemiştir. p53 mutasyonu ve yüksek dereceli tümörler daha kötü sağkalım oranları ile ilişkilendirilmiştir. Östrojen (ER) ve progesteron (PR) reseptör ekspresyonu ise ağırlıklı olarak endometrioid karsinomda gözlenmiştir. Sonuç: PTEN kaybı endometrioid EK’de sık görülmekle birlikte sağkalım üzerinde doğrudan bir etkisi bulunmamaktadır. Hormon reseptör durumu ve genetik değişiklikler EK patogenezinde önemli bir rol oynamaktadır. PTEN ve diğer moleküler belirteçler üzerine yapılacak ileri çalışmalar, kişiselleştirilmiş tedavi stratejilerinin geliştirilmesine katkı sağlayabilir. Bu bulgular, PTEN kaybının erken tümör gelişiminde rol oynadığını ancak EK için kesin bir prognostik faktör olmadığını göstermektedir.

Anahtar Kelimeler

• Endometrial kanser
• PTEN
• tümör hücreleri

Association of PTEN expression with hormone receptor status, tumor subtype, histological grade, and clinicopathological parameters in endometrial carcinomas

Abstract

Purpose: This study investigates the relationship between PTEN expression and tumor characteristics and clinical outcomes in endometrial carcinoma (EC). EC is the most common malignancy of the female genital tract, typically classified into Type I (endometrioid, hormone-sensitive, favorable prognosis) and Type II (serous, aggressive, poor prognosis). PTEN is a tumor suppressor gene that regulates cell growth. Loss of PTEN expression is frequently observed in Type I EC and is associated with early tumorigenesis. Materials and methods: A retrospective analysis was conducted on 186 EC cases. PTEN expression was evaluated immunohistochemically, and its association with tumor size, histological subtype, stage, hormone receptor status, and survival outcomes was analyzed. Results: Loss of PTEN expression was detected in 81.2% of cases. While PTEN loss was more prevalent in tumors >3 cm in size, it did not show a significant correlation with stage, grading, myometrial invasion, or metastasis. p53 mutation and high-grade tumors were associated with poorer survival rates. Estrogen receptor (ER) and progesterone receptor (PR) expression were predominantly observed in endometrioid carcinoma. Conclusions: Although PTEN loss is frequently observed in endometrioid EC, it does not directly impact survival outcomes. Hormone receptor status and genetic alterations play a crucial role in EC pathogenesis. Further studies on PTEN and other molecular markers may contribute to the development of personalized treatment strategies. These findings suggest that while PTEN loss plays a role in early tumor development, it is not a definitive prognostic factor in EC.

Keywords

• Endometrial cancer
• PTEN
• tumor cells

References

1. Ayhan A, Mao TL, Suryo Rahmanto Y, et al. Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors. J Pathol Clin Res. 2015;1(3):186-193. Published 2015 May 27. doi:10.1002/cjp2.22
2. Endometrial cancer statistics. World Cancer Research Fund International. Available at: https://www.wcrf.org/cancer-trends/endometrial-cancer-statistics. Accessed February 13, 2025
3. Lee SY. Tailored Therapy Based on Molecular Characteristics in Endometrial Cancer. Biomed Res Int. 2021;2021:2068023. Published 2021 May 5. doi:10.1155/2021/2068023
4. Li HG, Liu FF, Zhu HQ, et al. Association of PTEN gene polymorphisms with liver cancer risk. Int J Clin Exp Pathol. 2015;8(11):15198-15203. Published 2015 Nov 1.
5. Bermúdez Brito M, Goulielmaki E, Papakonstanti EA. Focus on PTEN Regulation. Front Oncol. 2015;5:166. Published 2015 Jul 27. doi:10.3389/fonc.2015.00166
6. Bazzichetto C, Conciatori F, Pallocca M, et al. PTEN as a Prognostic/Predictive Biomarker in Cancer: An Unfulfilled Promise? Cancers (Basel). 2019;11(4):435. Published 2019 Mar 28. doi:10.3390/cancers11040435
7. Sangwan K, Garg M, Pathak N, Bharti L. Expression of Cyclin D1 in Hyperplasia and Carcinoma of Endometrium and Its Correlation with Histologic Grade, Tumor Type, and Clinicopathological Features. J Lab Physicians. 2020;12(3):165-170. doi:10.1055/s-0040-1721150
8. Scully MM, Palacios-Helgeson LK, Wah LS, Jackson TA. Rapid estrogen signaling negatively regulates PTEN activity through phosphorylation in endometrial cancer cells. Horm Cancer. 2014;5(4):218-231. doi:10.1007/s12672-014-0184-z

9. Athanassiadou P, Athanassiades P, Grapsa D, et al. The prognostic value of PTEN, p53, and beta-catenin in endometrial carcinoma: a prospective immunocytochemical study. Int J Gynecol Cancer. 2007;17(3):697-704. doi:10.1111/j.1525-1438.2007.00845.x
10. Jahanbakhshi F, Maleki Dana P, Badehnoosh B, et al. Curcumin anti-tumor effects on endometrial cancer with focus on its molecular targets. Cancer Cell Int. 2021;21(1):120. Published 2021 Feb 18. doi:10.1186/s12935-021-01832-z
11. Lupini L, Scutiero G, Iannone P, et al. Molecular biomarkers predicting early development of endometrial carcinoma: A pilot study. Eur J Cancer Care (Engl). 2019;28(6):e13137. doi:10.1111/ecc.13137
12. Shah SA, Mahmood MI, Ahmad N. Low Socioeconomic Status Associated with Poor Cancer Screening Perceptions in Malaysia: Analysis of Determinant of Health among General Population. Asian Pac J Cancer Prev. 2020;21(11):3137-3144. Published 2020 Nov 1. doi:10.31557/APJCP.2020.21.11.3137
13. Wu Y, Wang J, Ge L, Hu Q. Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma. Oxid Med Cell Longev. 2022;2022:5130648. Published 2022 Feb 23. doi:10.1155/2022/5130648
14. Li Y, Bian Y, Wang K, Wan XP. POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction. BMC Med Genet. 2019;20(1):202. Published 2019 Dec 21. doi:10.1186/s12881-019-0936-2
15. Eritja N, Navaridas R, Ruiz-Mitjana A, et al. Endometrial PTEN Deficiency Leads to SMAD2/3 Nuclear Translocation. Cancers (Basel). 2021;13(19):4990. Published 2021 Oct 5. doi:10.3390/cancers13194990
16. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, et al. Integrated genomic characterization of endometrial carcinoma [published correction appears in Nature. 2013 Aug 8;500(7461):242]. Nature. 2013;497(7447):67-73. doi:10.1038/nature12113
17. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Eng C. Changes in endometrial PTEN expression throughout the human menstrual cycle. J Clin Endocrinol Metab. 2000;85(6):2334-2338. doi:10.1210/jcem.85.6.6652
18. Abd El Maqsoud NM, El Gelany S. Differential Expression Patterns of PTEN in Cyclic, Hyperplastic and Malignant Endometrium: Its Relation with ER, PR and Clinicopathological Parameters. J Egypt Natl Canc Inst. 2009;21(4):323-331.
19. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983;15(1):10-17. doi:10.1016/0090-8258(83)90111-7
20. Yamagami W, Mikami M, Nagase S, et al. Japan Society of Gynecologic Oncology 2018 guidelines for treatment of uterine body neoplasms. J Gynecol Oncol. 2020;31(1):e18. doi:10.3802/jgo.2020.31.e18
21. Slomovitz BM, Coleman RL. The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res. 2012;18(21):5856-5864. doi:10.1158/1078-0432.CCR-12-0662