The relationship between phosphatidylinositol 3-kinase (PI3KCA) expression and clinicopathological profiles in thyroid cancer patients
Keywords:
thyroid cancer , clinical stage, PI3KCA, histological subtype, , immunohistochemistryAbstract
Background and aim: Thyroid cancer is the most common endocrine malignancy, accounting for approximately 90% of all endocrine cancers globally. Differentiated thyroid carcinomas, including follicular, papillary, and Hürthle cell carcinomas, dominate thyroid cancer cases. The PI3K/Akt signaling pathway is a key regulator of cellular growth, survival, and mobility, and its hyperactivation is linked to thyroid tumorigenesis. This study aimed to explore the association between PI3KCA expression and clinicopathological profiles, including clinical stage, histological subtype, and tumor size, in thyroid cancer patients.
Methods: An observational analytic study with a retrospective design was conducted at Hasanuddin University Hospital from 2022 to 2024. Forty-four patients diagnosed with thyroid carcinoma were selected using convenience sampling. PI3KCA expression was evaluated through immunohistochemistry, with the percentage and intensity of stained tumor cells scored and combined.
Results: The study included 44 participants, predominantly female. Clinical stage III was most common, with significant associations between higher PI3KCA expression and advanced clinical stages (p = 0.001) as well as larger tumors >4 cm (p = 0.001). Histological subtypes were predominantly papillary carcinoma (86.1% positive cases), but no significant association was observed between PI3KCA expression and histological subtype (p = 0.236). Similarly, no significant correlations were found for age (p = 0.648) or gender (p = 0.543).
Conclusions: PI3KCA expression is significantly associated with clinical stage and tumor size in thyroid carcinoma, underscoring its potential as a prognostic marker. Further research is needed to clarify its role and potential therapeutic applications.
References
Faugeras L, Pirson AS, Donckier J, Michel L, Lemaire J, Vandervorst S, . Refractory thyroid carcinoma: which systemic treatment to use? Ther Adv Med Oncol. 2018;10:1758834017752853. doi :10.1177/1758834017752853
Pham DX, Nguyen HD, Phung AHT, Bui TD, Tran TS, Tran BNH, et al. Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study. BMC Cancer. 2021;21(1):296. doi : 10.1186/s12885-021-08023-z
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.doi : 10.3322/caac.21660
Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021. Doi :10.1002/ijc.33588
Ashorobi D, Anastasopoulou C, Lopez PP. Follicular thyroid cancer. StatPearls. Treasure Island (FL): StatPearls Publishing, PMID: 30969597
Cipriani NA, Nagar S, Kaplan SP, White MG, Antic T, Sadow PM, et al. Follicular thyroid carcinoma: how have histologic diagnoses changed in the last half-century and what are the prognostic implications? Thyroid. 2015;25(11):1209-16. PMID: 26440366
Bertucci A, Bertucci F, Gonçalves A. Phosphoinositide 3-kinase (PI3K) inhibitors and breast cancer: an overview of current achievements. Cancers (Basel). 2023;15(5). Doi : 10.3390/cancers15051416
Prete A, Borges de Souza P, Censi S, Muzza M, Nucci N, Sponziello M. Update on fundamental mechanisms of thyroid cancer. Front Endocrinol (Lausanne). 2020;11:102. Doi:10.3389/fendo.2020.00102
Wu G, Mambo E, Guo Z, Hu S, Huang X, Gollin SM, et al. Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors. J Clin Endocrinol Metab. 2005;90(8):4688-93.doi : 10.1210/jc.2004-2281
Brito C, Tomás A, Azevedo A, Esteves S, Mafra M, Roque L, Pojo M. PIK3CA mutations in diffuse gliomas: an update on molecular stratification, prognosis, recurrence, and aggressiveness. Clin Med Insights Oncol. 2022;16, doi : 10.1177/11795549211068804
Alqahtani A, Ayesh HSK, Halawani H. PIK3CA gene mutations in solid malignancies: association with clinicopathological parameters and prognosis. Cancers (Basel). 2019;12(1). PMID: 31905960
Labeda I, Syarifuddin E, Uwuratuw J, Pattelongi I, Faruk M. Analysis of PIK3CA expression to clinicopathology features of colorectal cancer in Makassar, Indonesia. Int J Surg Med. 2020;6:48-52.doi : 10.5455/ijsm.PI3K-colorectal-cancer
Cizkova M, Susini A, Vacher S, Cizeron-Clairac G, Andrieu C, Driouch K, et al. PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups. Breast Cancer Res. 2012;14(1):R28.PMID: 22330809
El Ahanidi H, El Azzouzi M, Arrouchi H, Alaoui CH, Tetou M, Bensaid M, et al. AKT1 and PIK3CA activating mutations in Moroccan bladder cancer patients biopsies and matched urine. Pan Afr Med J. 2022;41(1). doi: 10.11604/pamj.2022.41.59.31383
Lai YL, Mau BL, Cheng WH, Chen HM, Chiu HH, Tzen CY. PIK3CA exon 20 mutation is independently associated with a poor prognosis in breast cancer patients. Ann Surg Oncol. 2008;15(4):1064-9. Doi : 10.1245/s10434-007-9751-7
García-Rostán G, Costa AM, Pereira-Castro I, Salvatore G, Hernandez R, Hermsem MJ, et al. Mutation of the PIK3CA gene in anaplastic thyroid cancer. Cancer Res. 2005;65(22):10199-207. doi: 10.1158/0008-5472.can-04-4259
Wu H, Wang W, Du J, Li H, Wang H, Huang L, et al. The distinct clinicopathological and prognostic implications of PIK3CA mutations in breast cancer patients from Central China. Cancer Manag Res. 2019;11:1473-92. doi: 10.2147/cmar.s195351
Mikami M, Nosho K, Yamamoto H, Takahashi T, Maehata T, Taniguchi H, et al. Mutational analysis of beta-catenin and the RAS-RAF signalling pathway in early flat-type colorectal tumours. Eur J Cancer. 2006;42(17):3065-72, doi: 10.1016/j.ejca.2006.06.029
Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncol. 2010;6(11):1771-9. doi:10.2217/fon.10.127
Suteau V, Munier M, Briet C, Rodien P. Sex bias in differentiated thyroid cancer. Int J Mol Sci. 2021;22(23). doi:10.3390/ijms222312992
Charles RP, Silva J, Iezza G, Phillips WA, McMahon M. Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis. Mol Cancer Res. 2014;12(7):979-86. PMID: 24770869
Antico-Arciuch VG, Dima M, Liao XH, Refetoff S, Di Cristofano A. Cross-talk between PI3K and estrogen in the mouse thyroid predisposes to the development of follicular carcinomas with a higher incidence in females. Oncogene. 2010;29(42):5678-86. doi:10.1038/onc.2010.308
Jiang C, Xu F, Yi D, Jiang B, Wang R, Wu L, et al. Testosterone promotes the migration, invasion and EMT process of papillary thyroid carcinoma by up-regulating Tnnt1. J Endocrinol Invest. 2024;47(1):149-66. doi: 10.1007/s40618-023-02132-1
Benvenuti S, Frattini M, Arena S, Zanon C, Cappelletti V, Coradini D, et al. PIK3CA cancer mutations display gender and tissue specificity patterns. Hum Mutat. 2008;29(2):284-8. PMID: 18022911
Jin J, Shi Y, Zhang S, Yang S. PIK3CA mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis. Acta Oncol. 2020;59(1):66-74. doi : 10.1080/0284186x.2019.1664764
Abubaker J, Jehan Z, Bavi P, Sultana M, Al-Harbi S, Ibrahim M, et al. Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population. J Clin Endocrinol Metab. 2008;93(2):611-8. PMID: 18000091.
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