Document Type : Original Research
Authors
- Zohreh Mirzapour Abbas abadi 1
- Fatemeh Samiee Rad 2
- Dariush Hamedi Asl 3
- Babak Rahmani 1
- Mahmood Soleimani Dodaran 4
- Amir Peimani 5
1 Department of Molecular Medicine, Faculty of Medical Sciences, Qazvin University of Medical Sciences, Qazvin, Iran
2 Department of Pathology, Faculty of Medical School, Qazvin University of Medical Sciences, Qazvin, Iran
3 Department of Pathology and Molecular Medicine, Mehr Laboratory, Hashtgerd, Iran
4 Qazvin University of Medical Sciences
5 Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran
Abstract
Background & Objective: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located at chromosome 10. PTEN is a regulator of the PI3K/AKT signaling pathway that inhibits cell proliferation and promotes apoptosis. PTEN loss of function occurs in a spectrum of cancers, including colorectal adenocarcinoma. This study aimed to investigate the probable correlation of negative PTEN expression with clinicopathological features and colorectal adenocarcinoma (CRC) patients'''' survival.
Methods: In this cross-sectional study using Immunohistochemistry stainingPTEN expression status on 151 CRC tissues was evaluated. Then the results of IHC staining was compared to those of clinicopathological features. The relationship between PTEN and KRAS mutation status was also investigated.
Results: Of 151 CRC samples, 89 (58.9%) were negative for PTEN expression. Loss of PTEN expression was associated with KRAS mutation (P
Keywords
Main Subjects
- Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021;134(7):783-91. [DOI:10.1097/CM9.0000000000001474] [PMID] [PMCID]
- Dienstmann R, Vermeulen L, Guinney J, Kopetz S, Tejpar S, Tabernero JJNrc. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. 2017;17(2):79-92. [DOI:10.1038/nrc.2016.126] [PMID]
- Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12 (18):5268 -72. [DOI:10.1158/1078-0432.CCR-05-1554] [PMID]
- Samuels Y, Waldman T. Oncogenic mutations of PIK3CA in human cancers. Curr Top Microbiol Immunol. 2010;347:21-41. [DOI:10.1007/82_2010_68] [PMID] [PMCID]
- Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 1998;95(1):29-39. [DOI:10.1016/S0092-8674(00)81780-8]
- Shen WH, Balajee AS, Wang J, Wu H, Eng C, Pandolfi PP, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007;128(1):157-70. [DOI:10.1016/j.cell.2006.11.042] [PMID]
- Yehia L, Keel E, Eng C. The Clinical Spectrum of PTEN Mutations. Annu Rev Med. 2020;71:103-16. [DOI:10.1146/annurev-med-052218-125823] [PMID]
- Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, et al. Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence? 2008;195(6):719-25. [DOI:10.1016/j.amjsurg.2007.05.061] [PMID]
- Jang KS, Song YS, Jang SH, Min KW, Na W, Jang SM, et al. Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma. Histopathology. 2010;56 (2):229 -39. [DOI:10.1111/j.1365-2559.2009.03468.x] [PMID]
- Sawai H, Yasuda A, Ochi N, Ma J, Matsuo Y, Wakasugi T, et al. Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival. 2008;8(1):1-7. [DOI:10.1186/1471-230X-8-56] [PMID] [PMCID]
- Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res. 2008;68(6):1953-61. [DOI:10.1158/0008-5472.CAN-07-5659] [PMID] [PMCID]
- Negri FV, Bozzetti C, Lagrasta CA, Crafa P, Bonasoni MP, Camisa R, et al. PTEN status in advanced colorectal cancer treated with cetuximab. Br J Cancer. 2010;102(1):162-4. [DOI:10.1038/sj.bjc.6605471] [PMID] [PMCID]
- Fernandez-Medarde A, Santos E. Ras in cancer and developmental diseases. Genes Cancer. 2011;2(3):344-58. [DOI:10.1177/1947601911411084] [PMID] [PMCID]
- Vaughn CP, Zobell SD, Furtado LV, Baker CL, Samowitz WS. Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer. 2011;50(5):307-12. [DOI:10.1002/gcc.20854] [PMID]
- Arrington AK, Heinrich EL, Lee W, Duldulao M, Patel S, Sanchez J, et al. Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci. 2012;13(10):12153-68. [DOI:10.3390/ijms131012153] [PMID] [PMCID]
- Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, et al. NCCN Guidelines Insights: Colon Cancer, Version 2.2018. J Natl Compr Canc Netw. 2018;16(4):359-69. [DOI:10.6004/jnccn.2018.0021] [PMID]
- Lin MS, Huang JX, Chen WC, Zhang BF, Fang J, Zhou Q, et al. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology. 2011;2(6):1219-24. [DOI:10.3892/ol.2011.414] [PMID] [PMCID]
- Li XH, Zheng HC, Takahashi H, Masuda S, Yang XH, Takano Y. PTEN expression and mutation in colorectal carcinomas. Oncol Rep. 2009;22(4):757-64. [DOI:10.3892/or_00000497]
- Yazdani Y, Farazmandfar T, Azadeh H, Zekavatian Z. The prognostic effect of PTEN expression status in colorectal cancer development and evaluation of factors affecting it: miR-21 and promoter methylation. J Biomed Sci. 2016;23(1):9. [DOI:10.1186/s12929-016-0228-5] [PMID] [PMCID]
- Bazzichetto C, Conciatori F, Pallocca M, Falcone I, Fanciulli M, Cognetti F, et al. PTEN as a prognostic/predictive biomarker in cancer: an unfulfilled promise? 2019;11(4):435. [DOI:10.3390/cancers11040435] [PMID] [PMCID]
- ABADI ZA, ASL DH, RAHMANI B, PEIMANI A, DODARAN MS, RAD FS. THE CLINICOPATHOLOGIC FEATURES OF COLORECTAL ADENOCARCINOMA WITH RESPECT TO MISMATCH REPAIR GENES AND KRAS STATUS: A RETROSPECTIVE STUDY.
- Richman SD, Jasani B. Predictive biomarkers and targeted therapies in Colorectal cancer. Predictive Biomarkers in Oncology: Springer; 2019. p. 423-30. [DOI:10.1007/978-3-319-95228-4_38]
- Salmena L, Carracedo A, Pandolfi PP. Tenets of PTEN tumor suppression. Cell. 2008;133(3):403-14. [DOI:10.1016/j.cell.2008.04.013] [PMID]
- Hollander MC, Blumenthal GM, Dennis PA. PTEN loss in the continuum of common cancers, rare syndromes and mouse models. Nat Rev Cancer. 2011;11(4):289-301. [DOI:10.1038/nrc3037] [PMID] [PMCID]
- Guanti G, Resta N, Simone C, Cariola F, Demma I, Fiorente P, et al. Involvement of PTEN mutations in the genetic pathways of colorectal cancerogenesis. Hum Mol Genet. 2000;9(2):283-7. [DOI:10.1093/hmg/9.2.283] [PMID]
- Naguib A, Cooke JC, Happerfield L, Kerr L, Gay LJ, Luben RN, et al. Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors. BMC Cancer. 2011;11(1):123. [DOI:10.1186/1471-2407-11-123] [PMID] [PMCID]
- Mao C, Zhou J, Yang Z, Huang Y, Wu X, Shen H, et al. KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer. PLoS One. 2012;7(5):e36653. [DOI:10.1371/journal.pone.0036653] [PMID] [PMCID]
- Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, et al. Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 2004;64(9):3014-21. [DOI:10.1158/0008-5472.CAN-2401-2] [PMID]
- Haas-Kogan D, Shalev N, Wong M, Mills G, Yount G, Stokoe DJCB. Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. 1998;8(21):1195-S1. [DOI:10.1016/S0960-9822(07)00493-9]
- Zhang HY, Liang F, Jia ZL, Song ST, Jiang ZF. PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett. 2013;6(1):161-8. [DOI:10.3892/ol.2013.1331] [PMID] [PMCID]
)