PTEN – clinical significance in colorectal cancer Review article

Main Article Content

Angelika Copija
Dariusz Waniczek
Katarzyna Walkiewicz
Łukasz Głogowski
Henryk Augustyniak
Ewa Nowakowska-Zajdel

Abstract

Phosphatase and tensin homolog deleted on chromosome ten (PTEN ) is a human suppressor gene. Its protein product is a bispecific phosphatase playing the complex role in the cell cycle regulating processes and apoptosis by the mechanism of signal transduction into the cell via tyrosine kinase B signaling pathway (PI3K/Akt/mTOR). Reduction or loss of PTEN function is implicated in the pathogenesis of many malignancies, including colorectal cancer. A gradual decrease in the function of PTEN in the sequence of transformations: normal tissue–polyp–adenocarcinoma – disseminated cancer was indicated. The relation between the PTEN loss and the higher clinical severity of colorectal cancer was observed, i.a. higher TNM status and higher tendency to form metastases, leading in some of the studies to shortened patients survival during the observation period. The potential predictive value of the PTEN function loss for the EGFR-targeted therapy in patients with advanced colorectal cancer is the subject of controversy. The potential application of PTEN assessment in clinical practice as a prognostic and/or predictive factor requires further well-designed prospective studies on larger patient population, using the unified methodology. The aim of the study is to summarize the current knowledge on the role of PTEN gene and PTEN protein in the pathogenesis of colorectal cancer and the role of PTEN in clinical practice.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Article Details

How to Cite
1.
Copija A, Waniczek D, Walkiewicz K, Głogowski Łukasz, Augustyniak H, Nowakowska-Zajdel E. PTEN – clinical significance in colorectal cancer. OncoReview [Internet]. 2016May16 [cited 2024May4];6(2(22):86-0. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/483
Section
Articles

References

1. Didkowska J, Wojciechowska U. Nowotwory złośliwe w Polsce w 2013 roku. Centrum Onkologii, Warszawa 2015.
2. Didkowska J, Wojciechowska U, Zatoński W et al. Nowotwory złośliwe w Polsce w 2009 roku. Centrum Onkologii, Warszawa 2011.
3. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759-767.
4. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004; 22: 2954-2963.
5. Lin PC, Lin JK, Lin HH et al. A comprehensive analysis of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in colorectal cancer. World J Surg Oncol 2015; 13: 186.
6. Molinari F, Frattini M. Functions and Regulation of the PTEN Gene in Colorectal Cancer. Front Oncol 2014; 16(3): 326.
7. Chi SG, Kim HJ, Park BJ et al. Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease. Gastroenterology 1998; 115: 1084-1089.
8. Chen J, Li T, Liu Q et al. Clinical and prognostic significance of HIF-1α, PTEN, CD44v6, and survivin for gastric cancer: a meta-analysis. PLoS One 2014; 9(3): e91842.
9. Zhang Y, Zhang J, Xu K et al. PTEN/PI3K/mTOR/B7-H1 signaling pathway regulates cell progression and immuno-resistance in pancreatic cancer. Hepatogastroenterology 2013; 60(127): 1766-1772.
10. Wang L, Wang WL, Zhang Y et al. Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma. Hepatol Res 2007; 37(5): 389-396.
11. Beg S, Siraj AK, Jehan Z et al. PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma. Br J Cancer 2015; 112(12): 1938-1943.
12. Wang Y, Dai B. PTEN genomic deletion defines favorable prognostic biomarkers in localized prostate cancer: a systematic review and meta-analysis. Int J Clin Exp Med 2015; 8(4): 5430-5437.
13. Lu Y, Lin YZ, LaPushin R et al. The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells. Oncogene 1999; 18: 7034-7035.
14. Cai J, Xu L, Tang H et al. The role of the PTEN/PI3K/Akt pathway on prognosis in epithelial ovarian cancer: a meta-analysis. Oncologist 2014; 19(5): 528-535.
15. Eritja N, Santacana M, Maiques O et al. Modeling glands with PTEN deficient cells and microscopic methods for assessing PTEN loss: endometrial cancer as a model. Methods 2015; 77-78: 31-40.
16. Ji Y, Zheng M, Ye S et al. PTEN and Ki67 expression is associated with clinicopathologic features of non-small cell lung cancer. J Biomed Res 2014; 28(6): 462-467.
17. Cui M, Augert A, Rongione M et al. PTEN is a potent suppressor of small cell lung cancer. Mol Cancer Res 2014; 12(5): 654-659.
18. Hager M, Haufe H, Kemmerling R et al. PTEN expression in renal cell carcinoma and oncocytoma and prognosis. Pathology 2007; 39(5): 482-485.
19. Aguissa-Touré AH, Li G. Genetic alterations of PTEN in human melanoma. Cell Mol Life Sci 2012; 69(9): 1475-1491.
20. Camara-Quintana JQ, Nitta RT, Li G. Pathology: commonly monitored glioblastoma markers: EFGR, EGFRvIII, PTEN, and MGMT. Neurosurg Clin N Am 2012; 23(2): 237-246.
21. Chow LML, Baker SJ. PTEN function in normal and neoplastic growth. Cancer Letters 2006; 241: 184-196.
22. Lin XH, Zheng HC, Takahashi H et al. PTEN expression and mutation in colorectal carcinomas. Oncol Rep 2009; 22: 757-764.
23. Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J 2004; 382: 1-11.
24. Langlois MJ, Bergeron S, Bernatchez G et al. The PTEN Phosphatase Controls Intestinal Epithelial Cell Polarity and Barrier Function: Role in Colorectal Cancer Progression. PLoS One 2010; 5(12): e15742.
25. Bowen KA, Doan HQ, Zhou BP et al. PTEN Loss Induces Epithelial-Mesenchymal Transition in Human Colon Cancer Cells. Anticancer Res 2009; 29(11): 4439-4449.
26. Jang KS, Song YS, Jang SH et al. Clinicopathological significance of nuclear PTEN expression in colorectal carcinoma. Histopathology 2010; 56: 229-239.
27. Waniczek D, Snietura M, Pigłowski W et al. Analysis of PTEN expression in large intestine polyps and its relation to the recognized histopathological and clinical risk factors for cancer development in this location. Contemp Oncol (Pozn) 2012; 16(4): 310-315.
28. Waniczek D, Śnietura M, Młynarczyk-Liszka J et al. PTEN expression profiles in colorectal adenocarcinoma and its precancerous lesions. Pol J Pathol 2013; 64(1): 15-20.
29. Colakoglu T, Yildirim S, Kayaselcuk F 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? Am J Surg 2008; 195: 719-725.
30. Hsu CP, Kao TY, Chang WL et al. Clinical significance of tumor suppressor PTEN in colorectal carcinoma. Eur J Surg Oncol 2011; 37(2): 140-147.
31. Jiang YA, Fan LF, Jiang CQ et al. Expression and significance of PTEN, hypoxia-inducible factor-1 alpha in colorectal adenoma and adenocarcinoma. World J Gastroenterol 2003; 9(3): 491-494.
32. Frattini M, Signoroni S, Pilotti S et al. Phosphatase protein homologue to tensin expression and phosphatidylinositol-3 phosphate kinase mutations in colorectal cancer. Cancer Res 2005, 65:11227.
33. Lin MS, Huang JX, Chen WC et al. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology. Oncol Lett 2011; 2(6): 1219-1224.
34. Sawai H, Yasuda A, Ochi N et al. Loss of PTEN expression is associated with colorectal cancer liver metastasis and poor patient survival. BMC Gastroenterol 2008; 8: 56.
35. Loupakis F, Pollina L, Stasi I et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol 2009; 27(16): 2622-2629.
36. Bronte G, Silvestris N, Castiglia M et al. New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS? Oncotarget 2015; 6(28): 24780-24796.
37. Therkildsen C, Bergmann TK, Henrichsen-Schnack T et al. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis. Acta Oncol 2014; 53(7): 852-864.
38. Shen Y, Yang J, Xu Z et al. Phosphatase and tensin homolog expression related to cetuximab effects in colorectal cancer patients: a meta-analysis. World J Gastroenterol 2012; 18(21): 2712-2718.
39. Yang ZY, Wu XY, Huang YF et al. Promising biomarkers for predicting the outcomes of patients with KRAS wild-type metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a systematic review with meta-analysis. Int J Cancer 2013; 133: 1914-1925.
40. García-Alfonso P, García-Foncillas J, Salazar R et al. Updated guidelines for biomarker testing in colorectal carcinoma: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol 2015; 17(4): 264-273.