- Volume 13 Issue 12
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Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy
- Kara, Oguz (Department of Medical Oncology, Cukurova University Medical Faculty) ;
- Duman, Berna Bozkurt (Department of Medical Oncology, Cukurova University Medical Faculty) ;
- Kara, Banu (Department of Gastroenterology, Adana Numune Education and Research Hospital) ;
- Erdogan, Seyda (Department of Pathology, Cukurova University Medical Faculty) ;
- Parsak, Cem Kaan (Department of Surgery, Cukurova University Medical Faculty) ;
- Sakman, Gurhan (Department of Surgery, Cukurova University Medical Faculty)
- Published : 2012.12.31
Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.
- Ahwon L, Woo CP, Hyeon WY, et al (2007). Expression of c-erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast. Jpn J Clin Oncol, 37, 708-14. https://doi.org/10.1093/jjco/hym082
- Asghar U, Hawkes E, Cunningham D (2010). Predictive and prognostic biomarkers for targeted therapy in metastatic colorectal cancer. Clin Colorectal Cancer, 9, 274-81. https://doi.org/10.3816/CCC.2010.n.040
- Cacheux W, Le Tourneau C, Baranger B, Mignot L, Mariani P (2011). Targeted biotherapy in metastatic colorectal carcinoma: Current practice. J Visc Surg, 148, 12-8. https://doi.org/10.1016/j.jviscsurg.2010.12.004
- Christos NP, Christopher JL (2004). Bortezomib as a potential treatment for prostate cancer. Cancer Res, 64, 5036-43. https://doi.org/10.1158/0008-5472.CAN-03-2707
- Chua W, Moore MM, Charles KA, Clarke SJ (2009). Predictive biomarkers of clinical response to targeted antibodies in colorectal cancer. Curr Opin Mol Ther, 11, 611-22.
- Colakoglu T, Yildirim S, Kayaselcuk F, et al (2008). 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, 195, 719-25. https://doi.org/10.1016/j.amjsurg.2007.05.061
- Des GG, Uzzan B, Nicolas P, et al (2006). Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer, 94, 1823-32. https://doi.org/10.1038/sj.bjc.6603176
- Hawkes E, Cunningham D (2010). Relationship between colorectal cancer biomarkers and response to epidermal growth factor receptor monoclonal antibodies. J Clin Oncol, 28, 529-31. https://doi.org/10.1200/JCO.2010.29.5626
- Herreros-Villanueva M, Rodrigo M, Claver M, et al (2011). KRAS, BRAF, EGFR and HER2 gene status in a Spanish population of colorectal cancer. Mol Biol Rep, 38, 1315-20. https://doi.org/10.1007/s11033-010-0232-x
- Jalba CS, Jalba BA, Nicula C, et al (2011). Clinical relevance of vascular endothelial growth factor-A in colorectal cancer. Rom J Morphol Embryol, 52, 775-81.
- Jemal A, Siegel R, Ward E, et al (2008). Cancer statistics, 2008. CA Cancer J Clin, 58, 71-96. https://doi.org/10.3322/CA.2007.0010
- Klos KS, Wyszomierski SL, Sun M, et al (2006). ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/ p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res, 66, 2028-37. https://doi.org/10.1158/0008-5472.CAN-04-4559
- Li Q, Wang D, Li J, Chen P (2011). Clinicopathologic and prognostic significance of HER-2/neu and VEGF expression in colon carcinoma. BMC Cancer, 11, 277. https://doi.org/10.1186/1471-2407-11-277
- Lohrum MA, Woods DB, Ludwig RL, Balint E, Vousden KH (2001). C-terminal ubiquitination of p53 contributes to nuclear export. Mol Cell Biol, 21, 8521-32. https://doi.org/10.1128/MCB.21.24.8521-8532.2001
- Longo R, Gasparini G (2007). Challenges for patient selection with VEGF inhibitors. Cancer Chemother Pharmacol, 60, 151-70. https://doi.org/10.1007/s00280-006-0403-6
- Munro AJ, Lain S, Lane DP (2005). p53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer, 92, 434-44.
- Murad JC, Ribeiro U Jr, Safatle-Ribero AV, et al (2007). Evaluation of moleculer markers in hepatic metastasis of colorectal adenocarcinoma. Hepatogastroenterology, 54, 1029-33.
- Perrone G, Santini D, Verzì A, et al (2006). COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables. J Clin Pathol, 59, 492-6. https://doi.org/10.1136/jcp.2005.030098
- Pohl M, Werner N, Munding J, et al (2011). Biomarkers of antiangiogenic therapy in metastatic colorectal cancer (mCRC): original data and review of the literature. Z Gastroenterol, 49, 1398-406. https://doi.org/10.1055/s-0031-1281752
- Sarmadi S, Izadi-Mood N, Sotoudeh K, Tavangar SM (2009). Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium. Diagn Pathol, 4, 41. https://doi.org/10.1186/1746-1596-4-41
- Yang W, Klos K, Yang Y, et al (2002). ErbB2 overexpression correlates with increased expression of vascular endothelial growth factors A, C, and D in human breast carcinoma. Cancer, 94, 2855-61. https://doi.org/10.1002/cncr.10553
- Van CE, Kohne CH, Lang I, et al (2011). Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol, 29, 2011-9. https://doi.org/10.1200/JCO.2010.33.5091
- Wei Q, Shui Y, Zheng S, et al (2011). EGFR, HER2 and HER3 expression in primary colorectal carcinomas and corresponding metastases: Implications for targeted radionuclide therapy. Oncol Rep, 25, 3-11.
- Wong R, Cunningham D (2008). Using predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodies. J Clin Oncol, 26, 5668-70. https://doi.org/10.1200/JCO.2008.19.5024
- Yen L, Benlimame N, Nie ZR, et al (2002). Differential regulation of tumor angiogenesis by distinct ErbB homo-and heterodimers. Mol Biol Cell, 13, 4029-44. https://doi.org/10.1091/mbc.E02-02-0084
- Yen L, You XL, Al Moustafa AE, et al (2000). Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene, 19, 3460-9. https://doi.org/10.1038/sj.onc.1203685
- Zhou YJ, Xiong YX, Wu XT, et al (2004). Inactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer. World J Gastroenterol, 10, 3225-9.
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- Platelet Derived Growth Factor-B and Human Epidermal Growth Factor Receptor-2 Polymorphisms in Gall Bladder Cancer vol.16, pp.14, 2015, https://doi.org/10.7314/APJCP.2015.16.14.5647
- Biomarkers of Angiogenesis in Colorectal Cancer vol.7s1, pp.1179-299X, 2015, https://doi.org/10.4137/BIC.S25250
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