Study of Survivin: A Biomarker in Carcinoma Colon – An Original Study
Keywords:
Survivin, Carcinoma colon, Antiapoptotic protein, Immunoreactivity Scoring System
Abstract
Background: Survivin, an anti-apoptotic protein has been of importance in colon carcinoma patient. Here we studied the prevalence of Survivin biomarker among cases of colon carcinoma and its relationship with other prognostic indicators. Design: Tissue samples from 102 patients with colon carcinoma were studied. H&E stain and immunohistochemistry were performed and evaluated. Immuno-histochemistry expression was sought according to IRS Scoring System (Immunoreactivity Scoring) for stain intensity and percentage positive cells. Survivin expression was also correlated with age at diagnosis, gender, grade, nodal status, lympho-vascular and perineural invasion, resection margins, Tumor stage (TNM) and Group Stage. Result and discussion: Survivin was expressed in high grade and stage tumors and showed significant association (p value= 0.002). Survivin expression was positive in lymph node positive tumors and showed significant association (p value= 0.002). Survivin was expressed in tumors with lympho-vascular and perineural invasion and showed significant association (p value= 0.02 and 0.001) respectively. Age at diagnosis showed significance of p=0.03 whereas Gender (Male/Female) and resection margins did not show any association with Survivin expression. Conclusion: Survivin expression increases as the tumor grade worsens in colon cancer and is maintained in approximately all high group staged tumors (TNM Staging) along with tumors showing lymphovascular and perineural invasion. Gender does not have any association.References
1. Ali I, Wani WA, Saleem K. Cancer Scenario in India with Future Perspectives. 2011;8:56-70.
2. Divitiis C De, Nasti G, Montano M, et al. Prognostic and predictive response factors in colorectal cancer patients : Between hope and reality. 2014;20(41):15049-15059.
3. Press D. Prognostic stratification of colorectal cancer patients : current perspectives. 2014:291-300.
4. Khan Z, Khan AA, Yadav H, Prasad GBKS, Bisen PS. Survivin , a molecular target for therapeutic interventions in squamous cell carcinoma. 2017:1-32
5. Jaiswal P, Goel A, Mittal R. Survivin: A molecular biomarker in cancer. Indian J Med Res. 2015;141(4):389-397.
6. Taubert H, Heidenreich C, Holzhausen H-J, et al. Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients. BMC Cancer. 2010;10:65.
7. Amin MB, Greene FL, Edge SB. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99.
8. Sarela GK. Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma. Gut. 2000;46(5):645-650.
9. Kawasaki, Hiroshi, et al. "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer." Cancer research 58.22 (1998): 5071-5074
10. Hamilton SR, Aaltonen LA. World Health Organization Classification of Tumours Pathology and Genetics of Edited by. 2000.
11. Lykke J, Rosenberg J, Jess P, Roikjaer O. Lymph node yield and tumour subsite are associated with survival in stage I-III colon cancer: Results from a national cohort study. World J Surg Oncol. 2019;17(1):1-8.
12. Zhou R, Zhang J, Zeng D, et al. Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I–III colon cancer. Cancer Immunol Immunother. 2019;68(3):433-442.
13. Landau MA, Zhu B, Akwuole FN, Pai RK. Histopathological Predictors of Recurrence in Stage III Colon Cancer: Reappraisal of Tumor Deposits and Tumor Budding Using AJCC8 Criteria. Int J Surg Pathol. 2019;27(2):147-158.
14. Bonetti LR, Barresi V, Maiorana A, Manfredini S, Caprera C, Bettelli S. Clinical impact and prognostic role of KRAS/BRAF/PIK3CA mutations in stage I colorectal cancer. Dis Markers. 2018;2018, 2959801.
15. Wheatley SP, Altieri DC. Survivin at a glance. J Cell Sci. 2019;132(7):223826.
16. Lazo JS, Sharlow ER. Drugging Undruggable Molecular Cancer Targets. Annu Rev Pharmacol Toxicol. 2016;56:23-40.
17. Deveraux QL, Stennicke HR, Salvesen GS, Reed JC. Endogenous inhibitors of caspases. J Clin Immunol. 1999;19(6):388-398.
18. Uren AG, Wong L, Pakusch M. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. :1319-1328.
19. Li F, Yang J, Ramnath N, Javle MM, Tan D. Nuclear or cytoplasmic expression of survivin: what is the significance? Int J cancer. 2005;114(4):509-512.
20. Dohi T, Beltrami E, Wall NR, Plescia J, Altieri DC. Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J Clin Invest. 2004;114(8):1117-1127.
21. Khan S, Bennit HF, Wall NR. The emerging role of exosomes in survivin secretion. Histol Histopathol. 2015;30(1):43-50.
22. Li F, Ackermann EJ, Bennett CF. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol. 1999;1(8):461-466.
23. Antonio CH, Tsai F, Lee JY. Survivin – biology and potential as a therapeutic target in oncology. 2013:1453-1462.
24. Fernandez JG, Rodriguez DA, Valenzuela M. Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced beta-catenin/Tcf-Lef dependent transcription. Mol Cancer. 2014;13:209.
25. Virrey JJ, Guan S, Li W, Schonthal AH, Chen TC, Hofman FM. Increased survivin expression confers chemoresistance to tumor-associated endothelial cells. Am J Pathol. 2008;173(2):575-585.
26. Hoggatt J, Singh P, Sampath J, Pelus LM. Prostaglandin E 2 enhances hematopoietic stem cell homing , survival and proliferation. 2017;113(22):5444-6.
27. Mull AN, Klar A, Navara CS. Differential localization and high expression of SURVIVIN splice variants in human embryonic stem cells but not in differentiated cells implicate a role for SURVIVIN in pluripotency. Stem Cell Res. 2014;12(2):539-549.
28. Gurbuxani S, Xu Y, Keerthivasan G, Wickrema A, Crispino JD. Differential requirements for survivin in hematopoietic cell development. Proc Natl Acad Sci U S A. 2005;102(32):11480-5.
2. Divitiis C De, Nasti G, Montano M, et al. Prognostic and predictive response factors in colorectal cancer patients : Between hope and reality. 2014;20(41):15049-15059.
3. Press D. Prognostic stratification of colorectal cancer patients : current perspectives. 2014:291-300.
4. Khan Z, Khan AA, Yadav H, Prasad GBKS, Bisen PS. Survivin , a molecular target for therapeutic interventions in squamous cell carcinoma. 2017:1-32
5. Jaiswal P, Goel A, Mittal R. Survivin: A molecular biomarker in cancer. Indian J Med Res. 2015;141(4):389-397.
6. Taubert H, Heidenreich C, Holzhausen H-J, et al. Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients. BMC Cancer. 2010;10:65.
7. Amin MB, Greene FL, Edge SB. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99.
8. Sarela GK. Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma. Gut. 2000;46(5):645-650.
9. Kawasaki, Hiroshi, et al. "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer." Cancer research 58.22 (1998): 5071-5074
10. Hamilton SR, Aaltonen LA. World Health Organization Classification of Tumours Pathology and Genetics of Edited by. 2000.
11. Lykke J, Rosenberg J, Jess P, Roikjaer O. Lymph node yield and tumour subsite are associated with survival in stage I-III colon cancer: Results from a national cohort study. World J Surg Oncol. 2019;17(1):1-8.
12. Zhou R, Zhang J, Zeng D, et al. Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I–III colon cancer. Cancer Immunol Immunother. 2019;68(3):433-442.
13. Landau MA, Zhu B, Akwuole FN, Pai RK. Histopathological Predictors of Recurrence in Stage III Colon Cancer: Reappraisal of Tumor Deposits and Tumor Budding Using AJCC8 Criteria. Int J Surg Pathol. 2019;27(2):147-158.
14. Bonetti LR, Barresi V, Maiorana A, Manfredini S, Caprera C, Bettelli S. Clinical impact and prognostic role of KRAS/BRAF/PIK3CA mutations in stage I colorectal cancer. Dis Markers. 2018;2018, 2959801.
15. Wheatley SP, Altieri DC. Survivin at a glance. J Cell Sci. 2019;132(7):223826.
16. Lazo JS, Sharlow ER. Drugging Undruggable Molecular Cancer Targets. Annu Rev Pharmacol Toxicol. 2016;56:23-40.
17. Deveraux QL, Stennicke HR, Salvesen GS, Reed JC. Endogenous inhibitors of caspases. J Clin Immunol. 1999;19(6):388-398.
18. Uren AG, Wong L, Pakusch M. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. :1319-1328.
19. Li F, Yang J, Ramnath N, Javle MM, Tan D. Nuclear or cytoplasmic expression of survivin: what is the significance? Int J cancer. 2005;114(4):509-512.
20. Dohi T, Beltrami E, Wall NR, Plescia J, Altieri DC. Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J Clin Invest. 2004;114(8):1117-1127.
21. Khan S, Bennit HF, Wall NR. The emerging role of exosomes in survivin secretion. Histol Histopathol. 2015;30(1):43-50.
22. Li F, Ackermann EJ, Bennett CF. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol. 1999;1(8):461-466.
23. Antonio CH, Tsai F, Lee JY. Survivin – biology and potential as a therapeutic target in oncology. 2013:1453-1462.
24. Fernandez JG, Rodriguez DA, Valenzuela M. Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced beta-catenin/Tcf-Lef dependent transcription. Mol Cancer. 2014;13:209.
25. Virrey JJ, Guan S, Li W, Schonthal AH, Chen TC, Hofman FM. Increased survivin expression confers chemoresistance to tumor-associated endothelial cells. Am J Pathol. 2008;173(2):575-585.
26. Hoggatt J, Singh P, Sampath J, Pelus LM. Prostaglandin E 2 enhances hematopoietic stem cell homing , survival and proliferation. 2017;113(22):5444-6.
27. Mull AN, Klar A, Navara CS. Differential localization and high expression of SURVIVIN splice variants in human embryonic stem cells but not in differentiated cells implicate a role for SURVIVIN in pluripotency. Stem Cell Res. 2014;12(2):539-549.
28. Gurbuxani S, Xu Y, Keerthivasan G, Wickrema A, Crispino JD. Differential requirements for survivin in hematopoietic cell development. Proc Natl Acad Sci U S A. 2005;102(32):11480-5.
Published
2020-11-30
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Original Article
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