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Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal Carcinomas

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Abstract

Background:This study examined the role of Survivin protein, a novel inhibitor of apoptosis, in determining prognosis after curative resection of stage II colorectal carcinomas.

Methods: Expression of Survivin, P53, and BCL-2 was evaluated immunohistochemically in stage II colorectal carcinomas from 49 patients who were followed for up to 9 years after operation. The Cox proportional hazards regression model was used to examine the predictive value of several covariates.

Results: The patients comprised 33 men and 16 women with a median age of 71 years. There were 32 colonic and 17 rectal cancers comprising 40 T3 and nine T4 primary tumors. Survivin was expressed in 30 (61.2%), P53 in 30 (61.2%), and BCL-2 in 21 (42.9%) tumors. Expression of Survivin was independent of P53 or BCL-2 expression and histopathological characteristics of the tumor. The 5-year survival rate of patients with Survivin-positive tumors was significantly lower than that of patients with Survivin-negative tumors (52.5% vs. 94.1%, respectively; P = .01). On multivariate analysis, expression of Survivin (Hazard Ratio [HR] = 9; P = .03), and rectal origin of cancer (HR = 3; P = .05) were the only factors which independently predicted an increased risk of death from recurrent cancer.

Conclusion: Survivin expression within the tumor can identify patients with stage II colorectal carcinoma who are at increased risk of death from recurrent disease and might particularly benefit from adjuvant therapy.

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References

  1. Chung DC. Molecular prognostic markers and colorectal cancer: the search goes on. Gastroenterology 1998; 114: 1330–2.

    Google Scholar 

  2. Offit K. Genetic prognostic markers for colorectal cancer. N Engl J Med 2000; 342: 124–5.

    CAS  PubMed  Google Scholar 

  3. Nauta R, Stablein DM, Holyoke ED. Survival of patients with stage B2 colon carcinoma: the Gastrointestinal Tumor Study Group experience. Arch Surg 1989; 124: 180–2.

    Google Scholar 

  4. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators: efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet 1995;345:939–44.

    Google Scholar 

  5. McLeod HL, Murray GI. Tumour markers of prognosis in colorectal cancer. Br J Cancer 1999; 79: 191–203.

    CAS  PubMed  Google Scholar 

  6. Kerr JFR, Winterford CM, Harmon BV. Apoptosis: its significance in cancer and cancer therapy. Cancer 1994; 73: 2013–26.

    Google Scholar 

  7. Meterissian SH. Apoptosis: its role in the progression of and chemotherapy for carcinoma. J Am Coll Surg 1997; 184: 658–66.

    Google Scholar 

  8. Ambrosini G, Adida C, Altieri D. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature Med 1997; 3: 917–21.

    Google Scholar 

  9. LaCasse EC, Baird S, Korneluk RG, MacKenzie AE. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1999; 17: 3247–59.

    Google Scholar 

  10. LiF, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998; 396: 580–4.

    Article  CAS  PubMed  Google Scholar 

  11. Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58: 5315–20.

    CAS  PubMed  Google Scholar 

  12. Buolamwini JK. Novel anticancer drug discovery. Curr Opin Chem Biol 1999; 3: 500–9.

    Article  Google Scholar 

  13. Altieri DC, Marchisio C. Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Lab Invest 1999; 79: 1327–1333.

    Google Scholar 

  14. Sarela AI, Macadam RCA, Farmery SM, Markham AF, Guillou PJ. Expression of the anti-apoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma. Gut 2000; 46: 645–650.

    Google Scholar 

  15. Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 1995; 55: 237–41.

    CAS  PubMed  Google Scholar 

  16. Williams NS, Jass JR, Hardcastle JD. Clinicopathological assessment and staging of colorectal cancer. Br J Surg 1988; 75: 649–52.

    Google Scholar 

  17. LuC-D, Altieri DC, Tanigawa N. Expression of a novel anti-apoptosis gene, survivin, correlated with tumour cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 1998; 58: 1808–12.

    Google Scholar 

  18. Scott N, Hale A, Deakin M, et al. A histopathological assessment of the response of rectal adenocarcinoma to combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression. Eur J Surg Oncol 1998; 24: 169–173.

    Google Scholar 

  19. Kawasaki H, Altieri DC, LuCD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998; 58: 5071–4.

    Google Scholar 

  20. Swana HS, Grossman D, Anthony JN, Weiss RM, Altieri DC. Tumor content of the anti-apoptosis molecule survivin and recurrence of bladder cancer. N Engl J Med 1999; 341: 452–3.

    Google Scholar 

  21. Grossman D, McNiff JM, LiF, Altieri DC. Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma. J Invest Dermatol 1999; 113: 1076–81.

    Google Scholar 

  22. Adida C, Berrebi D, Peuchmaur M, Reyes-Mugica M, Altieri DC. Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet 1998; 351: 882–3.

    Google Scholar 

  23. Ahnen DJ, Feigl P, Quan G, et al. Ki-ras mutation and p53 overexpression predict the clinical behaviour of colorectal cancer: a southwest oncology group study. Cancer Res 1998; 58: 1149–58.

    CAS  PubMed  Google Scholar 

  24. Ward RL, Todd AV, Santiago F, O’Connor T, Hawkins NJ. Activation of the K-ras oncogene in colorectal neoplasms is associated with decreased apoptosis. Cancer 1997; 79: 1106–13.

    Article  CAS  PubMed  Google Scholar 

  25. Guo M, Bruce AH. Cell proliferation and apoptosis. Curr Opin Cell Biol 1999; 11: 745–52.

    Google Scholar 

  26. Macadam RCA, Sarela AI, Farmery SM, Robinson PA, Markham AF, Guillou PJ. Death from early colorectal carcinomas is predicted by the presence of transcripts of the REG gene family. Br J Cancer 2000; 83: 188–95.

    Google Scholar 

  27. Jaattela M. Escaping cell death: survival proteins in cancer. Exp Cell Res 1999; 248: 30–43.

    Article  CAS  PubMed  Google Scholar 

  28. Jen J, Kim H, Piantadosi S, et al. Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 1994; 331: 213–21.

    Article  CAS  PubMed  Google Scholar 

  29. Shibata D, Reale M, Lavin P, et al. The DCC protein and prognosis in colorectal cancer. N Engl J Med 1996; 335: 1727–32.

    Google Scholar 

  30. Martinez-Lopez E, Abad A, Font A, et al. Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer. Gastroenterology 1998; 114: 1180–7.

    CAS  PubMed  Google Scholar 

  31. Carethers JM, Hawn MT, Greenson JK, Hitchcock CL, Boland CR. Prognostic significance of allelic loss at chromosome 18q21 for stage II colorectal cancer. Gastroenterology 1998; 114: 1188–95.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Professorial Surgical Unit (AIS, PJG), University of Leeds, St James’s University Hospital, Leeds, England

    Abeezar I. Sarela MD & Pierre J Guillou MD

  2. Department of Histopathology (NS, JR), University of Leeds, St James’s University Hospital, Leeds, England

    Nigel Scott MD & Jane Ramsdale

  3. Department of Molecular Medicine Unit (AFM), University of Leeds, St James’s University Hospital, Leeds, England

    Alexander F. Markham PhD

  4. F Med Sci, Clinical Sciences Building, Level 8, St James’s University Hospital, Leeds LS9 7TF, England

    Pierre J Guillou MD

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  1. Abeezar I. Sarela MD
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  2. Nigel Scott MD
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  3. Jane Ramsdale
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  4. Alexander F. Markham PhD
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  5. Pierre J Guillou MD
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Sarela, A.I., Scott, N., Ramsdale, J. et al. Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal Carcinomas. Ann Surg Oncol 8, 305–310 (2001). https://doi.org/10.1007/s10434-001-0305-0

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  • DOI: https://doi.org/10.1007/s10434-001-0305-0

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