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Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer

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Abstract

Background

Chemoradiotherapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients show poor response to adjuvant CRT. We thus investigated the usefulness of survivin expression as a predictive marker of the CRT response and its characteristics.

Methods

Forty-three patients with lower rectal cancer who underwent CRT were investigated. All patients received preoperative CRT consisting of TS-1 concurrent with 40 Gy of pelvic irradiation followed by curative resection. The relationship between clinical response, or pathological response, and the expression of survivin of pre-CRT biopsy specimens was evaluated by immunohistochemistry and compared with post-CRT expression.

Results

Positive expression of survivin was observed in 26 of 43 patients (60 %) in pre-CRT specimens. Survivin was positively expressed in 77 % of stable disease cases, and 43 % of partial response (p < 0.05). Regarding the correlation between pathological response and survivin expression, positive expression of survivin was recognized in 75 % (18 of 24) of Grade 0 + 1 cases, 50 % (7 of 14) of Grade 2 cases, and 20 % (1 of 5) of Grade 3 cases. A reverse correlation was recognized between pathological responses and survivin expression (p < 0.05). There were differences in the tumor differentiation between the survivin-positive group and the negative group (p < 0.05). The expression concordance rate was 66 % between pre- and post-CRT tissues. In post-CRT tissues, nuclear survivin expression disappeared completely and cytoplasmic expression increased, especially in responder cases.

Conclusion

Survivin expression in biopsy could be an important predictive factor of preoperative CRT response.

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Abbreviations

CRT:

Chemoradiotherapy

LLND:

Lateral lymph node dissection

CR:

Complete response

PR:

Partial response

SD:

Stable disease

NES:

Nuclear export signal

CRM1:

Chromosomal region maintenance 1

CBP:

CREB-binding protein

References

  1. Kikuchi M, Mikami T, Sato T et al (2009) High Ki67, Bax, and thymidylate synthase expression well correlates with response to chemoradiation therapy in locally advanced rectal cancers: proposal of a logistic model for prediction. Br J Cancer 101:116–123

    Article  PubMed  CAS  Google Scholar 

  2. Fujimoto Y, Oya M, Kuroyanagi H et al (2009) Laparoscopic assisted intersphincteric resection following preoperative chemoradiation therapy for locally advanced lower rectal cancer: report of a case. Hepatogastroenterology 56:378–380

    PubMed  Google Scholar 

  3. Roh MS, Colangelo LH, O’Connell MJ et al (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27:5124–5130

    Article  PubMed  Google Scholar 

  4. Spiliotis J, Datsis A (2004) The surgical approach to locally recurrent rectal cancer. Tech Coloproctol 8(Suppl 1):s33–s35

    Article  PubMed  Google Scholar 

  5. Medich D, McGinty J, Parda D et al (2001) Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications. Dis Colon Rectum 44:1123–1128

    Article  PubMed  CAS  Google Scholar 

  6. Woodfield JC, Chalmers AG, Phillips N, Sagar PM (2008) Algorithms for the surgical management of retrorectal tumours. Br J Surg 95:214–221

    Article  PubMed  CAS  Google Scholar 

  7. Sadahiro S, Suzuki T, Maeda Y et al (2007) Predictors of tumor downsizing and regression with preoperative radiotherapy alone and with concomitant tegafur/uracil (UFT) for resectable advanced rectal adenocarcinoma. Hepatogastroenterology 54:1107–1112

    PubMed  Google Scholar 

  8. Koda K, Saito N, Ochia T et al (2009) Randomized, controlled study of continuous 5-FU infusion starting immediately after curative surgery for advanced colorectal cancer. Hepatogastroenterology 56:116–119

    PubMed  CAS  Google Scholar 

  9. Raderschall E, Stout K, Freier S et al (2002) Elevated levels of Rad51 recombination protein in tumor cells. Cancer Res 62:219–225

    PubMed  CAS  Google Scholar 

  10. Meyn RE, Stephens LC, Milas L (1996) Programmed cell death and radioresistance. Cancer Metastasis Rev 15:119–131

    Article  PubMed  CAS  Google Scholar 

  11. Dewey WC, Ling CC, Meyn RE (1995) Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys 33:781–796

    Article  PubMed  CAS  Google Scholar 

  12. Gudkov AV, Komarova EA (2003) The role of p53 in determining sensitivity to radiotherapy. Nat Rev Cancer 3:117–129

    Article  PubMed  CAS  Google Scholar 

  13. Rodel C, Grabenbauer GG, Papadopoulos T et al (2002) Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer. Int J Radiat Oncol Biol Phys 52:294–303

    Article  PubMed  Google Scholar 

  14. Altieri DC (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22:8581–8589

    Article  PubMed  CAS  Google Scholar 

  15. Altieri DC (2004) Molecular circuits of apoptosis regulation and cell division control: the survivin paradigm. J Cell Biochem 92:656–663

    Article  PubMed  CAS  Google Scholar 

  16. Shin S, Sung BJ, Cho YS et al (2001) An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 40:1117–1123

    Article  PubMed  CAS  Google Scholar 

  17. Peltenburg LT (2000) Radiosensitivity of tumor cells. Oncogenes and apoptosis. Q J Nucl Med 44:355–364

    PubMed  CAS  Google Scholar 

  18. Kawasaki H, Toyoda M, Shinohara H et al (2001) Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer 91:2026–2032

    Article  PubMed  CAS  Google Scholar 

  19. Sarela AI, Scott N, Ramsdale J, Markham AF, Guillou PJ (2001) Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas. Ann Surg Oncol 8:305–310

    Article  PubMed  CAS  Google Scholar 

  20. Rodel F, Hoffmann J, Grabenbauer GG et al (2002) High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection. Strahlenther Onkol 178:426–435

    Article  PubMed  Google Scholar 

  21. Suzuki Y, Oka K, Yoshida D et al (2007) Correlation between survivin expression and locoregional control in cervical squamous cell carcinomas treated with radiation therapy. Gynecol Oncol 104:642–646

    Article  PubMed  CAS  Google Scholar 

  22. Kami K, Doi R, Koizumi M et al (2005) Downregulation of survivin by siRNA diminishes radioresistance of pancreatic cancer cells. Surgery 138:299–305

    Article  PubMed  Google Scholar 

  23. Rodel F, Hoffmann J, Distel L et al (2005) Survivin as a radioresistance factor, and prognostic and therapeutic target for radiotherapy in rectal cancer. Cancer Res 65:4881–4887

    Article  PubMed  Google Scholar 

  24. Sui L, Dong Y, Ohno M et al (2002) Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors. Int J Oncol 21:315–320

    PubMed  CAS  Google Scholar 

  25. Ikeguchi M, Kaibara N (2002) Survivin messenger RNA expression is a good prognostic biomarker for esophageal carcinoma. Br J Cancer 87:883–887

    Article  PubMed  CAS  Google Scholar 

  26. Ku JH, Kwak C, Lee HS et al (2004) Expression of survivin, a novel inhibitor of apoptosis, in superficial transitional cell carcinoma of the bladder. J Urol 171:631–635

    Article  PubMed  CAS  Google Scholar 

  27. Kennedy SM, O’Driscoll L, Purcell R et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer 88:1077–1083

    Article  PubMed  CAS  Google Scholar 

  28. Trieb K, Lehner R, Stulnig T, Sulzbacher I, Shroyer KR (2003) Survivin expression in human osteosarcoma is a marker for survival. Eur J Surg Oncol 29:379–382

    Article  PubMed  CAS  Google Scholar 

  29. Capalbo G, Dittmann K, Weiss C et al (2010) Radiation-induced survivin nuclear accumulation is linked to DNA damage repair. Int J Radiat Oncol Biol Phys 77:226–234

    Article  PubMed  CAS  Google Scholar 

  30. Shirasaka T, Shimamato Y, Ohshimo H et al (1996) Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 7:548–557

    Article  PubMed  CAS  Google Scholar 

  31. Shirasaka T, Nakano K, Takechi T et al (1996) Antitumor activity of 1 M tegafur–0.4 M 5-chloro-2,4-dihydroxypyridine–1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res 56:2602–2606

    PubMed  CAS  Google Scholar 

  32. Fukushima M, Sakamoto K, Sakata M et al (2010) Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo. Oncol Rep 24:1307–1313

    PubMed  CAS  Google Scholar 

  33. Holm T, Cedermark B, Rutqvist LE (1994) Local recurrence of rectal adenocarcinoma after ‘curative’ surgery with and without preoperative radiotherapy. Br J Surg 81:452–455

    Article  PubMed  CAS  Google Scholar 

  34. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  PubMed  CAS  Google Scholar 

  35. Han N, Galandiuk S (2006) Induction chemoradiation for rectal cancer. Arch Surg 141:1246–1252 (discussion 1253)

    Google Scholar 

  36. Kuo LJ, Liu MC, Jian JJ et al (2007) Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy? Ann Surg Oncol 14:2766–2772

    Article  PubMed  Google Scholar 

  37. Shivnani AT, Small Jr. W, Stryker SJ et al (2007) Preoperative chemoradiation for rectal cancer: results of multimodality management and analysis of prognostic factors. Am J Surg 193:389–393 (discussion 393–384)

  38. Adell GC, Zhang H, Evertsson S et al (2001) Apoptosis in rectal carcinoma: prognosis and recurrence after preoperative radiotherapy. Cancer 91:1870–1875

    Article  PubMed  CAS  Google Scholar 

  39. Scott N, Hale A, Deakin M et al (1998) 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 24:169–173

    Article  PubMed  CAS  Google Scholar 

  40. Gianani R, Jarboe E, Orlicky D et al (2001) Expression of survivin in normal, hyperplastic, and neoplastic colonic mucosa. Hum Pathol 32:119–125

    Article  PubMed  CAS  Google Scholar 

  41. Mikami T, Yoshida T, Akino F et al (2003) Apoptosis regulation differs between ulcerative colitis-associated and sporadic colonic tumors. Association with survivin and bcl-2. Am J Clin Pathol 119:723–730

    Article  PubMed  Google Scholar 

  42. Rodel F, Frey B, Leitmann W et al (2008) Survivin antisense oligonucleotides effectively radiosensitize colorectal cancer cells in both tissue culture and murine xenograft models. Int J Radiat Oncol Biol Phys 71:247–255

    Article  PubMed  Google Scholar 

  43. O’Connor DS, Grossman D, Plescia J et al (2000) Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA 97:13103–13107

    Article  PubMed  Google Scholar 

  44. Stauber RH, Mann W, Knauer SK (2007) Nuclear and cytoplasmic survivin: molecular mechanism, prognostic, and therapeutic potential. Cancer Res 67:5999–6002

    Article  PubMed  CAS  Google Scholar 

  45. Fortugno P, Wall NR, Giodini A et al (2002) Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. J Cell Sci 115:575–585

    PubMed  CAS  Google Scholar 

  46. Knauer SK, Kramer OH, Knosel T et al (2007) Nuclear export is essential for the tumor-promoting activity of survivin. FASEB J 21:207–216

    Article  PubMed  CAS  Google Scholar 

  47. Riolo MT, Cooper ZA, Holloway MP et al (2012) Histone deacetylase 6 (HDAC6) deacetylates survivin for its nuclear export in breast cancer. J Biol Chem 287:10885–10893

    Google Scholar 

  48. Pfeifer D, Wallin A, Holmlund B, Sun XF (2009) Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells. J Cancer Res Clin Oncol 135:1583–1592

    Article  PubMed  CAS  Google Scholar 

  49. Li J, Xing M, Zhu M et al (2008) Glycogen synthase kinase 3beta induces apoptosis in cancer cells through increase of survivin nuclear localization. Cancer Lett 272:91–101

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

Mitsuo Shimada received a research grant from Taiho Pharmaceutical Co. Ltd. All other authors have no conflict of interest.

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Correspondence to Chie Takasu.

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Takasu, C., Shimada, M., Kurita, N. et al. Survivin expression can predict the effect of chemoradiotherapy for advanced lower rectal cancer. Int J Clin Oncol 18, 869–876 (2013). https://doi.org/10.1007/s10147-012-0470-0

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  • DOI: https://doi.org/10.1007/s10147-012-0470-0

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