Increased spontaneous apoptosis, but not survivin expression, is associated with histomorphologic response to neoadjuvant chemoradiation in rectal cancer
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Survivin has been shown to be an important mediator of cellular radioresistance in vitro. This study aims to compare survivin expression and apoptosis to histomorphologic responses to neoadjuvant radiochemotherapy (RCT) in rectal cancer.
Materials and methods
Thirty-six pre-treatment biopsies were studied. Survivin mRNA and protein expression plus TUNEL staining for apoptosis was performed. Response to treatment was assessed using a 5-point tumour regression grade.
Survivin expression was not found to be predictive of response to RCT (p = NS). In contrast, spontaneous apoptosis was significantly (p = 0.0051) associated with subsequent response to RCT. However, no association between survivin expression and levels of apoptosis could be identified.
This in vivo study failed to support in vitro studies showing an association between survivin and response to chemotherapy and radiation therapy. These results caution against the translation of the in vitro properties of survivin into a clinical setting.
KeywordsSurvivin Rectal cancer Chemoradiotherapy Tumour regression grade Apoptosis
This work was supported by a grant from the Health and Research Board, Ireland. We would like to thank Mr. Paul Quinlan, Department of Medical Illustration, Trinity College, Dublin for assistance with figures.
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.Reerink O, Karrenbeld A, Plukker JT et al (2004) Molecular prognostic factors in locally irresectable rectal cancer treated preoperatively by chemo-radiotherapy. Anticancer Res 2C:1217–221Google Scholar
- 6.Valentini V, Coco C, Picciocchi A et al (2002) Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 3:664–674Google Scholar
- 10.Van Den Brink M, Van Den Hout WB, Stiggelbout AM et al (2004) Cost-utility analysis of preoperative radiotherapy in patients with rectal cancer undergoing total mesorectal excision: a study of the Dutch Colorectal Cancer Group. J Clin Oncol 2:244–253Google Scholar
- 12.Dahlberg M, Stenborg A, Pahlman L et al (2002) Cost-effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial. Int J Radiat Oncol Biol Phys 3:654–660Google Scholar
- 13.Habr-Gama A, Perez RO, Nadalin W et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 4:711–717 discussion 717–8Google Scholar
- 16.Knutsen A, Adell GSun XF (2004) Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy. Int J Radiat Oncol Biol Phys 1:149–155Google Scholar
- 17.Adida C, Crotty PL, McGrath J et al (1998) Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1:43–49Google Scholar
- 19.Rodel C, Haas J, Groth A et al (2003) Spontaneous and radiation-induced apoptosis in colorectal carcinoma cells with different intrinsic radiosensitivities: survivin as a radioresistance factor. Int J Radiat Oncol Biol Phys 5:1341–1347Google 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 8:426–435Google Scholar
- 22.Chen WC, Liu Q, Fu JX et al (2004) Expression of survivin and its significance in colorectal cancer. World J Gastroenterol 19:2886–2889Google Scholar
- 24.Tan HY, Liu J, Wu SM et al (2005) Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma. World J Gastroenterol 30:4689–4692Google Scholar
- 25.Terzi C, Canda AE, Sagol O et al (2008) Survivin, p53, and Ki-67 as predictors of histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Int J Colorectal Dis 1:37–45Google Scholar
- 26.Sobin LH, Wittekind C (2002) TNM classification of malignant tumours, 6th edn. Wiley-Liss, New JerseyGoogle Scholar
- 31.Stipa F, Lucandri G, Ferri M et al (2004) Local excision of rectal cancer with transanal endoscopic microsurgery (TEM). Anticancer Res 2C:1167–1172Google Scholar
- 32.Ruo L, Guillem JG, Minsky BD et al (2002) Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers. Int J Colorectal Dis 1:54–58Google Scholar
- 33.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 2:294–303Google Scholar
- 35.Lin LJ, Zheng CQ, Jin Y et al (2003) Expression of survivin protein in human colorectal carcinogenesis. World J Gastroenterol 5:974–977Google Scholar
- 38.Agui T, McConkey DJ, Tanigawa N (2002) Comparative study of various biological parameters, including expression of survivin, between primary and metastatic human colonic adenocarcinomas. Anticancer Res 3:1769–776Google Scholar