title: High survivin expression is associated with reduced apoptosis in rectal cancer and may predict disease-free survival after preoperative radiochemotherapy and surgical resection.
abstract: BACKGROUND
  Spontaneous apoptosis has been shown to predict tumor response to preoperative radiochemotherapy in rectal cancer. It remains to be elucidated, however, which genetic profile determines whether a tumor is more or less prone to apoptosis. Recently, a novel member of the inhibitor of apoptosis family, designated survivin, was identified. In the present study, we investigated the impact of survivin on tumor cell apoptosis and the risk to develop distant metastases or local failure after preoperative radiochemotherapy and surgical resection.
  
  
  METHODS
  The expression of survivin, p53, bcl-2 and the apoptotic index was evaluated by immunohistochemistry on pretreatment biopsies of 54 patients with locally advanced adenocarcinoma of the rectum. Survivin expression was correlated to clinical and histopathological markers, the levels of spontaneous apoptosis, p53 and bcl-2, as well as to disease-free survival, 5-year rates of local failure and distant disease after preoperative radiochemotherapy and surgical resection.
  
  
  RESULTS
  Survivin expression inversely correlated with the apoptotic index: High survivin expression was found in 56% of rectal carcinoma biopsies with a median apoptotic index of 1.22%. Conversely, low survivin expression in tumor cells was associated with a high median apoptotic index (2.29%, p = 0.0001). High survivin expression also segregated with bcl-2 overexpression (65% bcl-2+ in tumors with high survivin expression as compared to 35% bcl-2+ in tumors with low survivin expression), but the difference was not statistically significant (p = 0.1). Low survivin expression was significantly related to an increased disease-free survival rate (77% vs 18% at 5 years in tumors with high survivin expression, p = 0.02) and to a reduced risk for distant metastases (18% vs 78% at 5 years in tumors with high survivin expression, p = 0.05) and local failure (6% vs 37% at 5 years in tumors with high survivin expression, p = 0.07).
  
  
  CONCLUSIONS
  An inverse correlation between survivin expression and the level of spontaneous apoptosis in pretreatment biopsies suggests that survivin strongly inhibits tumor cell apoptosis in rectal cancer. Survivin expression may provide a novel predictive indicator for disease-free survival after preoperative radiochemotherapy and surgical resection in rectal cancer.
authors.affiliation: Department of Radiation Oncology, University of Erlangen, Germany. franz.roedel@strahlen.med.uni-erlangen.de
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.forename: Jörg
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Grabenbauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Papadopoulos
authors.forename: Christian
authors.initials: C
authors.lastname: Weiss
authors.forename: Klaus
authors.initials: K
authors.lastname: Günther
authors.forename: Christoph
authors.initials: C
authors.lastname: Schick
authors.forename: Rolf
authors.initials: R
authors.lastname: Sauer
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D017024:Chemotherapy, Adjuvant; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics; D003131:Combined Modality Therapy; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis / Q000235:genetics; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins; D009364:Neoplasm Recurrence, Local; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012007:Rectum / Q000473:pathology; D000077022:Survivin; D013997:Time Factors
chemical_list: C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin