Securin identifies a subgroup of patients with poor outcome in rectal cancer treated with long-course (chemo)radiotherapy

Acta Oncol. 2011 Nov;50(8):1158-66. doi: 10.3109/0284186X.2011.584327.

Abstract

Background: Securin is an oncogene with functions in cell proliferation, tumour initiation and progression. Its prognostic value in rectal cancer is somewhat unknown. Accordingly, we studied securin expression together with Ki-67 in rectal cancer in relation to preoperative (chemo)radiotherapy (RT) and disease outcome.

Material and methods: Biopsies (n = 65 for securin; n = 57 for Ki-67) and operative specimens (n = 207) from 211 patients treated with short-course RT (n = 87), long-course RT (n = 54) or surgery only (n = 70) were studied with immunohistochemistry (IHC) for securin and Ki-67 expression. In the long-course RT group, 45 patients received chemotherapy (5-fluorouracil or capecitabine) concomitantly with RT. The results of IHC were related to clinicopathological variables, disease outcome and tumour regression grade (TRG) after long-course RT.

Results: Both markers showed significant reduction after RT (p < 0.001). No differences in expression was seen in the long-course RT group between the patients with or without concomitant chemotherapy (p = 0.23 for securin; p = 0.31 for Ki-67). Low Ki-67 expression, but not that of securin, in operative specimens was significantly related to excellent TRG (p = 0.02 for Ki-67; p = 0.21 for securin). In univariate survival analysis, excellent TRG predicted longer disease-specific survival (DSS; p = 0.03). In multivariate Cox analysis, high securin expression after long-course (chemo)RT was an independent predictor of shorter DSS (p = 0.036) together with patient age (p = 0.043) and disease recurrence (local or distant; p = 0.009), whereas no similar appearance was seen in other treatment groups.

Conclusion: Securin expression in rectal cancer is significantly reduced after RT. High securin expression and poor TRG after long-course (chemo)RT are indicators of unfavourable disease outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biopsy
  • Capecitabine
  • Chemotherapy, Adjuvant
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Disease-Free Survival
  • Female
  • Fluorouracil / analogs & derivatives*
  • Fluorouracil / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / biosynthesis
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Proteins / biosynthesis*
  • Proportional Hazards Models
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Securin
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Ki-67 Antigen
  • Neoplasm Proteins
  • Securin
  • pituitary tumor-transforming protein 1, human
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil