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


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.


CONCLUSIONS
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.
Department of Oncology and Radiotherapy, University of Turku, Turku University Hospital, Finland. stavor@utu.fi
S Tuulia
ST
Avoranta
Eija A
EA
Korkeila
Heikki R I
HR
Minn
Kari J
KJ
Syrjänen
Seppo O
SO
Pyrhönen
Jari T T
JT
Sundström
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001706:Biopsy; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D064249:Securin; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil