title: Apoptotic proteins as prognostic markers and indicators of radiochemosensitivity in stage II/III rectal cancers.
abstract: OBJECTIVE
  The expression of pro-apoptotic (Bax) and anti-apoptotic (mutated p53, Bcl-2, Bclxl) proteins was determined retrospectively using immunohistochemistry in pre-treatment biopsy samples from patients with rectal cancer treated with or without preoperative chemoradiation to investigate their role as prognostic markers and indicators of radiochemosensitivity.
  
  
  METHODS
  Biopsy samples from 67 patients operated for stage II/III rectal cancer and enrolled in an active follow-up programme were examined 8-10 years after surgery. Thirty-three had been treated with immediate surgery followed, in selected cases, by adjuvant postoperative chemoradiation. Thirty-four had preoperative chemoradiation. Immunohistochemical staining was carried out using an automated immunostainer on sections of paraffin-embedded tissue.
  
  
  RESULTS
  Independent prognostic factors for rectal cancer death were pN status (hazard ratio 3.82; 95% CI 1.67-8.73) and a high level of Bclxl positivity (hazard ratio 4.75; 95% CI 2.10-10.72) according to multivariate regression analysis by stepwise selection. Bax expression was associated with downstaging and higher survival in irradiated patients (P = 0.0004).
  
  
  CONCLUSIONS
  Pretreatment evaluation of apoptotic Bax and anti-apoptotic Bclxl factors in biopsy samples of stage II/III rectal cancers may be helpful in selecting tumours that will respond to chemoradiation or in identifying patients who will have limited benefit from chemoradiation and should therefore be selected for a more aggressive systemic regimen.
authors.affiliation: Department of Medical and Surgical Critical Care, Section of General and Oncological Surgery, University of Florence, ISPO, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Fucini
authors.forename: L
authors.initials: L
authors.lastname: Messerini
authors.forename: C
authors.initials: C
authors.lastname: Saieva
authors.forename: L
authors.initials: L
authors.lastname: Orzalesi
authors.forename: V
authors.initials: V
authors.lastname: Carroni
authors.forename: N
authors.initials: N
authors.lastname: Bartolini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011836:Radiation Tolerance; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein