title: Automated quantitative analysis of tissue microarray of 443 patients with colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival.
abstract: BACKGROUND
  Bcl-2 has been implicated in the development and progression of a number of cancers including colorectal cancer. Reports of Bcl-2 expression in colorectal cancer and patient outcomes have been inconsistent due to small cohorts and semi-quantitative grading methods.
  
  
  METHODS
  We used a high throughput tissue microarray system (automated quantitative analysis [AQUA]), analyzing colorectal adenocarcinoma samples from 443 patients resected during the period of 1967 to 1986. This system uses fully quantitative, automated fluorescent microscopy to accurately assess Bcl-2 expression in colorectal cancer samples. Clinicopathologic variables were collected prospectively and were assessed using log-rank tests and Cox proportional hazards models.
  
  
  RESULTS
  At a median follow-up of 54 months, the 5- and 10-year disease-specific survivals for all patients were 59.2% and 52.1%, respectively. Loss of Bcl-2 expression was seen in 70.4% of tumors and was associated with a decreased 5-year disease-specific survival (55.8% vs 75.6%, p = 0.001 and relative risk [RR] 1.8) and decreased 5-year overall survival (45.8% vs 56.5%, p = 0.046 and RR 1.2). On univariate analysis, T stage, N stage, and loss of Bcl-2 expression predicted poor disease-specific survival. On multivariate analysis, Bcl-2 expression was an independent prognostic factor for disease-specific survival (p = 0.034).
  
  
  CONCLUSIONS
  Our results indicate that loss of Bcl-2 expression in colorectal cancer is associated with decreased disease-specific and overall survival. This finding may help identify a subset of patients with a more aggressive phenotype and guide adjuvant chemotherapy choices.
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT.
authors.forename: Allen D
authors.initials: AD
authors.lastname: Nicholson
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT.
authors.forename: Catherine A W
authors.initials: CA
authors.lastname: Sullivan
authors.affiliation: Department of Surgery, Yale School of Medicine, New Haven, CT. Electronic address: charles.cha@yale.edu.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Cha
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2