Automated quantitative analysis of tissue microarray of 443 patients with colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival

J Am Coll Surg. 2014 Nov;219(5):977-87. doi: 10.1016/j.jamcollsurg.2014.07.007. Epub 2014 Jul 16.


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.

Study design: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Survival Analysis
  • Tissue Array Analysis / methods*


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2