Automated subcellular localization and quantification of protein expression in tissue microarrays

Nat Med. 2002 Nov;8(11):1323-7. doi: 10.1038/nm791. Epub 2002 Oct 21.


The recent development of tissue microarrays-composed of hundreds of tissue sections from different tumors arrayed on a single glass slide-facilitates rapid evaluation of large-scale outcome studies. Realization of this potential depends on the ability to rapidly and precisely quantify the protein expression within each tissue spot. We have developed a set of algorithms that allow the rapid, automated, continuous and quantitative analysis of tissue microarrays, including the separation of tumor from stromal elements and the sub-cellular localization of signals. Validation studies using estrogen receptor in breast carcinoma show that automated analysis matches or exceeds the results of conventional pathologist-based scoring. Automated analysis and sub-cellular localization of beta-catenin in colon cancer identifies two novel, prognostically significant tumor subsets, not detected by traditional pathologist-based scoring. Development of automated analysis technology empowers tissue microarrays for use in discovery-type experiments (more typical of cDNA microarrays), with the added advantage of inclusion of long-term demographic and patient outcome information.

Publication types

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

MeSH terms

  • Algorithms
  • Cell Compartmentation
  • Cytoskeletal Proteins / metabolism
  • Neoplasms / classification
  • Neoplasms / pathology
  • Proteins / metabolism*
  • Subcellular Fractions / metabolism*
  • Trans-Activators / metabolism
  • beta Catenin


  • Cytoskeletal Proteins
  • Proteins
  • Trans-Activators
  • beta Catenin