Determining tissue of origin for metastatic cancers: meta-analysis and literature review of immunohistochemistry performance

Appl Immunohistochem Mol Morphol. 2010 Jan;18(1):3-8. doi: 10.1097/PAI.0b013e3181a75e6d.


Background: Pathologists use various panels of immunohistochemical (IHC) stains to identify the site of tissue of origin for metastatic tumors, particularly poorly or undifferentiated cancers of unknown or uncertain origin. Although clinicians believe that immunostains contribute greatly to determining the probable primary site among 3 or more possibilities, objective evidence has not been convincingly presented. This meta-analysis reviews the objective evidence supporting this practice and summarizes the performance reported in 5 studies published between 1993 and 2007.

Methods: A literature search was conducted to identify IHC performance studies published since 1990 that were masked, included more than 3 tissues types, and used more than 50 specimens. The 5 studies found in this search were separated into 2 subgroups for analysis: those, which included only metastatic tumors (n = 368 specimens) and the blended studies, which combined primary tumors and metastases (n = 289 specimens).

Results: The meta-analysis found that IHCs provided the correct tissue identification for 82.3% (95% confidence interval = 77.4%-86.3%) of the blended primary and metastatic samples and 65.6% (95% confidence interval = 60.1%-70.7%) of metastatic cancers. This difference is both clinically and statistically significant.

Conclusions: This literature review confirms that there is still an unmet medical need in identification of the primary site of metastatic tumors. It establishes minimum performance requirements for any new diagnostic test intended to aid the pathologist and oncologist in tissue of origin determination.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Evaluation Studies as Topic
  • Humans
  • Immunohistochemistry / standards*
  • Immunohistochemistry / statistics & numerical data
  • Neoplasm Metastasis / pathology*
  • Neoplasms / diagnosis
  • Neoplasms / pathology*