Virchows Archiv

, Volume 469, Issue 4, pp 371–384 | Cite as

Tumour heterogeneity: principles and practical consequences

  • Giorgio StantaEmail author
  • Stephan Wenzel Jahn
  • Serena Bonin
  • Gerald Hoefler
Review and Perspectives


Two major reasons compel us to study tumour heterogeneity: firstly, it represents the basis of acquired therapy resistance, and secondly, it may be one of the major sources of the low level of reproducibility in clinical cancer research. The present review focuses on the heterogeneity of neoplastic disease, both within the primary tumour and between primary tumour and metastases. We discuss different levels of heterogeneity and the current understanding of the phenomenon, as well as imminent developments relevant for clinical research and diagnostic pathology. It is necessary to develop new tools to study heterogeneity and new biomarkers for heterogeneity. Established and new in situ methods will be very useful. In future studies, not only clonal heterogeneity needs to be addressed but also non-clonal phenotypic heterogeneity which might be important for therapy resistance. We also review heterogeneity established in major tumour types, in order to explore potential similarities that might help to define new strategies for targeted therapy.


Tumour heterogeneity Phenotypic Clonal Epigenetic Molecular Functional plasticity Intratumour Intertumour Spatial Temporal 


Compliance with ethical standards

This review was complied without the direct involvement of human participants and/or animals, but only by the analysis of published studies. Therefore, for this type of study, formal consent was not required.

Conflict of interest

The authors do not have any competing interests.


No specific funding supported the compilation of this review.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Giorgio Stanta
    • 1
    Email author
  • Stephan Wenzel Jahn
    • 2
  • Serena Bonin
    • 1
  • Gerald Hoefler
    • 2
  1. 1.Department of Medical SciencesUniversity of TriesteTriesteItaly
  2. 2.Institute of PathologyMedical University of GrazGrazAustria

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