Virchows Archiv

, Volume 469, Issue 6, pp 601–609 | Cite as

Pathologists and liquid biopsies: to be or not to be?

  • Paul HofmanEmail author
  • Helmut H. Popper
Review and Perspectives


Recently, the advent of therapies targeting genomic alterations has improved the care of patients with certain types of cancer. While molecular targets were initially detected in nucleic acid samples extracted from tumor tissue, detection of nucleic acids in circulating blood has allowed the development of what has become known as liquid biopsies, which provide a complementary and alternative sample source allowing identification of genomic alterations that might be addressed by targeted therapy. Consequently, liquid biopsies might rapidly revolutionize oncology practice in allowing administration of more effective treatments. Liquid biopsies also provide an approach towards short-term monitoring of metastatic cancer patients to evaluate efficacy of treatment and/or early detection of secondary mutations responsible for resistance to treatment. In this context, pathologists, who have already been required in recent years to take interest in the domain of molecular pathology of cancer, now face new challenges. The attitude of pathologists to and level of involvement in the practice of liquid biopsies, including mastering the methods employed in molecular analysis of blood samples, need close attention. Regardless of the level of involvement of pathologists in this new field, it is mandatory that oncologists, biologists, geneticists, and pathologists work together to coordinate the pre-analytical, analytical, and post-analytical phases of molecular assessment of tissue and liquid samples of individual cancer patients. The challenges include (1) implementation of effective and efficient procedures for reception and analysis of liquid and tissue samples for histopathological and molecular evaluation and (2) assuring short turn-around times to facilitate rapid optimization of individual patient treatment. In this paper, we will review the following: (1) recent data concerning the concept of liquid biopsies in oncology and its development for patient care, (2) advantages and limitations of molecular analyses performed on blood samples compared to those performed on tissue samples, and (3) short-term challenges facing pathologists in dealing with liquid biopsies of cancer patients and new strategies to early detect metastatic tumor cell clones.


Liquid biopsy Free circulating DNA Circulating tumor cells Personalized medicine Genomic alterations Pathology 


Compliance with ethical standards

The authors declare to respect all ethical standards.



Conflict of interest

PH declares receiving honoraria from pharmaceutical (AstraZeneca, Roche, Novartis, Bristol Myers Squibb, MSD) and biotechnology (Qiagen, Janssen, Biocartis) companies for advisory board meetings. HP declares receiving honoraria from pharmaceutical companies for advisory board meeting and also unrestricted grants for research (Bristol Myers Squibb, Eli Lilly, Roche, Boehringer-Ingelheim, Astra Zeneca, Novartis).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Laboratory of Clinical and Experimental Pathology, Pasteur HospitalUniversity of Nice Sophia AntipolisNice Cedex 01France
  2. 2.Liquid Biopsy Laboratory, Pasteur HospitalUniversity of Nice Sophia AntipolisNiceFrance
  3. 3.Hospital-Related Biobank (BB-0033-00025), Pasteur HospitalUniversity of Nice Sophia AntipolisNiceFrance
  4. 4.University Hospital Federation OncoAgeUniversity of Nice Sophia AntipolisNiceFrance
  5. 5.Institute of Pathology, Res. Unit Molecular Lung & Pleura PathologyMedical University of GrazGrazAustria

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