Cancer and Metastasis Reviews

, Volume 35, Issue 1, pp 129–140 | Cite as

Molecular pathology in real time

  • Aleš Ryška


With the development of sophisticated individualized therapeutic approaches, the role of pathology in classification of tumors is enormously increasing. The solely morphological characterization of neoplastic process is no more sufficient for qualified decision on optimal therapeutic approach. Thus, morphologic diagnosis must be supplemented by molecular analysis of the lesion with emphasis on the detection of status of certain markers used as predictive factors for targeted therapy. Both intrinsic and acquired types of intratumor heterogeneity have an impact at various moments of cancer diagnostics and therapy. The primary heterogeneity of neoplastic tissue represents a significant problem in patients, where only limited biopsy samples from the primary tumor are available for diagnosis, such as core needle biopsy specimens in breast cancer, transthoracic or endobronchial biopsies in lung cancer, or endoscopic biopsies in gastric cancer. Detection of predictive markers may be influenced by this heterogeneity, and the marker detection may be falsely negative or (less probably) falsely positive. In addition, as these markers are often detected in the tissue samples from primary tumor, the differences between molecular features of the primary lesion and its metastases may be responsible for failure of systemic therapy in patients with discordant phenotype between primary and metastatic disease. The fact of tumor heterogeneity must be taken into consideration already in establishing pathological diagnosis. One has to be aware that limited biopsy specimen must not always be fully representative of the entire tumor volume. To overcome these limitations, there does not exist one single simple solution. Examination of more tissue (preference of surgical resection specimens over biopsies, whenever possible), use of ultra-sensitive methods able to identify the minute subclones as a source of possible resistance to treatment, and detection of secondary molecular events from the circulating tumor cells or circulating cell-free DNA are potential solutions how to handle this issue.


Tumor heterogeneity Evolution Liquid biopsy Limitation Molecular pathology Targeted therapy Predictive marker Resistance 



This study was supported by the program PRVOUK P37/11, by the project LM2010004, and by grant of the Czech Ministry of Health IGA No. NT14150-3/2013.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.The Fingerland Department of PathologyCharles University Medical Faculty HospitalHradec KrálovéCzech Republic

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