Abstrakt
With the development of individualized therapy, the role of pathology in classification of tumors is increasing. The solely morphological characterization of neoplasms is no more sufficient for qualified decision on optimal treatment.
Thus, morphology must be supplemented by molecular analysis with emphasis on the detection of status of 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 from the primary tumor is 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 markers are often detected in tissue samples from primary tumor, differences between molecular features of the primary lesion and metastases may be responsible for failure of systemic therapy in patients with discordant phenotype between primary and metastatic disease. 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.