Conclusion
There are clear molecular discrepancies at the telomeric and DDR level between primary tumors and their corresponding metastases. Our results may have important implications for the development of molecular targeted therapies aiming at DNA damage repair and telomeric components. Our findings suggest that primary tumors and their relevant metastases may respond differently to such approaches.
Material and methods
We studied a single series of 21 patients who had undergone surgery of both their primary lung tumor and its related adrenal gland metastasis in a single Institution. DDR and telomeric proteins were analysed by immunohistochemistry and telomere length was assessed by fluorescent in situ hybridization in 17 paired samples.
Methods
We studied a single series of 21 patients who had undergone surgery of both their primary lung tumor and its related adrenal gland metastasis in a single Institution. DDR and telomeric proteins were analysed by immunohistochemistry and telomere length was assessed by fluorescent in situ hybridization in 17 paired samples.
Results
DDR activation was observed in primary tumors and their corresponding metastasis. However, higher levels of p-Chk2 were observed in metastasis than in primary tumors (p=0.0113). This was not observed for p-ATM and gamma-H2AX. Telomere length was independent from primary or metastatic status (p=0.29). There was no correlation between primary and metastatic sites, although approximately 65% of metastases had shorter telomeres than their corresponding primary tumors. In the same way, telomeric protein expression was independent from primary/metastatic localization. Cluster analysis of each specimen according to its protein's expression levels and telomere length showed that matched primary tumors/adrenal metastasis were mostly separated into different clusters. Overall, our findings suggest that the levels of biomarkers analysed differ substantially between primary lung tumors and corresponding metastases.