SSAT - Evaluation of Chromosal Aberrations in the Primary Tumor, Lymph Node Metastases and Disseminated Tumor Cells of Patients With Esophageal Cancer: Implications for Anti-Tumoral Therapy?

Evaluation of Chromosal Aberrations in the Primary Tumor, Lymph Node Metastases and Disseminated Tumor Cells of Patients With Esophageal Cancer: Implications for Anti-Tumoral Therapy?
Daniel Vallbohmer^*¹, Sarah Schumacher¹, Stephan E. Baldus², Christian Vay¹, Andreas Krieg¹, Jan Schulte Am Esch¹, Wolfram T. Knoefel¹, Nikolas H. Stoecklein¹
¹Department of General, Visceral and Paediatric Surgery, University of Dusseldorf, Dusseldorf, Germany; ²Department of Pathology, University of Dusseldorf, Dusseldorf, Germany

Introduction: Recent analyses uncovered genetic variations between paired samples from primary gastrointestinal tumors, lymph node metastases and disseminated tumor cells (DTCs). These findings might help to explain individually variable responses to standard (neo-)adjuvant therapies and further suggest that multimodality treatment options in gastrointestinal cancer should be guided by these individual genetic tumor characteristics. Therefore, we assessed the genetic variations in the primary tumor, lymph node metastases and DTCs of patients with esophageal cancer.
Patients and Methods: In this translational analysis 86 patients with esophageal cancer undergoing multimodality therapy were included. Initially, we established a protocol for double immunofluorescence labeling for simultaneous visualization of epithelial cell adhesion molecule (EpCAM) expression on cytokeratin positive cells for the detection of DTCs in bone marrow and lymph nodes. After isolation of positively stained cells, their genomic DNA was globally amplified using the MSE-adapter PCR method. Finally, we applied comparative genomic hybridization (CGH) for the genome-wide screening of DNA-gains/-losses on paired samples from primary tumors, lymph node metastases and DTCs of the study patients.
Results: DTCs were detected in 25% of the bone marrow and 38% of the lymph node samples. Interestingly, CGH analysis revealed differences between the numbers of chromosal aberrations in DTCs of the bone marrow compared to the lymph node samples with a higher frequency of aberrations in DTCs in the lymph node samples. In addition, genomic analysis revealed differences in the nature of chromosomal aberrations between primary tumors and corresponding lymph node metastases. Moreover, cluster analysis demonstrated similarities of the aberration spectrum between the DTCs and lymph node metastases while primary tumors showed distinct profiles.
Conclusion: Chromosal aberration patterns in lymph node metastases and disseminated tumor cells of patients with esophageal cancer undergoing multimodality therapy are very similar while primary tumors show a different genomic aberration pattern. These individual genetic tumor characteristics might guide future multimodality treatment options in esophageal cancer.

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