Abstract B01: Lymphangiogenic gene expression is associated with lymph node recurrence and poor survival after hepatectomy for colorectal liver metastases

Abstract

Abstract Expression of the lymphangiogenic growth factors, in particular VEGF-C, are correlated with disease-free and overall survival in primary colorectal cancer (CRC). Moreover, in patients with metastatic CRC (mCRC) lymphatic invasion and lymph node metastases are correlated with worse outcome, but the biology underlying these correlations remains unknown. To study a potential relationship between tumor biology, lymphatic spread from liver metastases and outcome, we compiled a lymph-endothelium gene set the lymphangiogenesis signature comprised of six genes specifically expressed by lymph endothelial cells, or growth factors stimulating them. In primary colorectal cancer, expression of this signature correlated with increased risk of distant metastasis. When used to cluster a cohort of 119 colorectal liver metastases (CRLM) based on gene expression profiles, the signature identified an aggressive poor prognosis subtype of CRLM with mesenchymal gene expression and a stem-like tumor phenotype. RTqPCR analysis of CRLMs with and without lymph node recurrence during follow up showed that VEGF-C and neuropilin-2 were significantly higher expressed by CRLM with onward spread to the lymph nodes. We conclude that CRLM expressing high levels of lymphangiogenic genes are more likely to develop lymph node metastases during follow up and that this correlates with a general aggressive tumor biology (i.e. the mesemcnymal/stem-like phenotype) and poor survival. Post liver resection adjuvant therapy targeting onward spread to the lymph nodes may be beneficial for patients with mesenchymal-type mCRC. Citation Format: Thomas Vellinga, Dieuwke Marvin, Inne Borel Rinkes, Jeroen Hagendoorn, Onno Kranenburg. Lymphangiogenic gene expression is associated with lymph node recurrence and poor survival after hepatectomy for colorectal liver metastases. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B01.