Distinct Expression Patterns of VEGFR 1-3 in Gastroenteropancreatic Neuroendocrine Neoplasms: Supporting Clinical Relevance, but not a Prognostic Factor

胃肠胰神经内分泌肿瘤中 VEGFR 1-3 的不同表达模式:支持临床相关性,但不是预后因素

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作者:Florian Bösch, Annelore Altendorf-Hofmann, Sven Jacob, Christoph J Auernhammer, Christine Spitzweg, Stefan Boeck, Gabriele Schubert-Fritschle, Jens Werner, Thomas Kirchner, Martin K Angele, Thomas Knösel

Discussion

VEGFR 1-3 show a distinct expression pattern in different subgroups of neuroendocrine neoplasias indicating a conceivable target. Moreover, there was a substantial association between VEGFRs and immune checkpoint markers. Taken together, anti-VEGFR therapy represents a promising therapeutic approach in GEP-NEN patients and should be addressed in future studies.

Material and methods

The expression levels of VEGFR 1-3 were analyzed by immunohistochemistry and correlated with the expression of the checkpoint markers PD-1 and PD-L1. Furthermore, the tumor samples of 249 GEP-NEN patients were studied and correlated with overall survival rates and clinicopathological features. Kaplan-Meier analyses and the log rank test were used for survival analyses. Categorical variables were compared by the χ2 test.

Methods

The expression levels of VEGFR 1-3 were analyzed by immunohistochemistry and correlated with the expression of the checkpoint markers PD-1 and PD-L1. Furthermore, the tumor samples of 249 GEP-NEN patients were studied and correlated with overall survival rates and clinicopathological features. Kaplan-Meier analyses and the log rank test were used for survival analyses. Categorical variables were compared by the χ2 test.

Results

The most common primary tumor site was the small intestine (50.6%), followed by the pancreas (25.7%). VEGFR 1 was highly expressed in 59%, VEGFR 2 in 6.4%, and VEGFR 3 in 61.8% of the analyzed samples. The expression of VEGFR 1-3 was not significantly associated with survival rates. Pancreatic NENs had the highest expression of VEGFR 1 and 3 in 80% of the cases. VEGFR 1-3 positivity correlated with the expression levels of immune checkpoint markers.

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