Abstract 4879: Poor outcome in hypoxic endometrial carcinoma is related to vascular density
Authors: Reijnen Casper , Weelden Willem Jan van , Arts Martijn SJP , Peters Johan P. , Rijken Paul F. , Vijver Koen van de , Santacana Maria , Bronsert Peter , Bulten Johan , Hirschfeld Marc , Colas Eva , Gil-Moreno Antonio , Reques Amando , Mancebo Gemma , Alameda Fransesc , Krakstad Camilla , Trovik Jone , Haldorsen Ingfrid S. , Huvila Jutta , Schrouwen Stefanie , Koskas Martin , Walker Francine , Weinberger Vit , Minar Lubos , Jandakova Eva , Snijders Marc PLM , Erp Saskia van den Berg-van , Küsters-Vandevelde Heidi VN , Matias-Guiu Xavier , Amant Frederic ,   ENITEC-consortium, Massuger Leon FAG , Bussink Johan , Pijnenborg Johanna MA 
Published: August 2019

Abstract
Optimal identification of endometrial carcinoma (EC) patients at high risk of recurrence is currently lacking. Hypoxia is an important feature of aggressive EC leading to activation of hypoxic and angiogenetic target genes. The present study investigates the prognostic role of hypoxia and angiogenesis in EC. Data and tissues were used from 11 collaborating European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centers. Tumor slides were stained for CAIX as a hypoxic marker and CD-34 for assessment of microvessel density (MVD) as a marker for angiogenesis. Complete slides were digitalized and analyzed using ImageJ software after exclusion of areas without tumor. A cutoff of 1% for the fraction of CAIX positive tumor cells was used. The MVD was assessed according to the Weidner method with the median as cutoff. Correlations with disease-specific survival (DSS), disease-free survival (DFS) and distant disease-free survival (DDFS) were calculated using Cox regression analysis. Sixty-three (16.4%) of 385 ECs showed positive CAIX-expression with high vascular density. Multivariable analysis showed that ECs with combined positive CAIX-expression and high vascular density had a reduced DSS (hazard ratio [HR] 3.71, p = 0.002) and DDFS (HR 2.68, p = 0.009) and a trend for reduced DFS (HR 1.87, p = 0.054). Multivariable analyses with CAIX-expression and vascular density as separate markers, showed that both were independent prognostic markers as well. This study found an impaired DSS and DDFS in ECs with positive CAIX-expression and high vascular density. Differential adjuvant treatment might be indicated for these ECs.
Citation Format: Casper Reijnen, Willem Jan van Weelden, Martijn SJP Arts, Johan P. Peters, Paul F. Rijken, Koen van de Vijver, Maria Santacana, Peter Bronsert, Johan Bulten, Marc Hirschfeld, Eva Colas, Antonio Gil-Moreno, Amando Reques, Gemma Mancebo, Fransesc Alameda, Camilla Krakstad, Jone Trovik, Ingfrid S. Haldorsen, Jutta Huvila, Stefanie Schrouwen, Martin Koskas, Francine Walker, Vit Weinberger, Lubos Minar, Eva Jandakova, Marc PLM Snijders, Saskia van den Berg-van Erp, Heidi VN Küsters-Vandevelde, Xavier Matias-Guiu, Frederic Amant, ENITEC-consortium, Leon FAG Massuger, Johan Bussink, Johanna MA Pijnenborg. Poor outcome in hypoxic endometrial carcinoma is related to vascular density [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4879.