Poor outcome in hypoxic endometrial carcinoma is related to vascular density

Authors	REIJNEN Casper VAN WEELDEN Willem Jan ARTS Martijn S. J. P. PETERS Johan P. RIJKEN Paul F. VAN DE VIJVER Koen SANTACANA Maria BRONSERT Peter BULTEN Johan HIRSCHFELD Marc COLAS Eva GIL-MORENO Antonio REQUES Armando MANCEBO Gemma KRAKSTAD Camilla TROVIK Jone HALDORSEN Ingfrid S. HUVILA Jutta KOSKAS Martin WEINBERGER Vít MINÁŘ Luboš JANDÁKOVÁ Eva SNIJDERS Marc P. L. M. VAN DEN BERG-VAN ERP Saskia KUSTERS-VANDEVELDE Heidi V. N. MATIAS-GUIU Xavier AMANT Frederic MASSUGER Leon F. A. G. BUSSINK Johan PIJNENBORG Johanna M. A.
Year of publication	2019
Type	Article in Periodical
Magazine / Source	British journal of cancer
MU Faculty or unit	Faculty of Medicine
Citation
Web	http://dx.doi.org/10.1038/s41416-019-0461-2
Doi	http://dx.doi.org/10.1038/s41416-019-0461-2
Keywords	CARBONIC-ANHYDRASE-IX; LYMPH-NODE METASTASIS; PROGNOSTIC-SIGNIFICANCE; MICROVESSEL DENSITY; INDUCIBLE FACTOR-1; SPACE INVASION; BREAST-CANCER; TUMOR HYPOXIA; EXPRESSION; ANGIOGENESIS
Description	BACKGROUND: Identification of endometrial carcinoma (EC) patients at high risk of recurrence is lacking. In this study, the prognostic role of hypoxia and angiogenesis was investigated in EC patients. METHODS: Tumour slides from EC patients were stained by immunofluorescence for carbonic anhydrase IX (CAIX) as hypoxic marker and CD34 for assessment of microvessel density (MVD). CAIX expression was determined in epithelial tumour cells, with a cut-off of 1%. MVD was assessed according to the Weidner method. Correlations with disease-specific survival (DSS), disease-free survival (DFS) and distant disease-free survival (DDFS) were calculated using Kaplan-Meier curves and Cox regression analysis. RESULTS: Sixty-three (16.4%) of 385 ECs showed positive CAIX expression with high vascular density. These ECs had a reduced DSS compared to tumours with either hypoxia or high vascular density (log-rank p = 0.002). Multivariable analysis showed that hypoxic tumours with high vascular density had a reduced DSS (hazard ratio [HR] 3.71, p = 0.002), DDFS (HR 2.68, p = 0.009) and a trend for reduced DFS (HR 1.87, p = 0.054). CONCLUSIONS: This study has shown that adverse outcome in hypoxic ECs is seen in the presence of high vascular density, suggesting an important role of angiogenesis in the metastatic process of hypoxic EC. Differential adjuvant treatment might be indicated for these patients.