TY - JOUR
T1 - Poor outcome in hypoxic endometrial carcinoma is related to vascular density
AU - ENITEC-consortium
AU - Reijnen, Casper
AU - van Weelden, Willem Jan
AU - Arts, Martijn S. J. P.
AU - Peters, Johan P.
AU - Rijken, Paul F.
AU - van de Vijver, Koen
AU - Santacana, Maria
AU - Bronsert, Peter
AU - Bulten, Johan
AU - Hirschfeld, Marc
AU - Colas, Eva
AU - Gil-Moreno, Antonio
AU - Reques, Armando
AU - Mancebo, Gemma
AU - Krakstad, Camilla
AU - Trovik, Jone
AU - Haldorsen, Ingfrid S.
AU - Huvila, Jutta
AU - Koskas, Martin
AU - Weinberger, Vit
AU - Minar, Lubos
AU - Jandakova, Eva
AU - Snijders, Marc P. L. M.
AU - van den Berg-van Erp, Saskia
AU - Küsters-Vandevelde, Heidi V. N.
AU - Matias-Guiu, Xavier
AU - Amant, Frederic
AU - Massuger, Leon F. A. G.
AU - Bussink, Johan
AU - Pijnenborg, Johanna M. A.
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064761908&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31011231
U2 - https://doi.org/10.1038/s41416-019-0461-2
DO - https://doi.org/10.1038/s41416-019-0461-2
M3 - Article
C2 - 31011231
SN - 0007-0920
VL - 120
SP - 1037
EP - 1044
JO - British journal of cancer
JF - British journal of cancer
IS - 11
ER -