Poor outcome in hypoxic endometrial carcinoma is related to vascular density.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
05
12
2018
accepted:
04
04
2019
revised:
01
04
2019
pubmed:
24
4
2019
medline:
26
2
2020
entrez:
24
4
2019
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 31011231
doi: 10.1038/s41416-019-0461-2
pii: 10.1038/s41416-019-0461-2
pmc: PMC6738053
doi:
Substances chimiques
Carbonic Anhydrase IX
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1037-1044Références
Oncotarget. 2016 Oct 25;7(43):69844-69856
pubmed: 27634881
Semin Nucl Med. 2015 Mar;45(2):101-9
pubmed: 25704383
Head Neck. 2014 Sep;36(9):1288-95
pubmed: 24668936
Am J Pathol. 2003 Nov;163(5):1801-15
pubmed: 14578181
Korean J Intern Med. 2017 Jul;32(4):589-599
pubmed: 28704917
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12596-601
pubmed: 9770531
Neuropathology. 2018 Oct;38(5):457-462
pubmed: 29952031
Br J Cancer. 2003 Jul 21;89(2):271-6
pubmed: 12865916
Int J Gynecol Cancer. 2018 Mar;28(3):514-523
pubmed: 29324536
Microvasc Res. 1995 Sep;50(2):141-53
pubmed: 8538495
Gynecol Oncol. 2013 May;129(2):292-7
pubmed: 23480871
Cancer Res. 2004 May 1;64(9):2941-55
pubmed: 15126324
Br J Cancer. 2016 Sep 6;115(6):716-24
pubmed: 27505134
PLoS One. 2018 Jul 16;13(7):e0200855
pubmed: 30011326
Gynecol Oncol. 1983 Feb;15(1):10-7
pubmed: 6822361
Lancet. 2010 Mar 6;375(9717):816-23
pubmed: 20206777
N Engl J Med. 1991 Jan 3;324(1):1-8
pubmed: 1701519
BMC Cancer. 2010 Jun 19;10:307
pubmed: 20565904
Eur J Cancer. 2015 Sep;51(13):1742-50
pubmed: 26049688
J Clin Oncol. 2001 Aug 15;19(16):3660-8
pubmed: 11504747
Int J Gynecol Cancer. 2007 Jul-Aug;17(4):897-904
pubmed: 17359291
Cancer. 1987 Oct 15;60(8 Suppl):2035-41
pubmed: 3652025
Histol Histopathol. 2013 Feb;28(2):277-84
pubmed: 23275310
Biomark Insights. 2008 Feb 1;3:45-55
pubmed: 19578493
Eur J Cancer. 2013 Nov;49(16):3431-41
pubmed: 23932335
Am J Physiol. 1996 Oct;271(4 Pt 1):C1172-80
pubmed: 8897823
Br J Cancer. 2007 Jan 15;96(1):104-9
pubmed: 17213826
J Appl Physiol (1985). 2000 Apr;88(4):1474-80
pubmed: 10749844
Surg Pathol Clin. 2016 Jun;9(2):329-37
pubmed: 27241112
Mol Oncol. 2008 Jun;2(1):41-53
pubmed: 19383328
Oncotarget. 2015 Nov 24;6(37):39676-91
pubmed: 26485755
Biochim Biophys Acta. 2012 Dec;1826(2):272-96
pubmed: 22579961
Br J Cancer. 1999 Feb;79(5-6):991-5
pubmed: 10070902
Arch Gynecol Obstet. 2018 Mar;297(3):731-740
pubmed: 29327157
J Exp Biol. 1998 Apr;201(Pt 8):1153-62
pubmed: 9510527
Br J Cancer. 2014 Jan 7;110(1):107-14
pubmed: 24178757
World J Surg. 1997 Jan;21(1):49-56
pubmed: 8943177
J Clin Pathol. 2005 Feb;58(2):172-7
pubmed: 15677538
Adv Exp Med Biol. 2014;772:55-81
pubmed: 24272354
Oncogene. 2010 Feb 4;29(5):625-34
pubmed: 19946328
Biomed Res Int. 2014;2014:616850
pubmed: 24745019
Radiother Oncol. 2003 Apr;67(1):3-15
pubmed: 12758235
Nat Rev Cancer. 2014 Jun;14(6):430-9
pubmed: 24827502
Cancer Metastasis Rev. 1998 Jun;17(2):187-94
pubmed: 9770115
Pathobiology. 2016;83(2-3):61-9
pubmed: 27100343