Lipocalin 2 expression is associated with aggressive features of endometrial cancer

<p>Abstract</p> <p>Background</p> <p>Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithel...

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Main Authors: Mannelqvist Monica, Stefansson Ingunn M, Wik Elisabeth, Kusonmano Kanthida, Raeder Maria B, Øyan Anne M, Kalland Karl-Henning, Moses Marsha A, Salvesen Helga B, Akslen Lars A
Format: Article
Language:English
Published: BMC 2012-05-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/12/169
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author Mannelqvist Monica
Stefansson Ingunn M
Wik Elisabeth
Kusonmano Kanthida
Raeder Maria B
Øyan Anne M
Kalland Karl-Henning
Moses Marsha A
Salvesen Helga B
Akslen Lars A
author_facet Mannelqvist Monica
Stefansson Ingunn M
Wik Elisabeth
Kusonmano Kanthida
Raeder Maria B
Øyan Anne M
Kalland Karl-Henning
Moses Marsha A
Salvesen Helga B
Akslen Lars A
author_sort Mannelqvist Monica
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.</p> <p>Methods</p> <p>Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.</p> <p>Results</p> <p>Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.</p> <p>Conclusion</p> <p>Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.</p>
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spelling doaj.art-8e79e64470ba4d17b86470d54251316d2022-12-22T03:27:25ZengBMCBMC Cancer1471-24072012-05-0112116910.1186/1471-2407-12-169Lipocalin 2 expression is associated with aggressive features of endometrial cancerMannelqvist MonicaStefansson Ingunn MWik ElisabethKusonmano KanthidaRaeder Maria BØyan Anne MKalland Karl-HenningMoses Marsha ASalvesen Helga BAkslen Lars A<p>Abstract</p> <p>Background</p> <p>Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.</p> <p>Methods</p> <p>Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.</p> <p>Results</p> <p>Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.</p> <p>Conclusion</p> <p>Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.</p>http://www.biomedcentral.com/1471-2407/12/169
spellingShingle Mannelqvist Monica
Stefansson Ingunn M
Wik Elisabeth
Kusonmano Kanthida
Raeder Maria B
Øyan Anne M
Kalland Karl-Henning
Moses Marsha A
Salvesen Helga B
Akslen Lars A
Lipocalin 2 expression is associated with aggressive features of endometrial cancer
BMC Cancer
title Lipocalin 2 expression is associated with aggressive features of endometrial cancer
title_full Lipocalin 2 expression is associated with aggressive features of endometrial cancer
title_fullStr Lipocalin 2 expression is associated with aggressive features of endometrial cancer
title_full_unstemmed Lipocalin 2 expression is associated with aggressive features of endometrial cancer
title_short Lipocalin 2 expression is associated with aggressive features of endometrial cancer
title_sort lipocalin 2 expression is associated with aggressive features of endometrial cancer
url http://www.biomedcentral.com/1471-2407/12/169
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