Lipocalin 2 expression is associated with aggressive features of endometrial cancer Full Text
BMC Cancer, 05/25/2012
Mannelqvist M et al. – Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.Methods
- 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.
- Expression of LCN2 protein, found in 49% of the cases, was associated with nonendometrioid 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 (Ecadherin, N-cadherin, P-cadherin, beta-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.