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. 2010 Jun 19:10:307.
doi: 10.1186/1471-2407-10-307.

Necrosis related HIF-1alpha expression predicts prognosis in patients with endometrioid endometrial carcinoma

Laura M S Seeber  1 , Nicole Horrée, Petra van der Groep, Elsken van der Wall, René H M Verheijen, Paul J van Diest
Affiliations

Necrosis related HIF-1alpha expression predicts prognosis in patients with endometrioid endometrial carcinoma

Laura M S Seeber et al. BMC Cancer. .

Abstract

Background: Hypoxia inducible factor 1alpha (HIF-1alpha) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27kip1, which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1alpha and p27kip expression in patients with endometrioid endometrial cancer.

Methods: Expression levels of HIF-1alpha, CAIX, Glut-1, and p27kip1 were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted.

Results: Necrosis was correlated with shortened disease free survival (DFS) (p = 0.008) and overall survival (OS) (p = 0.045). For DFS, perinecrotic HIF-1alpha expression was also prognostic (p = 0.044). Moreover, high p27kip1 expression was an additional prognostic factor for these patients with perinecrotic HIF-1alpha expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1alpha expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1.

Conclusions: In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1alpha are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of HIF-1α, CAIX, Glut-1 and p27kip1 in endometrioid endometrial carcinoma. Typical patterns are shown: A) perinecrotic HIF-1α expression (10× magnification). B) Diffuse HIF-1α expression (10× magnification). C) Diffuse p27kip1 expression (10× magnification). D) Perinecrotic Glut-1 expression (10× magnification) E) Membrane CAIX expression (20× magnification). Asterisk indicates necrosis.
Figure 2
Figure 2
Kaplan-Meier survival curves illustrating disease-free survival and overall survival for endometrioid endometrial carcinoma patients (n = 93) with tumour necrosis (A, B) and patients with perinecrotic type HIF-1α expression (C, D). E and F show the survival for the patients with perinecrotic HIF-1α expression (n = 51) and high p27kip1 expression. Stage and grade show prognostic value as expected in G - J.
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