The Expression of the Hypoxia Markers CA9 and CXCR4 Is Correlated with Survival in Patients with Neuroendocrine Tumours of the Ileum

Background/Aim: The hypoxia-inducible factor pathway regulates the expression of a diverse group of molecules such as CA9 and CXCR4. Our aim was to investigate the expression of these markers in a series of patients with an ileal neuroendocrine tumour (IET) at various stages of tumorigenesis. Methods: The immunohistochemical expression of CA9 and CXCR4 was examined in 51 patients with a resected IET. A 'hypoxic score' was calculated, integrating the expression of both CA9 and CXCR4 (hypoxic score 0: absence of expression of both molecules; hypoxic score 1: expression of CXCR4 and/or CA9). Results were compared to histoprognostic factors (including tumour size, stage and grade, WHO and TNM classifications, presence of vascular or perineural invasion, presence of a fibrotic stroma and microvascular density) and to survival. Results: All tumours were well differentiated. 69% of tumours were less than 25 mm. 46% of tumours largely infiltrated the intestinal wall (>= T3, subserosa and serosa) and 90% were classified as N1 and/or 63% as M1. 57% of tumours were of grade G1, 43% of grade G2. Grade G2 (p = 0.004) and larger tumour infiltration (>= T4; p = 0.03) correlated with lower survival. Hypoxic score 1 correlated with a greater tumour size (p = 0.034), larger tumour infiltration (T3 or T4; p = 0.001), grade G2 (p = 0.046), presence of lymph node metastasis (p = 0.0066) and with lower survival of patients (p = 0.03). Conclusion: The hypoxia-inducible factors CA9 and CXCR4 were found associated to the malignant progression of neuroendocrine tumours of the ileum. Their expression may reflect higher tumour aggressivity. Copyright (C) 2011 S. Karger AG, Basel