title: The expression of the hypoxia markers CA9 and CXCR4 is correlated with survival in patients with neuroendocrine tumours of the ileum.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: Service d'Anatomie Pathologique, CRB3-INSERM U773, Hôpital Beaujon, Clichy, France.
authors: Lydia
authors: L
authors: Deschamps
authors: Dhouha
authors: D
authors: Bacha
authors: Vinciane
authors: V
authors: Rebours
authors: Mouniya
authors: M
authors: Mebarki
authors: Frédéric
authors: F
authors: Bretagnol
authors: Yves
authors: Y
authors: Panis
authors: Pierre
authors: P
authors: Bedossa
authors: Philippe
authors: P
authors: Ruszniewski
authors: Anne
authors: A
authors: Couvelard
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007078:Ileal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D017741:Survivors
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; C527276:CXCR4 protein, human; D019394:Ki-67 Antigen; D019718:Receptors, CXCR4; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases