title: Immunohistochemical expression and prognostic significance of HIF-1α and VEGF-C in neuroendocrine breast cancer.
abstract: OBJECTIVE
  To determine the predictive value of HIF-1α and VEGF-C in primary neuroendocrine breast cancers (NEBC) and their correlation with other clinico-pathological characteristics of NEBC.
  
  
  METHODS
  HIF-1α and VEGF-C were determined immunohistochemically in tissue samples from 31 cases of NEBC.
  
  
  RESULTS
  The HIF-1α expression in NEBC was predominantly negative, with only 5 (16.1%) cases showing strong reaction to HIF-1α. Eighteen (58.0%) NEBC cases showed moderate-to-strong VEGF-C expression. VEGF-C expression negatively correlated with progesterone receptor positivity (p=0.014) and duration of follow-up (p=0.021). A multivariate Cox proportional hazard regression analysis showed that HIF-1α (p=0.019) was a significant predictor of disease-free survival, whereas VEGF-C (p=0.099) showed no such association.
  
  
  CONCLUSIONS
  HIF-1α overexpression indicated unfavourable prognosis and could serve as an additional prognostic factor in NEBC. Moreover, patients with NEBC exhibiting moderate or strong VEGF-C expression could be candidates for a specific VEGF-C antibody therapy.
authors.affiliation: Clinic for Gynaecology and Obstetrics, Sveti Duh University Hospital, Sveti Duh 64, 10 000 Zagreb, Croatia. ingridmarton@gmail.com
authors.forename: Ingrid
authors.initials: I
authors.lastname: Marton
authors.forename: Fabijan
authors.initials: F
authors.lastname: Knezevic
authors.forename: Snjezana
authors.initials: S
authors.lastname: Ramic
authors.forename: Milan
authors.initials: M
authors.lastname: Milosevic
authors.forename: Davor
authors.initials: D
authors.lastname: Tomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042582:Vascular Endothelial Growth Factor C