Hypoxia-inducible factor-1a (HIF-1a) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF-1a protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF-1a expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1a expression on prognosis in a large series (n = 745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1a expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1a expression (cutoff = 10%) significantly correlated with poor overall survival ( p = 0.019). HIF-1a expression correlated with high metastasis risk among the whole group of patients ( p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1a predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1a expression was also significantly predictive of metastasis risk ( p = 0.03) and of relapse (p = 0.035). All the data suggest that HIF-1a is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1a immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1a pathway. ' 2005 Wiley-Liss, Inc.

Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a 35 S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

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Conservative surgery for patients with EOC could be considered in young patients with stage IA G1 disease. This procedure should not be performed in patients with FIGO stage > IA.