In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

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.

No abstract

No abstract

Abstract. c-Met is responsible for cell motility and tumour spreading. c-Met expression and signal transducers reflecting c-Met functionality were investigated in breast carcinomas, in correlation with patient outcome and tumour vasculature. Tissue microarrays of 930 breast carcinomas were constructed, categorised according to patients' follow-up (4-to 10-year follow-up; median, 6.5 years). Standardised immunocytochemical procedures were performed using anti-c-Met, -PI3K, -FAK, -JAK, and -CD146, -FYN and an automated autostainer (Ventana). High-throughput densitometry measuring the extent of immunoprecipitates was assessed by image analysis (SAMBA). c-Met overexpression correlated with poor survival along with PI3K and FAK reflecting c-Met functionality and CD146 and FYN expression in endothelial cells. Automated quantification of immunocytochemical precipitates using image analysis was shown to provide an objective means of measuring cellular proteins that are potentially relevant for current practice in pathological diagnosis and for specific therapy combining inhibitors of both c-Met and downstream transducer pathways, and of tumour angiogenesis.