c-Met overexpression in inflammatory breast carcinomas: automated quantification on tissue microarrays.

Inflammatory breast carcinoma (IBC) is a rare but aggressive tumour associated with poor outcome owing to early metastases. Increased expression of c-Met protein correlates with reduced survival and high metastatic risk in human cancers including breast carcinomas and is targetable by specific drugs, that could potentially improve the prognosis. In the present study, we compared c-Met expression in IBC (n=41) and non-IBC (n=480) immunohistochemically (Ventana Benchmark autostainer) in two tissue microarrays (TMA) along with PI3K and E-cadherin. The results were quantified through an automated image analysis device (SAMBA Technologies). We observed that (i) c-Met was significantly overexpressed in IBC as compared with non-IBC (P<0.001), (ii) PI3K was overexpressed (P<0.001) in IBC, suggesting that the overexpressed c-Met is functionally active at least through the PI3K signal transduction pathway; and (iii) E-cadherin was paradoxically also overexpressed in IBC. We concluded that overexpressed c-Met in IBC constitutes a potential target for specific therapy for the management of patients with poor-outcome tumours such as IBC. Automated image analysis of TMA proved to be a valuable tool for high-throughput immunohistochemical quantification of the expression of intratumorous protein markers.

[The immunohistochemical expression of CD105 is a marker for high metastatic risk and worse prognosis in breast cancers]. / L'expression immunohistochimique du CD105 est un marqueur de risque métastatique élevé et de mauvais pronostic dans les cancers du sein.

The quantification of angiogenesis in human solid tumors has been shown to be an indicator of prognosis and tumor microvasculature is a candidate target for antiangiogenic therapy. CD105 (endoglin) is significantly expressed in activated endothelial cells in culture and in tumor microvessels. Quantification of CD105 immunocytochemical expression that may be of significant clinical relevance, has not been accurately evaluated as yet. In the present report, CD105 expression on frozen sections was investigated using immunohistochemical assays in a series of 929 patients and correlated with long-term (median = 11.3 years) follow-up. The CD105 immunostaining was observed on endothelial cells mostly in small cells. The number of vessels and the immunostained surface were evaluated in so called "hot spots" within tumor stroma. Both the number of vessels and immunostained surface were correlated to the patients' outcome (overall survival, disease free survival, metastases) in the whole group of patients and also specifically in node negative subgroup. Univariate (Kaplan Meier) analysis showed that the number of CD105 positive microvessels (cut-off n = 15) was significantly correlated with poor overall survival, among all patients (p = 0.001). This correlation was less significant in the group of node negative patients (p = 0.035). Marked CD105 expression was also correlated with high metastasis risk among all patients (p = 0.006) and among node negative patients as well (p = 0.001). In multivariate analysis (Cox model) CD105 immunodetection was identified as an independent prognostic indicator. Our results suggest that CD105 immunohistochemical expression has a practical clinical relevance for identifying node negative patients with poor prognosis. Moreover, the CD105 immunodetection may also be considered as a potential tool for selecting patients that could benefit from specific antiangiogenic therapy, using anti CD105 conjugates.