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

Formaldehyde Exposure and Lower Respiratory Infections in Infants: Findings from the PARIS Cohort Study

Background: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain

Evaluation of the Water Film Weber Number in Glaze Icing Scaling

Icing scaling tests were performed in the NASA Glenn Icing Research Tunnel to evaluate a new scaling method, developed and proposed by Feo for glaze icing, in which the scale liquid water content and velocity were found by matching reference and scale values of the nondimensional water-film thickness expression and the film Weber number. For comparison purpose, tests were also conducted using the constant We(sub L) method for velocity scaling. The reference tests used a full-span, fiberglass, 91.4-cm-chord NACA 0012 model with velocities of 76 and 100 knot and MVD sizes of 150 and 195 microns. Scale-to-reference model size ratio was 1:2.6. All tests were made at 0deg AOA. Results will be presented for stagnation point freezing fractions of 0.3 and 0.5

Hypoxia inducible factor 1α gene (HIF-1α) splice variants: potential prognostic biomarkers in breast cancer

<p>Abstract</p> <p>Background</p> <p>Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.</p> <p>Methods</p> <p>Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total <it>HIF-1α </it>and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers <it>HIF-1α </it>splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.</p> <p>Results</p> <p><it>HIF-1α </it>isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated <it>HIF-1α</it>^<it>TAG</it>) and <it>HIF-1α</it>^{<it>736 </it>}mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (<it>P </it>= 0.009 and <it>P </it>= 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels (<it>P </it>= 0.037). Significant statistical association was found between tumour grade and <it>HIF-1α</it>^{<it>TAG </it>}(<it>P </it>= 0.048), and total <it>HIF-1α </it>(<it>P </it>= 0.048) mRNA levels. <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (<it>P </it>= 0.005 and <it>P </it>= 0.033 respectively). Univariate analysis showed that high <it>HIF-1α</it>^{<it>TAG </it>}mRNA levels correlated with shortened metastasis free survival (<it>P </it>= 0.01).</p> <p>Conclusions</p> <p>Our results show for the first time that mRNA expression of a <it>HIF-1α</it>^{<it>TAG </it>}splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.</p> <p>See commentary: <url>http://www.biomedcentral.com/1741-7015/8/45</url></p

Vascular grading of angiogenesis: prognostic significance in breast cancer

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (κ = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P< 0.0001), node-negative patients (P< 0.0001) and node-positive patients (P< 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P< 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer. © 2000 Cancer Research Campaig