Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 mm biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well- established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p< 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.

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