Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma.bioinformatics ͉ human ͉ microarray ͉ metastasis ͉ laser capture I n the current staging system for cutaneous melanoma, vertical thickness of the primary tumor is the dominant prognostic factor, belying the fact that a subset of thin tumors metastasize, whereas some thick tumors do not undergo metastasis (1). The original melanoma tumor progression model is characterized by an initial radial growth phase, encompassing in situ and minimally invasive tumors (2). This phase is followed by the development of vertical growth phase, which has been postulated to be the first point at which the tumor gains metastatic capacity. However, metastasis occurs, although with decreased frequency, in patients whose primary melanoma pathology exhibits only a radial growth pattern (3). Previous transcriptome analysis in melanoma defined a cluster of genes expressed in a majority of metastatic melanomas (4); however, this cluster was not related to radial or vertical growth, and precursor nevi (moles) and primary melanomas were not examined. Likewise, mutations in B-RAF occur commonly in both nevi (5) and melanoma (6), and, thus, do not distinguish progressive stages in melanoma progression. In this study, we used cDNA expression array profiling to characterize the global patterns of transcript modulation that underlie the various phases in the known tumor progression pathway of melanoma. MethodsStudy Subjects. Samples from melanoma patients and nevus volunteers presenting to the Melanoma Center were obtained with informed consent under a protocol approved by the UCSF Institutional Review Board. After biopsy, all samples were frozen in OCT freezing medium over dry ice. Subsequently, samples were processed for hematoxylin͞eosin staining and confirmed by pathologic review. Only samples comprised of Ͼ95% tumor cells were analyzed.
International Journal of Dermatology 2005, 44 , 757-764 757 Pityriasis rosea (PR) is a mild, self-limited skin disease of unknown etiology. Viral and bacterial causes have been considered as possible causes. Pityriasis rosea typically affects children and young adults. It is characterized by an initial herald patch, followed by the development of salmon-pink scaly macules which, when localized to the trunk, form alongLanger's lines of cleavage. Pityriasis rosea may be difficult to diagnose until the appearance of these characteristic smaller secondary lesions. Several medications can cause a rash similar to PR. Pityriasis rosea must be distinguished from several diseases, including secondary syphilis. The treatment of PR is usually symptomatic. 758Education Pityriasis rosea González et al.
Sequential combination of preoperative lymphoscintigraphy and intraoperative mapping is a reliable way to identify regional SLN. The frequency of microscopic metastatic melanoma of the SLN(s) is 18.4%. Gamma-probe--guided resection minimizes the extent of lymph node dissection. Further follow-up is needed to assess the outcome of this group of patients for regional and systemic recurrences.
Since the 1940s, the number of employee benefits provided by employers and costs related to these benefits have increased dramatically. However, in the face of intensified product market competition, more and more organizations are decreasing their benefits packages as part of broader efforts to decrease labor costs. At the same time, many employees have become dependent on employer‐provided benefits to help satisfy basic security needs. This article examines the evolution of this predicament and the associated consequences that are likely to arise as a result of this conflict between worker expectations and employer practices. Ideas for resolution of this employee–employer conflict are also discussed.
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