Tumor necrosis is associated with increased alphavbeta3 integrin expression and poor prognosis in nodular cutaneous melanomas

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis and apoptotic activity are considered important in cancer progression, but these features have not been much studied in melanomas. Our hypothesis was that rapid growth in cutaneous melanomas of the vertical growth phase might lead to tissue hypoxia, alterations in apoptotic activity and tumor necrosis. We proposed that these tumor characteristics might be associated with changes in expression of cell adhesion proteins leading to increased invasive capacity and reduced patient survival.</p> <p>Methods</p> <p>A well characterized series of nodular melanoma (originally 202 cases) and other benign and malignant melanocytic tumors (109 cases) were examined for the presence of necrosis, apoptotic activity (TUNEL assay), immunohistochemical expression of hypoxia markers (HIF-1 α, CAIX, TNF-α, Apaf-1) and cell adhesion proteins (α_vβ₃integrin, CD44/HCAM and osteopontin). We hypothesized that tumor hypoxia and necrosis might be associated with increased invasiveness in melanoma through alterations of tumor cell adhesion proteins.</p> <p>Results</p> <p>Necrosis was present in 29% of nodular melanomas and was associated with increased tumor thickness, tumor ulceration, vascular invasion, higher tumor proliferation and apoptotic index, increased expression of α_vβ₃integrin and poor patient outcome by multivariate analysis. Tumor cell apoptosis did also correlate with reduced patient survival. Expression of TNF-α and Apaf-1 was significantly associated with tumor thickness, and osteopontin expression correlated with increased tumor cell proliferation (Ki-67).</p> <p>Conclusion</p> <p>Tumor necrosis and apoptotic activity are important features of melanoma progression and prognosis, at least partly through alterations in cell adhesion molecules such as increased α_vβ₃integrin expression, revealing potentially important targets for new therapeutic approaches to be further explored.</p

Explorations on The Makran Coast, Pakistan: A Search For Paradise

In this global community, where travel to and from countries outside America is becoming more frequent, it is increasingly likely that doctors will be seeing patients with diseases that would otherwise not be common in their country. This symposium is designed to; introduce five systemic infections that can have devastating consequences for the patient and their vision.; Each presenter will highlight a challenging case from their practice, they will update us on the current thoughts of how to diagnose,; investigate and manage that infection. Neuroradiology interpretation will be provided by Dr. Chavda. In the closing minutes of their; presentation there will be comments to the future and anticipation of any changes that we can expect in the coming years for the; infectious disease described. There will be ample time for questions and reflections from the floor after each presentation.; At the conclusion of this course, the attendees should be able to: 1) recognize and distinguish five common infectious diseases that; affect the central nervous system and eye; 2) plan an appropriate series of investigations and evaluate the results regarding such; diseases and; 3) recommend treatment plans for these diseases