ABSTRACT
Beyond depth of invasion, there are very few prognostic markers to predict outcome in melanoma. It has been shown recently that the beta-catenin oncogene is mutated or shows altered subcellular localization suggesting that activation of beta-catenin mediated signaling plays a role in oncogenesis. We hypothesize that assessment of activated beta-catenin, as detected by a phospho-specific antibody, may be useful to predict outcome in melanoma. We use immuno-histochemical analysis of beta-catenin and phospho-beta-catenin, first to verify the specificity of the phospho-beta-catenin antibody and then to assay expression in a tissue microarray-based study. The subcellular localization of beta-catenin is membranous in some cases and cytoplasmic and nuclear in others. We validate the specificity of a ser33/37/thr41 phospho-beta-catenin antibody in transfected cells and show that the expression is almost exclusively localized to the nucleus in both cultured cells and human tissue. Evaluation of both total and phospho-beta-catenin antibodies showed that cytoplasmic/nuclear staining was more common in primary lesions, whereas nuclear phospho-beta-catenin was more common in metastatic lesions. High levels of nuclear phospho-beta-catenin are associated with significantly worse overall survival (51% vs. 25% overall survival at 5 years, p = 0.046). These results suggest that phospho-specific antibodies to beta-catenin define a unique subset of cases and that monitoring of phospho-beta-catenin expression may be useful for assessing prognosis in malignant melanoma.
Subject(s)
Cytoskeletal Proteins/metabolism , Melanoma/metabolism , Skin Neoplasms/metabolism , Trans-Activators/metabolism , Cell Nucleus/metabolism , Female , Gene Expression , Humans , Immunoenzyme Techniques , Male , Melanoma/pathology , Middle Aged , Mutation , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , Prognosis , Skin Neoplasms/pathology , Survival Rate , Transfection , Tumor Cells, Cultured , beta CateninSubject(s)
Amyloid/ultrastructure , Colitis/complications , Colitis/pathology , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/pathology , Intestinal Mucosa/ultrastructure , Aged , Colonoscopy , Diarrhea/etiology , Diarrhea/pathology , Female , Humans , Intestinal Mucosa/pathologyABSTRACT
Replacement of the aortic arch for atheroma with cerebral embolization is in its infancy. The appropriateness of such intervention is controversial. Over a 10-month period, a 58-year-old woman suffered multiple debilitating cerebral vascular accidents manifested by motor, sensory, and memory deficits and documented by computed tomographic scanning and magnetic resonance imaging. Carotid and vertebral arteries were free of arteriosclerotic disease. Transesophageal echocardiography demonstrated two large atheromas with friable, pedunculated forms, one in the aortic arch and one in the very proximal descending thoracic aorta. Transcranial ultrasound revealed recurrent cerebral microembolic events. Cerebrovascular events continued, and the atheromas increased in size, despite treatment with Coumadin and aspirin. Under deep hypothermic arrest, the segment of the aortic arch harboring the atheroma was excised and replaced with a Dacron graft. Repeat transcranial ultrasound revealed cessation of embolic signals. All cerebrovascular events ceased. No further anticoagulation therapy was required. The patient has made substantial recovery from the preoperative deficits and continues to do well 1 year after aortic arch replacement. Resection of mobile aortic arch atheromas is likely to become increasingly important in the future as transesophageal echocardiography leads to their more common identification as a cause of cerebral ischemic events.
