ABSTRACT
Fludeoxyglucose F 18 positron emission tomography/computed tomography (PET/CT) has been invaluable in the assessment of melanoma throughout the course of the disease. As with any modality, the studies are incomplete and more information will be gleaned as our experience progresses. Additionally, it is hoped that a newer PET agent in the pipeline will give us even greater success in the identification and subsequent treatment of melanoma. This article aims to examine the utilization of PET/CT in the staging, prognostication, and follow-up of melanoma while providing the physicians who order and interpret these studies practical guidelines and interpretive pitfalls.
Subject(s)
Melanoma/diagnostic imaging , Multimodal Imaging , Skin Neoplasms/diagnostic imaging , Biomarkers, Tumor/analysis , Fluorodeoxyglucose F18 , Humans , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Melanoma/pathology , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/pathology , Neoplasm Staging , Radionuclide Imaging , Radiopharmaceuticals , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: The Odontogenic Ameloblast-associated Protein (ODAM) is expressed in a wide range of normal epithelial, and neoplastic tissues, and we have posited that ODAM serves as a novel prognostic biomarker for breast cancer and melanoma. Transfection of ODAM into breast cancer cells yields suppression of cellular growth, motility, and in vivo tumorigenicity. Herein we have extended these studies to the effects of ODAM on cultured melanoma cell lines. METHODS: The A375 and C8161 melanoma cell lines were stably transfected with ODAM and assayed for properties associated with tumorigenicity including cell growth, motility, and extracellular matrix adhesion. In addition, ODAM-transfected cells were assayed for signal transduction via AKT which promotes cell proliferation and survival in many neoplasms. RESULTS: ODAM expression in A375 and C8161 cells strongly inhibited cell growth and motility in vitro, increased cell adhesion to extracellular matrix, and yielded significant cytoskeletal/morphologic rearrangement. Furthermore, AKT activity was downregulated by ODAM expression while an increase was noted in expression of the PTEN (phosphatase and tensin homolog on chromosome 10) tumor suppressor gene, an antagonist of AKT activation. Increased PTEN in ODAM-expressing cells was associated with increases in PTEN mRNA levels and de novo protein synthesis. Silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing melanoma cells. Similar PTEN elevation and inhibition of AKT by ODAM was observed in MDA-MB-231 breast cancer cells while ODAM expression had no effect in PTEN-deficient BT-549 breast cancer cells. CONCLUSIONS: The apparent anti-neoplastic effects of ODAM in cultured melanoma and breast cancer cells are associated with increased PTEN expression, and suppression of AKT activity. This association should serve to clarify the clinical import of ODAM expression and any role it may serve as an indicator of tumor behavior.
Subject(s)
Breast Neoplasms/metabolism , Carrier Proteins/metabolism , Melanoma/metabolism , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Amyloid , Carrier Proteins/genetics , Cell Adhesion , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cytoskeleton , Gene Expression Regulation, Neoplastic , Humans , Intracellular Signaling Peptides and Proteins , Melanoma/pathology , Neoplasm Proteins , PTEN Phosphohydrolase/genetics , Phosphatidylinositol 3-Kinases/metabolism , RNA, Messenger/metabolism , TransfectionABSTRACT
Ionizing radiation has been used therapeutically for a variety of clinical conditions, including treatment of hypertrophic keloids. Keloids may rarely be associated with malignancy, but the use of low-dose ionizing radiation is associated with an increased risk of cutaneous malignancies. We describe a case in which a primary desmoplastic melanoma arose in a long-standing, previously irradiated keloid.
