An experienced dermatopathologist can reliably diagnose most cutaneous malignant melanomas based on well-established morphologic characteristics. However, in a minority of cases, traditional histopathologic evaluation and immunohistochemistry (IHC) are inadequate to confidently distinguish melanoma from benign melanocytic lesions such as Spitz nevi and dysplastic nevi. The advent of high-throughput gene expression array technology has resulted in the identification of hundreds of potential molecular diagnostic biomarkers, but no single chromosomal, DNA, RNA or protein marker has yet been shown to differentiate melanoma from nevus with sensitivity and specificity approaching 100%. We selected the protein products of 11 genesATP1B1, CYCLIN D1, DLX-1, HOXB13, LIF, MEIS2, MITF, MYC, PHACTR1, PTPRF and TWISTup-regulated in melanoma cell-culture and tissue-based expression arrays as candidate diagnostic biomarkers for preliminary investigation. Based on the results of our pilot studies, we proposed that increased expression of Phactr1 protein, as measured by IHC, could be used to differentiate malignant melanomas from nevi. We applied Phactr1 monoclonal antibody to a 480-core tissue microarray that included samples from 28 nevi and 62 primary melanomas. A simple scoring algorithm derived from this data distinguished primary melanoma from nevus in the training set with 92% sensitivity and 100% specificity. These data suggest that Phactr1 immunohistochemical staining is a potentially useful aid in the clinical diagnosis of primary cutaneous melanoma.
| Identifer | oai:union.ndltd.org:YALE_med/oai:ymtdl.med.yale.edu:etd-04222010-200934 |
| Date | 30 September 2010 |
| Creators | Trufant, Joshua William |
| Contributors | Robert Tigelaar, MD, Marcus Bosenberg, MD, PhD, Jennifer McNiff, MD |
| Publisher | Yale University |
| Source Sets | Yale Medical student MD Thesis |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://ymtdl.med.yale.edu/theses/available/etd-04222010-200934/ |
| Rights | restricted, I hereby grant to the Yale School of Medicine the non-exclusive license to photocopy, archive and make accessible, under the conditions specified below, my print and electronic thesis, in whole or in part, in all forms of media. <p> I agree that the Yale School of Medicine may electronically store, copy or translate my thesis to any medium or format for the purpose of preservation and accessibility. The Yale School of Medicine is not under obligation to reproduce or display my thesis in the same format in which it was originally deposited. <p> I retain all ownership rights to the thesis, including but not limited to the right to use in future works (such as articles and books) all or part of this thesis. |
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