Date of Award
9-30-2010
Document Type
Thesis
Degree Name
Medical Doctor (MD)
First Advisor
Robert Tigelaar, MD
Second Advisor
Marcus Bosenberg, MD, PhD
Third Advisor
Jennifer McNiff, MD
Abstract
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.
Recommended Citation
Trufant, Joshua William, "Phactr1 as a novel biomarker to distinguish malignant melanoma from nevus" (2010). Yale Medicine Thesis Digital Library. 178.
https://elischolar.library.yale.edu/ymtdl/178
Comments
This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.