Date of Award

2-14-2008

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

David L. Rimm

Abstract

Cadherin and catenin-family proteins regulate adhesion in malignant melanoma. Using AQUA (Automated Quantitative Analysis) to quantitate the levels of alpha-catenin, beta-catenin, p120-catenin, N-cadherin, E-cadherin, and P-cadherin in melanoma on tissue microarrays (TMAs), we classified 513 patients by protein expression using hierarchical clustering and regression analysis. The dendrogram supported positive correlations seen upon Spearman rho analysis of P-cadherin and beta-catenin (r=0.5238, p<0.0001) and negative, weak association of N-cadherin with other markers. Patients with high expression of N-cadherin had the highest 20-year survival rate (p=0.0003). Our adherens protein molecular classification of melanoma defines at least two distinctive sub-populations of melanoma patients, those with high expression of N-cadherin and those with low expression who have decreased survival. These findings extend previous cDNA array-based findings of an epithelioid class and neural crest class of melanomas.

Comments

This is an Open Access Thesis.

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