Can Gene Expression Profiling Identify Primary Melanomas That Are Likely To Metastasize to Lymph Nodes?
Stephen S Koh, Xinmin Li, Alistair J Cochran, Scott W Binder. UCLA, Los Angeles, CA
Background: Understanding of molecular mechanisms of metastasis in melanoma is limited, leading to ineffective treatment. Of primary melanomas, 20% spread to lymph nodes (LN) at time of biopsy and may benefit from sentinel lymph node (SLN) biopsy and completion LN dissection. The other 80% will not benefit and are at risk for surgery related morbidity. We propose to study primary cutaneous melanomas to identify gene expression signatures that distinguish primary melanomas likely to have spread to the regional (sentinel) LNs from those with a lesser risk of such metastases. We aim to separate patients likely to have SLN metastases for which immediate nodal surgery has potential benefits from the majority who, may be spared unnecessary nodal surgery.
Design: 10 primary melanomas were retrieved from UCLA FFPE block archives and cells grossly dissected. 5 cases were from SLN+ patients and remaining 5 from SLN- patients. Total mRNA was isolated, amplified and labeled using and Ambion Recover All ™ Total Nucleic Acid Isolation kit, Nu-Gen WT-Ovation ® FFPE RNA Amplification system and FL-Ovation ® cDNA Biotin Module V2, respectively. Samples were hybridized to the Affymetrix Gene Chip ® Human U133 Plus 2.0 Array. Data analysis was performed using Partek ® Genomics Suite Version 6.4. Differently expressed genes were selected at >= 2-fold and p < 0.05.
Results: Hierarchical clustering of the melanocytic lesions disclosed two distinct groups: 5 primary melanomas from SLN+ patients and 5 from SLN- patients. Gene expression analysis identified statistically significant genes that were differentially expressed. Most differences were associated with increased expression that correlated with lymphatic invasion. The reverse (decreased genes) was less frequent. Some genes that were relatively increased were biologically known to be involved in migration and invasion; PHPT1, TMEM163, ATP2A2, and ADAMTS10.
Conclusions: Differential gene expression patterns distinguished primary melanomas of SLN+ patients from SLN- patients. From a list of statistically significant genes, there was a trend of relatively increased expression that correlated with positive nodal status. This initial study show that critical genes are differentially expressed and may help identify genes responsible for lymphatic invasion. Furthermore, results shown may lead us to predict and identify which patients may need nodal sampling vs. those that may not based on the molecular profiling of primary biopsied lesion. Such advancements may contribute towards reduced unnecessary surgical procedures/morbidity, and overall medical costs.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 66, Monday Morning