Expression of EZH2 and ALDH1 in Metastatic Malignant Melanoma Affects Survival.
Maria B Queenan, Jonathan Brody, Magdalena Potoczek, Adam Berger, Charalambos Solomides, Peter McCue, Agnieszka K Witkiewicz. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Aldehyde dehydrogenase 1 (ALDH1) and enhancer of zeste homolog 2 (EZH2) are two markers important in normal progenitor stem cells. ALDH1 is a detoxifying enzyme that may have a role in the early differentiation of stem cells, through its role in oxidizing retinol to retinoic acid. A polycomb group protein, EZH2 regulates the G2 to mitosis transition and increased cell proliferation. ALDH1 and EZH2 have been linked to the progression of many human cancers, specifically breast and prostate cancer. To date, there is no study addressing the clinical significance of ALDH1 and EZH2 expression in primary versus metastatic malignant melanoma (MM).
Design: Our study consisted of 31 cases of MM: 12 with lymph nodes metastasis and short-term survival, 8 with lymph node metastases and long-term survival and 11 primary MMs. All cases were stained for ALDH1 (BD Biosciences)and EZH2 (BD Biosciences). EZH2 expression in the melanocytes was quantified by automated image analysis (Aperio) using a 3 point scale, 0=no staining, 1=weak (<25% cells staining ), 2=moderate (25-75% cells staining) and 3=strong (>75% cells staining). Scores of 0 and 1 were considered low expression and 2 and 3 high expression. For ADH1 staining intensity (weak, strong) and precentage of staining melanocytes were evaluated. Correlation between marker expression and survival was evaluated using the Log Rank test.
Results: Primary MMs with high expression of EZH2 had shorter survival than those with low expression (p=0.0330). The median survival length for primary MMs with high EZH2 expression was 317 days as compared to 2262 days for those with low EZH2. The median survival length for patients with lymph node metastases was 201 days for those with high EZH2 and 4288 for those with low EXH2 expression (p<0.0001). ALDH1 expression was not associated with a difference in survival.
Conclusions: High expression of EZH2 in primary malignant melanomas and lymph node metastases correlates with poor survival. Our study opens the field to further investigate EZH2 utility as a biomarker of poor prognosis in MM.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 106, Tuesday Morning