High ALDH1 Expression Correlates with Better Patient Outcomes in Tumorigenic Malignant Melanoma
Ronnie M Abraham, Emin Tahirovic, Phyllis Gimotty, David E Elder, Patricia Van Belle, Xiaowei Xu. University of Pennsylvania, Philadelphia, PA
Background: Aldehyde dehydrogenase 1 (ALDH1) is a proposed biomarker of stem cells in certain human cancers. ALDH1 expression has been correlated with poor patient outcomes in breast cancer, but better patient outcomes in ovarian cancer, and its prognostic importance in malignant melanoma is unknown. ALDH1 expression in melanoma is studied using a tissue microarray and immunohistochemistry in a series of 68 patients with long-term follow-up.
Design: 68 tumorigenic melanoma patients from the Pigmented Lesion clinic at the University of Pennsylvania, with comprehensive clinical and pathologic data and at least 10 years of follow-up, were used to construct a tissue microarray. Three to four cores were procured from each lesion. Immunohistochemical staining for ALDH1 was performed and its expression analyzed by two independent readers (RMA, XX) using a modified histological score (H-score) based on staining percentage and intensity, with a maximum score of 300. Survival time was defined as the time between diagnosis and melanoma-specific death (MSD). Kaplan-Meier survival curves were computed for the MSD times. An H-score threshold of 80 maximizes the log-rank test statistic between two resulting ALDH1-groups.
Results: For the cohort, the median age at diagnosis was approximately 59 years and the median melanoma thickness 3.25 mm. The overall percentage of MSD within 10 years was 62%. Using univariate logistic regression, a low (<80 H-score) ALDH1 score showed 3.7-fold increase in risk for MSD within 10 years when compared to high (>80) ALDH1 levels (p= 0.017). Kaplan-Meier survival curves for the two groups based on ALDH1 expression revealed 72% of those with low ALDH expression had MSD compared to only 40% in the group with high ALDH1 expression. Median survival time was 44.1 months and 180.9 months for patients with low and high ALDH1 expression, respectively.
Conclusions: These findings suggest that ALDH1 expression in malignant melanoma has a favorable effect on patient survival, similar to findings seen in ovarian carcinoma and in contrast to findings seen in breast cancer. Further study is needed elucidate the true function of this enzymatic protein in melanoma progression.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 74, Monday Morning