Aldehyde dehydrogenase 1 (ALDH1) has been proposed as biomarker of stem cells for certain human cancers.,ALDH1 expression has been correlated with poor patient outcomes in a variety of malignancies but better patient outcomes in others, and its prognostic significance in malignant melanoma is unclear.,Thus, 68 melanoma patients with comprehensive clinical and pathologic follow up data were used to construct a tissue microarray.,A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for ALDH1.,Survival time was defined as the time between diagnosis and melanoma-specific death.,Using univariate logistic regression, a low (<80 H-score) ALDH1 score showed 3.7-fold increase in risk for melanoma-specific death within 10 years when compared to high (>80) ALDH1 levels (p= 0.017).,Odds of MSD were lower by a factor of approximately 0.9 for each 10-point increase in H-Score.,Median survival time was 44.1 months and 180.9 months for patients with low and high ALDH1 expression, respectively.,Using multivariate analysis, ALDH1 H-score was found to be an independent prognostic factor.,These findings suggest that ALDH1 expression in malignant melanoma has a favorable effect on patient survival.,Further study is needed elucidate the function of this enzymatic protein in melanoma progression.
Disseminated cutaneous malignant melanoma (CMM) is commonly unresponsive to standard chemotherapies, and there are as yet no predictive markers of therapy response.,In the present study we collected fresh-frozen pretreatment lymph-node metastasis samples (n=14) from melanoma patients with differential response to dacarbazine (DTIC) or temozolomide (TMZ) chemotherapy, to identify proteins with an impact on treatment response.,We performed quantitative protein profiling using tandem mass spectrometry and compared the proteome differences between responders (R) and non-responders (NR), matched for age, gender and histopathological type of CMM.,Biological pathway analyses showed several signalling pathways differing between R vs NR, including Rho signalling.,Gene expression profiling data was available for a subset of the samples, and the results were compared with the proteomics data.,Four proteins with differential expression between R and NR were selected for technical validation by immunoblotting (ISYNA1, F13A1, CSTB and S100A13), and CSTB and S100A13 were further validated on a larger sample set by immunohistochemistry (n=48).,The calcium binding protein S100A13 was found to be significantly overexpressed in NR compared with R in all analyses performed.,Our results suggest that S100A13 is involved in CMM resistance to DTIC/TMZ.