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Hu antigen R (HuR) heterogeneous expression quantification as a prognostic marker of melanoma
Author(s) -
Liaudet Nicolas,
Fernandez Marylise,
Fontao Lionel,
Kaya Gürkan,
Merat Rastine
Publication year - 2018
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.13119
Subject(s) - immunohistochemistry , breslow thickness , melanoma , predictive marker , medicine , oncology , pathology , stage (stratigraphy) , antigen , cancer research , biology , cancer , immunology , sentinel lymph node , paleontology , breast cancer
Background Prognostic markers for melanoma, particularly for stage II disease, are needed for the risk‐benefit evaluation of future adjuvant therapies. The mainly nuclear RNA‐binding protein human antigen R (HuR) regulates the protein expression of thousands of mRNAs, its own heterogeneous expression could therefore reflect tumor heterogeneity and plasticity. Here, we evaluate its quantification in primary melanoma as a marker of metastatic outcome. Methods We conducted an immunohistochemistry‐based automated quantification of HuR nuclear expression heterogeneity in primary melanomas, most with Breslow thickness ≥ 1 mm and calculated the dimensionless fourth moment, that is, the kurtosis of HuR (HuR K) expression distribution. Twelve tumors from patients with no metastatic disease were compared to a similar number of tumors from patients who had metastatic disease at 2 years follow up. Results HuR K value appeared significantly higher in the non‐metastatic group comparatively to the metastatic group ( P = 2.84 × 10 −3 , 1‐tailed Wilcoxon rank‐sum test). Moreover, compared to the Breslow thickness, HuR K value appeared as a more robust marker of metastatic outcome (respective areas under receiver operating characteristic curves 0.84 and 0.87). Conclusion Our data need confirmation on a large cohort, however strongly suggest that HuR expression heterogeneity quantification using kurtosis, could be used as a prognostic marker in melanoma.