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A PTEN deficiency leads to the activation of phospho‐Akt at serine 473 (p‐Akt) and promotes the tumorigenesis of melanomas by coupling with NUAK2 amplification. We tested the prognostic impact of p‐Akt and/or NUAK2 expression on the relapse‐free survival (RFS) and overall survival (OS) of melanoma patients. Primary tumors from patients with acral melanomas (112), Low‐cumulative sun damage (CSD) melanomas (38), and High‐CSD melanomas (18) were examined using immunohistochemistry and their prognostic significance was analyzed statistically. The expression of p‐Akt was found in 32.1%, 68.4%, and 55.6% of acral, Low‐CSD, and High‐CSD melanomas, while NUAK2 expression was found in 46.4%, 76.3%, and 50.0%, respectively. Either p‐Akt or NUAK2 expression was inversely correlated with the RFS of primary melanoma patients and acral melanoma patients (p‐Akt: p <.0001, p <.0001; NUAK2; p =.0005, p <.0001, respectively). Strikingly, multivariate analyses revealed that p‐Akt had a significant impact on RFS (Hazard ratio = 4.454; p <.0001), while NUAK2 did not. Further subset analyses revealed that p‐Akt expression had an inferior RFS of patients with acral melanomas (Hazard ratio = 4.036; p =.0005). We conclude that the expression of p‐Akt has a significant impact on RFS of patients with primary melanomas and can predict the relapse of patients with acral melanomas. Research Highlights: The expression of p‐Akt has a significant impact on relapse‐free survival in primary melanoma patients and can predict the relapse of acral melanoma patients. The expression of p‐Akt can be a promising biomarker to stratify acral melanomas for clinical trials. [ABSTRACT FROM AUTHOR]

Post‐inflammatory hyperpigmentation (PIH) is a common cutaneous condition that can cause a disfigured appearance. However, the pathophysiology of PIH remains poorly understood, at least in part, because an appropriate animal model for research has not been established. In order to analyze the pathomechanism of PIH, we successfully induced PIH in a hairless version of transgenic mice (hk14‐SCF Tg/HRM) that have a human‐type epidermis containing melanin by repeated hapten application of 2,4‐dinitrofluorobenzene. Histopathologic observation showed epidermal hyperplasia, predominant infiltrations of inflammatory cells, and melanin‐containing cells in the dermis just after elicitation of the atopic dermatitis‐like condition. At week 2, the findings were similar to the characteristics of PIH, that is, an increase of melanin without spongiosis or liquid degeneration in the epidermis and an increase in dermal melanophages. Dynamic analysis of melanin showed that the melanin in the dermis remained for a longer duration than in the epidermis. Furthermore, immunohistochemical staining revealed that the majority of cells containing melanin were positive for the anti‐CD68 antibody, but negative for the anti‐F4/80 antibody. These data suggest that novel treatments of PIH should be targeted against macrophages and should eventually lead to the development of new treatment modalities. [ABSTRACT FROM AUTHOR]

Oculocutaneous albinism (OCA) type 4 is one of the most common types of albinism among Japanese population. In some patients who were clinically diagnosed with OCA, we have found a heterozygous pathological mutation in the coding region of SLC45A2, the gene responsible for OCA4, not leading to a DNA‐based diagnosis. In this study, we evaluated pathological variants in the promoter region of SLC45A2 in these patients. The results indicated that the majority of the patients had a 4‐bp deletion in the said region (c.‐492_489delAATG; GenBank accession number: NM_016180; rs984225803) in the contralateral allele. These patients displayed a mild phenotype, especially regarding eye manifestations. The results of the luciferase reporter assay and electrophoretic mobility shift assay supported the pathological role of the variant. In addition, four of 220 alleles in Japanese normal control subjects also showed the deletion variant, indicating that this variant could possibly be a skin color‐associated variant. [ABSTRACT FROM AUTHOR]