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MicroRNAs (miRNAs) have been validated as critical regulators in the development of melanoma. miR-140 was abnormally downregulated in uveal melanoma samples. However, the expression level and roles of miR-140-5p remain unclear in melanoma for now. We speculate that miR-140-5p is abnormally expressed and may play an important role in melanoma. The expressions of miR-140-5p and SOX4 messenger RNA were determined by quantitative real-time polymerase chain reaction assays. Western blot assays were employed to detect the expression levels of SOX4, Ki67, MMP-2, MMP-7, p-β-catenin, c-Myc, cyclin D1, p65, and IκBα. Luciferase reporter assays were employed to elucidate the interaction between SOX4 and miR-140-5p. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) and transwell invasion assays were applied to evaluate capabilities of cell proliferation and invasion, respectively. Xenograft models of melanoma were established to verify the role and molecular basis of miR-140-5p. Immunohistochemical (IHC) assays were employed to measure the Ki67 and SOX4 at the protein level in xenografted melanoma tissues. Herein, these observations showed that, miR-140-5p was abnormally downregulated in melanoma tissues and cells, while SOX4 was upregulated. miR-140-5p directly targeted SOX4 and inhibited its expression in melanoma cells. miR-140-5p overexpression repressed melanoma cell proliferation and invasion and its effects were partially restored SOX4 overexpression. Moreover, miR-140-5p hindered melanoma growth in vivo by downregulating SOX4. Mechanistically, miR-140-5p suppressed activation of the Wnt/β-catenin and NF-κB pathways by targeting SOX4. Our study concluded that miR-140-5p hindered cell proliferation, invasion, and tumorigenesis by targeting SOX4 via inactivation of the Wnt/β-catenin and NF-κB signaling pathways in malignant melanoma, which provides an underlying molecular mechanism for the treatment for melanoma with miRNAs., (© 2019 Wiley Periodicals, Inc.)

Background: Spitz nevi, atypical Spitz tumors and spitzoid melanomas ('spitzoid lesions') represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists., Methods: We describe use of Spitz-related terminology using data from the Melanoma Pathology (M-Path) study database comprising pathologists' interpretations of biopsy slides, a nation-wide study evaluating practicing US pathologists' (N = 187) diagnoses of melanocytic lesions (8976 independent diagnostic assessments on 240 total test cases, with 1 slide per case)., Results: Most pathologists (90%) used the Spitz-related terminology. However, significant variation exists in which specific lesions were diagnosed as spitzoid and in the corresponding treatment recommendations. Recommendations ranged from 'no further treatment' to 'wide excision of 10 mm or greater' with no category capturing more than 50% of responses. For spitzoid melanoma diagnoses, 90% of pathologists recommended excision with ≥10 mm margin. Pathologists report less confidence in diagnosing these lesions compared with other melanocytic proliferations and are more likely to request second opinions and additional clinical information (all p < 0.05)., Conclusions: Spitzoid lesions are often not classified in any standardized way, evoke uncertainty in diagnosis by pathologists, and elicit variability in treatment recommendations., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The extent of variability in treatment suggestions for melanocytic lesions made by pathologists is unknown., Objective: We investigated how often pathologists rendered suggestions, reasons for providing suggestions, and concordance with national guidelines., Methods: We conducted a cross-sectional survey of pathologists. Data included physician characteristics, experience, and treatment recommendation practices., Results: Of 301 pathologists, 207 (69%) from 10 states (California, Connecticut, Hawaii, Iowa, Kentucky, Louisiana, New Jersey, New Mexico, Utah, and Washington) enrolled. In all, 15% and 7% reported never and always including suggestions, respectively. Reasons for offering suggestions included improved care (79%), clarification (68%), and legal liability (39%). Reasons for not offering suggestions included referring physician preference (48%), lack of clinical information (44%), and expertise (29%). Training and caseload were associated with offering suggestions (P < .05). Physician suggestions were most consistent for mild/moderate dysplastic nevi and melanoma. For melanoma in situ, 18 (9%) and 32 (15%) pathologists made suggestions that undertreated or overtreated lesions based on National Comprehensive Cancer Network (NCCN) guidelines, respectively. For invasive melanoma, 14 (7%) pathologists made treatment suggestions that undertreated lesions based on NCCN guidelines., Limitations: Treatment suggestions were self-reported., Conclusions: Pathologists made recommendations ranging in consistency. These findings may inform efforts to reduce treatment variability and optimize patterns of care delivery for patients., Competing Interests: Dr. Lott is an employee of Bayer HealthCare Pharmaceuticals, which had no involvement in this research., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care., Objective: We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions., Methods: Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated., Results: Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91., Limitations: This was a small sample size of experienced pathologists in a testing situation., Conclusion: Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Backgrounds: The diagnosis of melanoma can be challenging, especially in lesions for which the histopathologic criteria bridge two or more taxonomic categories. Newer genomic analytical methods of fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have been introduced as ancillary techniques to differentiate benign and malignant melanocytic proliferations., Methods: We evaluated how pathologists perceive and are incorporating these new cytogenetic testing technologies into their practices. We conducted a study of 207 U.S. pathologists who interpret melanocytic lesions in clinical practice in 10 SEER states. Pathologists were surveyed regarding perceptions and utilization of FISH and/or CGH in their clinical practices., Results: Results showed that 38% of pathologists use FISH and/or CGH in interpreting melanocytic lesions. Pathologists reporting FISH and/or CGH use were significantly younger (p < 0.05), were fellowship trained or board certified in dermatopathology (p < 0.001) and were affiliated with an academic institute (p < 0.001). Pathologists reporting that their colleagues consider them an expert in the assessment of melanocytic lesions were more likely to employ FISH and/or CGH in their practices than non-experts., Conclusions: Early users of cytogenetic testing technologies in cutaneous pathology are more likely to be younger, affiliated with an academic institution and fellowship trained or board certified in dermatopathology., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)