Clinicopathological features and prognosis of patients with de novo versus nevus-associated melanoma in Taiwan

<div><p>Studies surveying melanomas associated with melanocytic nevi in Asia are rare. In this study, we examined whether nevus-associated melanomas differ from de novo melanomas in terms of their associations with clinical factors, histologic characteristics, and patient survival in Taiwan. Using data on cancer cases obtained from the Department of Pathology archives and the Cancer Registry of National Taiwan University Hospital, we conducted a retrospective analysis of 103 consecutive melanoma patients who were diagnosed between 2010 and 2015 and received follow-up through November 2016. Approximately 17.5% of the melanomas in question were associated with a nevus. In patients under 65 years of age, non-acral lentiginous melanomas were significantly associated with a higher percentage of nevus-associated melanomas. The superficial spreading subtype, younger patient age, thinner tumor, intermittent solar exposure, and early stage were significant predictors of a melanoma being histologically associated with a nevus. The appearance of a nevus associated with a melanoma predicted better recurrence-free survival compared with de novo melanomas. Although acral lentiginous melanomas (70.9%) constituted the most common histologic subtype, only 9.6% of the acral lentiginous melanomas were associated with a nevus. Furthermore, there was no statistically significant difference between the nevus-associated and de novo acral lentiginous melanomas with regard to clinicopathological factors and survival. In conclusion, nevus-associated melanomas were uncommon among acral lentiginous melanomas. Relatedly, because over half of all melanomas in Asians are acral lentiginous melanomas, Asians are less likely than Caucasians to have nevus-associated melanomas.</p></div

Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma

<div><p>Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (<i>P</i> = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (<i>P</i> = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35–9.97, <i>P</i> = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.</p></div

Wound healing rates on (a) acute burn model (b) excision wound model and the photographs of wound appearance on day 5 after (c) acute burn injury and (d) excision injury.

<p>The rate of infected wound healing was compared in animals treated with staphylococcus only (Staph), staphylococcus and NSP (Staph+NSP), staphylococcus and Poly-Ag (Staph+Poly-Ag), staphylococcus and AgNP/NSP (Staph+AgNP/NSP), staphylococcus and Aquacel® (Staph+AQ), staphylococcus and silver sulfadiazine (Staph+SS), and control (untreated). The results are expressed as the mean ± SD from three independent experiments in each group. *<i>P</i><0.05, comparison between AgNP/NSP and the other 6 groups at each time point; † <i>P</i><0.05, comparison between SS treatment with the untreated, Staph, Staph+NSP, and Staph+Poly-Ag groups; ‡ <i>P</i><0.05, comparison between AQ treatment with the untreated, Staph, Staph+NSP, and Staph+Poly-Ag groups; # <i>P</i><0.05, comparison between NSP treatment with untreated, Staph and Staph+Poly-Ag groups; § <i>P</i><0.05, comparison between Poly-Ag treatment with untreated and Staph groups. All the comparisons were confirmed by Student’s <i>t</i> test.</p

Clinical and histologic characteristics in acral lentigious melanomas.

<p>Clinical and histologic characteristics in acral lentigious melanomas.</p

Cytokine profile of wound healing.

<p>Serum levels of VEGF-A, TGF-β1 and IL-6 from mice of different treatment groups in both acute thermal injury at day 7 and excision wound at day 15 were examined by ELISA method.</p><p>Results are expressed as the mean (pg/ml) ± standard deviation (SD) from three independent experiments of each group.</p>*<p>Statistically significant as compared to the Staph group (<i>P</i><0.01, Student’s <i>t</i> test).</p

IMP-3 was expressed in ALM and associated with its progression.

<p>(<b>A</b>) Benign melanocytic nevi such as intradermal nevus were negative for IMP-3. (<b>B</b>) Focal IMP-3 expression was found in ALM with thickness ≤ 4 mm (Breslow thickness = 1.2 mm). (<b>C</b>) Strong and diffuse cytoplasmic expression was noted in ALM with depth >4.0mm (Breslow thickness = 6 mm). <b>(D</b>) Metastatic melanoma expressed IMP-3 in most tumor cells (Bar, 100 μm).</p

mRNA levels of <i>VEGF-A, TGF-β1</i> and <i>IL-6</i> in different treatment groups during wound healing.

<p>AgNP/NSP treatment also modulates the expression of cytokine mRNAs in wounded skin. The levels of <i>VEGF-A</i>, <i>TGF-β1</i> and <i>IL-6</i> mRNA expression from mice of different treatment groups in both acute thermal injury at day 7 (a) and excision wound at day 15 (b) were examined by RT-PCR. Relative band intensities of different groups were calculated by a densitometer and are demonstrated by the values under the bands. The data shown are representative of three independent experiments.</p

Univariate and multivariate analysis of risk factors associated with overall survival.

<p>Univariate and multivariate analysis of risk factors associated with overall survival.</p

Kaplan-Meier curves of survival for 73 patients with primary acral lentiginous melanomas.

<p>No overall (A), distant metastasis-free survival (B), and recurrence-free survival (C) differences were found between patients with de novo and nevus-associated acral lentiginous melanomas (<i>p</i> = 0.168, 0.159, and 0.091, respectively, log rank test).</p

Kaplan-Meier curves of survival associated with IMP-3 expression in 93 primary ALMs.

<p>IMP-3 overexpression was significantly associated with overall (<b>A</b>), melanoma-specific (<b>B</b>), recurrence-free (<b>C</b>), and distant metastasis-free survival (<b>D</b>) (<i>P</i> = 0.002, 0.006, 0.008 and 0.012, respectively; log rank test).</p