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

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

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

Kaplan-Meier analysis of survival in patients with or without IMP-3 expression in relation to thickness.

<p>The <i>P</i> value was obtained from comparison of four groups (log rank test). Patient with tumor thickness ≤ 4.0 mm and negative IMP-3 expression had the best 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><0.001, <i>P</i><0.001, <i>P</i><0.001, and <i>P</i> = 0.001, respectively).</p

Demographic and clinical characteristics of the study participants.

Demographic and clinical characteristics of the study participants.</p

Histogram and density plot of visual analogue scale score of pruritus intensity in the study population (n = 85).

The density of vertical axis represents the percentage of study participants.</p

Multivariable linear regression analysis of the determinants of visual analogue scale scores of pruritus intensity.

Multivariable linear regression analysis of the determinants of visual analogue scale scores of pruritus intensity.</p

Multivariable Cox proportional hazards model for the composite endpoint of technique failure or all-cause death.

Multivariable Cox proportional hazards model for the composite endpoint of technique failure or all-cause death.</p

Demographic and clinical characteristics of participants with and without pruritus.

Demographic and clinical characteristics of participants with and without pruritus.</p

The generalized additive model plot of the relationship between weekly total Kt/V and the visual analogue scale (VAS) score of pruritus intensity.

The model of the plot is adjusted for duration of dialysis, normalized protein nitrogen appearance, age, high-sensitivity C-reactive protein, total cholesterol, and intact parathyroid hormone. The little vertical bars on the horizontal axis display the distribution of individual observations. The plot indicates that a weekly total Kt/V < 1.88 is associated with the aggravation of pruritus intensity.</p