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

Clinical and histologic characteristics in acral lentigious melanomas.

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

Clinical and histologic characteristics.

<p>Clinical and histologic characteristics.</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

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

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

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

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

Overexpressing KRAS by another KRAS overexpression vector (G12V) in KRAS wild-type CRC cells leads to oxaliplatin sensitivity and ERCC1 downregulation.

<p>(A) KRAS^G12V-DDK-myc-COLO320DM cells were more sensitive to oxaliplatin, but have the same sensitivity to irinotecan, 5FU, and doxorubicin than parental COLO320DM cells, as demonstrated by MTT assay. (B) The protein level of ERCC1, but not those of TOPO1 or TS, was downregulated after COLO320DM cells were transfected by the KRAS^G12V mutant vector. (C) The mRNA level of ERCC1, but not those of TOPO1 or TS, was downregulated after COLO320DM cells were transfected by the KRAS^G12V mutant vector. **: <i>p</i><0.01. (D) Increased percentage of apoptosis, from 22.5%±0.2% to 39.1%±0.2% of apoptosis (P<0.001), has been demonstrated when KRAS^wt-DDK-myc-COLO320DM cells, were compared to KRAS^G12V-DDK-myc-COLO320DM cells, in which, both were treated by the same concentration of oxaliplatin in 5 µM. *: <i>p</i><0.001.</p