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研究生:沈宜萱
研究生(外文):Yi-Shuan Sheen
論文名稱:台灣肢端型黑色素癌
論文名稱(外文):Acral Lentiginous Melanomas in Taiwan
指導教授:張逸良張逸良引用關係朱家瑜朱家瑜引用關係
指導教授(外文):Yih-Leong Chang
口試日期:2017-06-15
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:病理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:90
中文關鍵詞:黑色素癌肢端型黑色素癌預後基因變異壓力IMP-3
外文關鍵詞:acral lentiginous melanomaIMP-3melanomamutationnevusprognosisstress
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黑色素癌在亞洲人是一個少見的疾病,卻是惡性度最高的皮膚癌。黑色素癌可以發生在所有含有黑色素細胞的部位。皮膚的黑色素癌可以分成四大類:表淺蔓延性黑色素癌、結節性黑色素癌、惡性小痣性黑色素癌和肢端型黑色素癌。和白種人不同的是,肢端型黑色素癌是亞洲人最常見的一種黑色素癌。在我們的研究中,肢端型黑色素癌佔了約70%的案例。因為肢端型黑色素癌不容易發現,所以診斷時往往腫瘤已經很嚴重,預後也比較不好。目前關於亞洲的肢端型黑色素癌的研究報告並不多,如果我們的研究能找出能預測預後的基因變異、分子標記或者相關的病理與臨床特徵,相信在治療策略上可以提供患者更多的幫助。
在許多白人和少數亞洲人的黑色素癌有研究過BRAF和NRAS mutations的情形。但是關於台灣人BRAF和NRAS mutations的情形以及基因變異和臨床特徵相關性的研究很少。因此本論文先分析119位台灣人BRAF和NRAS mutations的情形以及基因變異和臨床病理特徵與預後的關係。我們發現BRAF mutations佔全部黑色素癌的14.3% (17/119),而NRAS mutations佔10.1% (12/119)。17個有BRAF mutations的病患裡,有15個(88.2%)是V600E mutations。BRAF mutations比較常發生在年輕的患者(P=0.0035)、黑色素癌的腫瘤厚度較薄(P=0.0181)與較少潰瘍(P=0.0089)。NRAS mutations比較常發生在有淋巴結轉移的病患(P=0.0332)。不過BRAF和NRAS mutations和黑色素癌的預後並沒有顯著關係。雖然BRAF和NRAS mutations在台灣人是相對少見的,但可以針對有BRAF或NRAS mutations的病人,給予適合的標靶治療。
第二型似胰島素生長因子(IGF-II) mRNA結合蛋白-3 (IMP-3)乃是IGF-II mRNA結合蛋白家族的一員。最近發現IMP-3在轉移的黑色素癌中表現高於淺層黑色素癌,而在良性黑色素痣則不表現,顯示IMP-3是一個新的黑色素癌進展標記。我們之前的研究分析皮膚黑色素癌患者腫瘤的IMP-3免疫組織化學染色,發現IMP-3高表現和肢端型黑色素癌以及晚期黑色素癌有關,而且IMP-3高表現的患者五年存活率比較低。因此我們收集了93個肢端型黑色素癌做進一步分析,發現IMP-3在75.3%的腫瘤有高表現,而且IMP-3的高表現和腫瘤厚度較厚以及晚期腫瘤有關。IMP-3高表現的病患其overall, melanoma-specific, recurrence-free和distant metastasis-free survivals都比IMP-3低表現的病患顯著的差,顯示IMP-3會增加黑色素癌的惡性度。在腫瘤厚度小於4.0 mm的病患,如果有高表現IMP-3,melanoma-specific survival會比低表現IMP-3的病患差。多變量分析發現IMP-3是肢端型黑色素癌的melanoma-specific survival的獨立預後因子。肢端型黑色素癌的病患如果能檢驗IMP-3在腫瘤的表現量,可以預期他的預後並決定最適合的治療。
在西方國家有很多痣相關黑色素癌的討論,卻很少有關於亞洲人的痣相關黑色素癌的研究。因此,我們探討台灣的痣相關黑色素癌和原發黑色素癌在臨床表現、病理特徵以及預後的差異。本研究利用台大醫院病理部病理診斷資料庫以及台大醫院癌症防治中心癌症資料庫進行統計分析,在2010-2015年間共有103位皮膚黑色素癌病患,並追蹤患者預後至2016年11月。全部103位黑色素癌病患裡,有17.5%的黑色素癌是痣相關黑色素癌。在小於65歲的病患中,非肢端型黑色素癌和痣相關黑色素癌有統計上顯著的相關性。痣相關黑色素癌常合併的臨床病理特徵有:表淺蔓延性黑色素癌、患者年紀輕、腫瘤厚度薄、間歇性陽光曝曬的部位、和早期癌症。痣相關黑色素癌的recurrence-free survival比原發黑色素癌長。雖然肢端型黑色素癌佔了全部黑色素癌的70.9%,肢端型黑色素癌裡面只有9.6%是痣相關黑色素癌。關於臨床病理特徵或者是預後的表現,原發肢端型黑色素癌和痣相關肢端型黑色素癌是沒有顯著差異的。痣相關黑色素癌在肢端型黑色素癌裡是相對少見的。因為亞洲人大部份的黑色素癌都是肢端型黑色素癌,所以和西方國家相比,亞州人比較少有痣相關黑色素癌。
肢端型黑色素癌的病理發生機轉到現在還不清楚,最近有報告提到機械應力壓迫可能與黑色素癌的形成有關。所以我們收集了台大醫院和高雄長庚醫院2000-2015年間共153位足底肢端型黑色素癌的患者來做進一步的分析。探討發生在足底不同位置的肢端型黑色素癌是否臨床病理特徵或者是預後的表現有所不同。以goodness of fit分析發現,和non-stress-bearing areas相比,stress-bearing areas比較容易產生黑色素癌(P<0.0001)。跟arch相比,rear of the foot和front of the foot是比較容易產生黑色素癌的部位,且有達到統計上顯著差異。黑色素癌分布的位置和年紀、性別、左右腳、潰瘍、細胞分裂、淋巴結轉移、腫瘤厚度、癌症分期以及預後沒有顯著相關。
隨著更加了解台灣肢端型黑色素癌的基因變異、分子機轉、病理與臨床特性,可以幫助我們在診斷、治療的選擇、預後的評估等方面給予患者更全面的資訊,提供台灣的患者一個最好的機會來治療肢端型黑色素癌。
Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. Melanomas can develop in any melanocyte-containing anatomic site. Based on WHO classification, cutaneous melanoma can be classified into four main subtypes: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, and nodular melanoma. Superficial spreading melanoma is the most common type of melanoma in the West. In Asians, superficial spreading melanoma is less common than acral lentiginous melanoma, which is the most common subtype. In our study, acral lentiginous melanomas accounted for more than 70% of the cases. Because of their typically inconspicuous locations on the body, acral lentiginous melanomas are usually not noticed until the late stages, when they are ulcerated or large in size, so they tend to have a grave prognosis. However, only a few case series of acral lentiginous melanomas has been published in Asia and knowledge on its characteristics and prognosis factors is still limited. Hence, the establishment of more clinical, pathological, genetic or molecular markers for the prediction of invasiveness and metastatic potential of acral lentiginous melanomas will aid in the development of better strategies for patient management.
BRAF and NRAS mutations have been described in melanomas among Caucasians and some Asian populations. However, few large-scale studies have investigated the status and clinical significance of BRAF and NRAS mutations in a Taiwanese population. The incidence of somatic mutations within the BRAF and NRAS genes was 14.3% (17/119 patients) and 10.1% (12/119 patients), respectively. Among the 17 patients with BRAF mutations, 15 (88.2%) had V600E mutations. BRAF mutation was frequently detected in younger patients, in thin melanomas, and in melanomas with less ulceration. The NRAS mutation was more often seen in patients with lymph node metastasis. Both BRAF and NRAS mutations were not significantly correlated with overall survival and recurrence-free survival.
IGF-2 mRNA-binding protein 3 (IMP-3) is a member of the insulin-like growth factor-II mRNA-binding protein family. In our previous study, IMP-3 expression was much stronger in advanced-stage/metastatic melanomas and correlated with poor overall survival. First, we correlated IMP-3 expression with clinicopathological parameters as well as prognosis to further dissect the role of IMP-3 in a larger cohort of acral lentiginous melanomas. 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. 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. IMP-3 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.
Statistical data regarding melanomas associated with melanocytic nevi in Asia appears to be limited, although we did discover such information with regard to populations in the West. 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. 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.
The pathogenesis of melanomas emerging in plantar surfaces remains unclear; however, mechanical stress has been reported to increase the formation of melanomas. We examined whether melanomas which developed in different areas of the patients’ soles differed in their associations with various clinicopathological characteristics and survival. Testing by goodness of fit indicated that stress-bearing areas were significantly more conducive to the generation of melanomas than non-stress-bearing areas. More specifically, compared to the arch, the rear of the foot and front of the foot were significantly more conducive to the generation of melanomas. The distribution pattern was not associated with differences in age, gender, right/left foot involvement, ulceration, mitosis, lymph node metastasis, tumor thickness, or stage. The overall, distant metastasis-free, and recurrence-free survival rates did not differ significantly between the stress-bearing and non-stress-bearing areas.
We conclude that increased understanding of the mutations, clinicopathologic factors and molecular markers of acral lentiginous melanomas will allow for dramatic improvement in the treatment strategies, providing the best chance for long-term palliation or cure of acral lentiginous melanomas in Taiwan.
口試委員會審定書…………………………………………………….............………...i
誌謝…………………………………………………………………………….…..........ii
中文摘要………………………………………………………………………..............iii
英文摘要…………………………………………………………………....…….….....vi
第一章 前言(Introduction)...……………………........................................................1
1.1 BRAF and NRAS mutations………….........................................................................3
1.2 IMP-3 expression in melanomas...………..................................................................3
1.3 Nevus-associated melanomas...……………………...................................................4
1.4 Mechanical stress and melanomas…………………...................................................5
第二章 材料與方法(Materials and Methods)……………………..............................5
2.1 Patients and tissues of the BRAF and NRAS mutations study………...……………..5
2.2 Patients and tissues of the IMP-3 study...……………………....................................5
2.3 Patients and tissues of the nevus-associated melanomas study………………...……6
2.4 Patients and tissues of the mechanical stress study………………………………….7
2.5 Immunohistochemical analysis..……………………..................................................7
2.6 Mutation analyses of BRAF, NRAS and KIT genes in melanoma tissues……………9
2.7 Statistical analysis..…………………........................................................................10
第三章 實驗結果 (Results)…………………………...................................................10
3.1 BRAF and NRAS mutations in cutaneous melanoma patients...................................10
3.2 Expression of IMP-3 protein in ALM…………...……………………………........13
3.3 Clinicopathological and prognostic significance of IMP-3 expression. …………...14
3.4 Concomitant effects of IMP-3 expression with thickness on the prognosis of ALM............................…………………………………………………………………15
3.5 IMP-3 Expression is an Independent Prognostic Factor in ALM……………….…15
3.6 Nevus-associated melanomas in Taiwan…………………………………………...16
3.7 Clinicopatholigical factors of nevus-associated melanomas………………….……17
3.8 Prognosis of nevus-associated melanomas…………………………………………17
3.9 Clinicopathological factors and prognosis of nevus-associated acral melanomas....18
3.10 Clinicopathological analysis of acral melanomas and the relevance of mechanical stress……………………………………………………………………………………18
第四章 討論 (Discussion) …………………………....................................................20
4.1 Prevalence of BRAF and NRAS mutations in melanoma patients in Taiwan……………………………………………………………………………….…21
4.2 IMP-3 expression correlates with poor prognosis in acral lentiginous melanoma…23
4.3 Clinicopathological features and prognosis of patients with de novo versus nevus-associated melanoma in Taiwan………………...................................................26
4.4 Acral melanomas and the relevance of mechanical stress.........................................29
第五章 展望 (Perspectives) ………………………......................................................31
第六章 參考文獻 (Reference) ………………………………………….....................33
第七章 附圖及說明 (Figures and figure legends) ………………………...................52
Fig 1. Kaplan-Meier curves of survival associated with mutations in 119 melanoma patients.............................................................................................................................52
Fig 2. Representative sections with immunohistochemical staining intensity against IMP-3………………………….......................................................................................53
Fig 3. IMP-3 was expressed in ALM and associated with its progression……..………54
Fig 4. Kaplan-Meier curves of survival associated with IMP-3 expression in 93 primary ALMs…………………………………………………………………….………..……55
Fig 5. Kaplan-Meier analysis of survival in patients with or without IMP-3 expression in relation to thickness…………………………............................................................56
Fig 6. Superficial spreading melanoma arising from a nevus….....................................57
Fig 7. Kaplan-Meier curves of survival for 103 primary melanoma patients………….59
Fig 8. Kaplan-Meier curves of survival for 73 patients with primary acral lentiginous melanomas………………………………………………………………………..…….60
Fig 9. Study flow diagram…………………………………………………………...…61
Fig 10. Distribution of acral melanomas in the plantar area……………………...……62
Fig 11. Distribution of 114 primary acral melanomas in the plantar area…...…………63
Fig 12. Kaplan-Meier curves of survival in 114 primary acral melanomas……………64
Fig 13. Distribution of primary acral melanomas in the palmar area……………..……65
第八章表格 (Tables) ………………………….............................................................66
Table 1. BRAF and NRAS mutations identified in 119 primary melanomas...................66
Table 2. Association of BRAF and NRAS mutation status with patient and melanoma characteristics..................................................................................................................67
Table 3. Summary of BRAF and NRAS mutation in primary cutaneous melanoma in Asians..............................................................................................................................69
Table 4. Univariate and multivariate analyses of risk factors associated with overall survival............................................................................................................................70
Table 5. Univariate and multivariate analyses of risk factors associated with recurrence-free survival ..................................................................................................70
Table 6. Clinical and histologic prognostic factors and IMP-3 expression……….……71
Table 7. Univariate and multivariate analysis of risk factors associated with melanoma-specific survival in acral lentiginous melanoma patients……….……….…73
Table 8. Univariate and multivariate analysis of risk factors associated with overall survival in acral lentiginous melanoma patients…………….………………..……..…74
Table 9. Univariate and multivariate analysis of risk factors associated with recurrence-free survival in acral lentiginous melanoma patients………………………75
Table 10. Univariate and multivariate analysis of risk factors associated with distant metastasis-free survival in acral lentiginous melanoma patients………………….……76
Table 11. Clinical and histologic characteristics in nevus-associated melanomas..........77
Table 12. Univariate and multivariate analysis of risk factors associated with overall survival…………………………....................................................................................79
Table 13. Univariate and multivariate analysis of risk factors associated with distant metastasis-free survival…………………………...........................................................80
Table 14. Univariate and multivariate analysis of risk factors associated with recurrence-free survival……………...............................................................................81
Table 15. Clinical and histologic characteristics in acral lentiginous melanomas…..…82
Table 16. Patient clinicopathological data………………………………...……………84
Table 17. Factors associated with the stress- and non-stress-bearing areas……………86
Table 18. Univariate and multivariate analyses results of risk factors associated with overall survival……………............................................................................................87
Table 19. Univariate and multivariate analyses results of risk factors associated with distant metastasis-free survival……………....................................................................88
Table 20. Univariate and multivariate analyses results of risk factors associated with recurrence-free survival……………...............................................................................89
附錄:已發表之論文 (Publication list)………………………………………….…….90
1.Wu CE, Hsieh CH, Chang CJ, Yeh JT, Kuo TT, Yang CH, et al. Prognostic factors for Taiwanese patients with cutaneous melanoma undergoing sentinel lymph node biopsy. J Formos Med Assoc. 2015;114:415-21. doi: 10.1016/j.jfma.2013.06.018 PMID: 23969039
2.Kim SY, Yun SJ. Cutaneous melanoma in Asians. Chonnam Med J. 2016;52:185-93. doi: 10.4068/cmj.2016.52.3.185 PMID: 27689028
3.Chen YJ, Wu CY, Chen JT, Shen JL, Chen CC, Wang HC. Clinicopathologic analysis of malignant melanoma in Taiwan. J Am Acad Dermatol. 1999;41:945-9. PMID: 10570378
4.Chang JW. Cutaneous melanoma: Taiwan experience and literature review. Chang Gung Med J. 2010;33:602-12. PMID: 21199605
5.Wu CE, Hsieh CH, Chang CJ, Yeh JT, Kuo TT, Yang CH, et al. Prognostic factors for Taiwanese patients with cutaneous melanoma undergoing sentinel lymph node biopsy. J Formos Med Assoc. 2013. doi: 10.1016/j.jfma.2013.06.018 PMID: 23969039
6.Soong CY, Liu HN, Ger LP, Chu TL, Syu HL, Tseng HH. Malignant melanoma: a clinicopathologic study of 22 cases. J Formos Med Assoc. 1991;90:365-70. PMID: 1680965
7.Jung HJ, Kweon SS, Lee JB, Lee SC, Yun SJ. A clinicopathologic analysis of 177 acral melanomas in Koreans: relevance of spreading pattern and physical stress. JAMA Dermatol. 2013;149:1281-8. doi: 10.1001/jamadermatol.2013.5853 PMID: 24067997
8.Soon SL, Solomon AR, Jr., Papadopoulos D, Murray DR, McAlpine B, Washington CV. Acral lentiginous melanoma mimicking benign disease: the Emory experience. J Am Acad Dermatol. 2003;48:183-8. doi: 10.1067/mjd.2003.63 PMID: 12582386
9.Choi YD, Chun SM, Jin SA, Lee JB, Yun SJ. Amelanotic acral melanomas: clinicopathological, BRAF mutation, and KIT aberration analyses. J Am Acad Dermatol. 2013;69:700-7. doi: 10.1016/j.jaad.2013.06.035 PMID: 23972510
10.Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med. 2015;373:1926-36. doi: 10.1056/NEJMoa1502583 PMID: 26559571
11.Lee JH, Choi JW, Kim YS. Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis. Br J Dermatol. 2011;164:776-84. doi: 10.1111/j.1365-2133.2010.10185.x PMID: 21166657
12.Zebary A, Omholt K, Vassilaki I, Hoiom V, Linden D, Viberg L, et al. KIT, NRAS, BRAF and PTEN mutations in a sample of Swedish patients with acral lentiginous melanoma. J Dermatol Sci. 2013;72:284-9. doi: 10.1016/j.jdermsci.2013.07.013 PMID: 23993026
13.Kong Y, Si L, Zhu Y, Xu X, Corless CL, Flaherty KT, et al. Large-scale analysis of KIT aberrations in Chinese patients with melanoma. Clin Cancer Res. 2011;17:1684-91. doi: 10.1158/1078-0432.CCR-10-2346 PMID: 21325067
14.Ashida A, Takata M, Murata H, Kido K, Saida T. Pathological activation of KIT in metastatic tumors of acral and mucosal melanomas. Int J Cancer. 2009;124:862-8. doi: 10.1002/ijc.24048 PMID: 19035443
15.Yun J, Lee J, Jang J, Lee EJ, Jang KT, Kim JH, et al. KIT amplification and gene mutations in acral/mucosal melanoma in Korea. APMIS. 2011;119:330-5. doi: 10.1111/j.1600-0463.2011.02737.x PMID: 21569090
16.Green A, McCredie M, MacKie R, Giles G, Young P, Morton C, et al. A case-control study of melanomas of the soles and palms (Australia and Scotland). Cancer Causes Control. 1999;10:21-5. PMID: 10334638
17.Minagawa A, Omodaka T, Okuyama R. Melanomas and mechanical stress points on the plantar surface of the foot. N Engl J Med. 2016;374:2404-6. doi: 10.1056/NEJMc1512354 PMID: 27305207
18.Shen YC, W.C. C, Hsieh JJ, H.Y. C, Hou MM, Hisieh CH, et al. Incidence of BRAF and C-KIT mutations in Taiwanese melanoma. Proceedings from the XXII International Pigment Cell Conference. 2014.
19.Sheen YS, Liao YH, Liau JY, Lin MH, Hsieh YC, Jee SH, et al. Prevalence of BRAF and NRAS mutations in cutaneous melanoma patients in Taiwan. J Formos Med Assoc. 2015. doi: 10.1016/j.jfma.2015.02.001 PMID: 25767048
20.Liao B, Hu Y, Herrick DJ, Brewer G. The RNA-binding protein IMP-3 is a translational activator of insulin-like growth factor II leader-3 mRNA during proliferation of human K562 leukemia cells. J Biol Chem. 2005;280:18517-24. doi: 10.1074/jbc.M500270200 PMID: 15753088
21.Mueller-Pillasch F, Lacher U, Wallrapp C, Micha A, Zimmerhackl F, Hameister H, et al. Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene. 1997;14:2729-33. doi: 10.1038/sj.onc.1201110 PMID: 9178771
22.Jeng YM, Chang CC, Hu FC, Chou HY, Kao HL, Wang TH, et al. RNA-binding protein insulin-like growth factor II mRNA-binding protein 3 expression promotes tumor invasion and predicts early recurrence and poor prognosis in hepatocellular carcinoma. Hepatology. 2008;48:1118-27. doi: 10.1002/hep.22459 PMID: 18802962
23.Pryor JG, Bourne PA, Yang Q, Spaulding BO, Scott GA, Xu H. IMP-3 is a novel progression marker in malignant melanoma. Mod Pathol. 2008;21:431-7. doi: 10.1038/modpathol.3801016 PMID: 18204432
24.Yu L, Xu H, Wasco MJ, Bourne PA, Ma L. IMP-3 expression in melanocytic lesions. J Cutan Pathol. 2010;37:316-22. doi: 10.1111/j.1600-0560.2009.01428.x PMID: 19788446
25.Jiang Z, Chu PG, Woda BA, Rock KL, Liu Q, Hsieh CC, et al. Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study. Lancet Oncol. 2006;7:556-64. doi: 10.1016/S1470-2045(06)70732-X PMID: 16814207
26.Yuan RH, Wang CC, Chou CC, Chang KJ, Lee PH, Jeng YM. Diffuse expression of RNA-binding protein IMP3 predicts high-stage lymph node metastasis and poor prognosis in colorectal adenocarcinoma. Ann Surg Oncol. 2009;16:1711-9. doi: 10.1245/s10434-009-0446-0 PMID: 19357927
27.Sheen YS, Liao YH, Lin MH, Chu CY, Ho BY, Hsieh MC, et al. IMP-3 promotes migration and invasion of melanoma cells by modulating the expression of HMGA2 and predicts poor prognosis in melanoma. J Invest Dermatol. 2015;135:1065-73. doi: 10.1038/jid.2014.480 PMID: 25380351
28.Kabbarah O, Nogueira C, Feng B, Nazarian RM, Bosenberg M, Wu M, et al. Integrative genome comparison of primary and metastatic melanomas. PLoS One. 2010;5:e10770. doi: 10.1371/journal.pone.0010770 PMID: 20520718
29.Sheen YS, Liao YH, Lin MH, Chiu HC, Jee SH, Liau JY, et al. Insulin-like growth factor II mRNA-binding protein 3 expression correlates with poor prognosis in acral lentiginous melanoma. PLoS One. 2016;11:e0147431. doi: 10.1371/journal.pone.0147431 PMID: 26796627
30.Raskin L, Fullen DR, Giordano TJ, Thomas DG, Frohm ML, Cha KB, et al. Transcriptome profiling identifies HMGA2 as a biomarker of melanoma progression and prognosis. J Invest Dermatol. 2013;133:2585-92. doi: 10.1038/jid.2013.197 PMID: 23633021
31.Jin SA, Chun SM, Choi YD, Kweon SS, Jung ST, Shim HJ, et al. BRAF mutations and KIT aberrations and their clinicopathological correlation in 202 Korean melanomas. J Invest Dermatol. 2013;133:579-82. doi: 10.1038/jid.2012.338 PMID: 23014346
32.Ackerman AB. What naevus is dysplastic, a syndrome and the commonest precursor of malignant melanoma? A riddle and an answer. Histopathology. 1988;13:241-56. PMID: 3056824
33.Togawa Y, Nakamura Y, Kamada N, Kambe N, Takahashi Y, Matsue H. Melanoma in association with acquired melanocytic nevus in Japan: a review of cases in the literature. Int J Dermatol. 2010;49:1362-7. PMID: 21155082
34.Al-Jamal MS, Griffith JL, Lim HW. Photoprotection in ethnic skin. Dermatologica Sinica. 2014;32:217-24. doi: 10.1016/j.dsi.2014.09.001
35.Sheen YS, Liao YH, Lin MH, Chen JS, Liau JY, Liang CW, et al. Clinicopathological features and prognosis of patients with de novo versus nevus-associated melanoma in Taiwan. PLoS One. 2017;12:e0177126. doi: 10.1371/journal.pone.0177126 PMID: 28472158
36.Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199-206. doi: 10.1200/JCO.2009.23.4799 PMID: 19917835
37.Lin WM, Luo S, Muzikansky A, Lobo AZ, Tanabe KK, Sober AJ, et al. Outcome of patients with de novo versus nevus-associated melanoma. J Am Acad Dermatol. 2015;72:54-8. doi: 10.1016/j.jaad.2014.09.028 PMID: 25440436
38.Friedman RJ, Rigel DS, Kopf AW, Lieblich L, Lew R, Harris MN, et al. Favorable prognosis for malignant melanomas associated with acquired melanocytic nevi. Arch Dermatol. 1983;119:455-62. PMID: 6859885
39.Kaddu S, Smolle J, Zenahlik P, Hofmann-Wellenhof R, Kerl H. Melanoma with benign melanocytic naevus components: reappraisal of clinicopathological features and prognosis. Melanoma Res. 2002;12:271-8. PMID: 12140384
40.Dwyer PK, Mackie RM, Watt DC, Aitchison TC. Plantar malignant melanoma in a white Caucasian population. Br J Dermatol. 1993;128:115-20. PMID: 8457443
41.Sheen YS, Liao YH, Lin MH, Chen JS, Liau JY, Tseng YJ, et al. A clinicopathological analysis of 153 acral melanomas and the relevance of mechanical stress. Sci Rep. 2017;7:5564. doi: 10.1038/s41598-017-05809-9 PMID: 28717212
42.Mervic L. Prognostic factors in patients with localized primary cutaneous melanoma. Acta Dermatovenerol Alp Pannonica Adriat. 2012;21:27-31. PMID: 23000937
43.Betti R, Santambrogio R, Cerri A, Vergani R, Moneghini L, Menni S. Observational study on the mitotic rate and other prognostic factors in cutaneous primary melanoma arising from naevi and from melanoma de novo. J Eur Acad Dermatol Venereol. 2014;28:1738-41. doi: 10.1111/jdv.12395 PMID: 24673663
44.Shitara D, Nascimento MM, Puig S, Yamada S, Enokihara MM, Michalany N, et al. Nevus-associated melanomas: clinicopathologic features. Am J Clin Pathol. 2014;142:485-91. doi: 10.1309/AJCP4L5CJGKTJVDD PMID: 25239415
45.Jeng YM, Wang TH, Lu SH, Yuan RH, Hsu HC. Prognostic significance of insulin-like growth factor II mRNA-binding protein 3 expression in gastric adenocarcinoma. Br J Surg. 2009;96:66-73. doi: 10.1002/bjs.6438 PMID: 19109797
46.Chokoeva AA, Ananiev J, Wollina U, Tana C, Lotti T, Cardoso JC, et al. Imp-3 Expression in Benign Melanocytic Nevi, Dysplastic Nevi and Malignant Melanoma: Preliminary Findings in Bulgarian Patients. J Biol Regul Homeost Agents. 2015;29:695-9. PMID: 26403409
47.Brozyna AA, Jozwicki W, Carlson JA, Slominski AT. Melanogenesis affects overall and disease-free survival in patients with stage III and IV melanoma. Hum Pathol. 2013;44:2071-4. doi: 10.1016/j.humpath.2013.02.022 PMID: 23791398
48.Chraybi M, Abd Alsamad I, Copie-Bergman C, Baia M, Andre J, Dumaz N, et al. Oncogene abnormalities in a series of primary melanomas of the sinonasal tract: NRAS mutations and cyclin D1 amplification are more frequent than KIT or BRAF mutations. Hum Pathol. 2013;44:1902-11. doi: 10.1016/j.humpath.2013.01.025 PMID: 23664541
49.Chi Z, Li S, Sheng X, Si L, Cui C, Han M, et al. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases. BMC Cancer. 2011;11:85. doi: 10.1186/1471-2407-11-85 PMID: 21349197
50.Gao TW, Sun DJ, Li CY, He H, Li Q, Liu YS, et al. [Retrospective analysis of 1905 patients with skin cancer from two general hospitals in western China from 1981 to 2000]. Beijing Da Xue Xue Bao. 2004;36:469-72. PMID: 15489924
51.Uhara H, Ashida A, Koga H, Ogawa E, Uchiyama A, Uchiyama R, et al. NRAS mutations in primary and metastatic melanomas of Japanese patients. Int J Clin Oncol. 2014;19:544-8. doi: 10.1007/s10147-013-0573-2 PMID: 23739925
52.Si L, Kong Y, Xu X, Flaherty KT, Sheng X, Cui C, et al. Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort. Eur J Cancer. 2012;48:94-100. doi: 10.1016/j.ejca.2011.06.056 PMID: 21788131
53.Ellerhorst JA, Greene VR, Ekmekcioglu S, Warneke CL, Johnson MM, Cooke CP, et al. Clinical correlates of NRAS and BRAF mutations in primary human melanoma. Clin Cancer Res. 2011;17:229-35. doi: 10.1158/1078-0432.CCR-10-2276 PMID: 20975100
54.Lee HY, Chay WY, Tang MB, Chio MT, Tan SH. Melanoma: differences between Asian and Caucasian patients. Ann Acad Med Singapore. 2012;41:17-20. PMID: 22499476
55.Garbe C, McLeod GR, Buettner PG. Time trends of cutaneous melanoma in Queensland, Australia and Central Europe. Cancer. 2000;89:1269-78. PMID: 11002222
56.Youl PH, Youlden DR, Baade PD. Changes in the site distribution of common melanoma subtypes in Queensland, Australia over time: implications for public health campaigns. Br J Dermatol. 2013;168:136-44. doi: 10.1111/j.1365-2133.2012.11064.x PMID: 22612718
57.Mayer JE, Swetter SM, Fu T, Geller AC. Screening, early detection, education, and trends for melanoma: current status (2007-2013) and future directions: Part II. Screening, education, and future directions. J Am Acad Dermatol. 2014;71:611 e1- e10; quiz 21-2. doi: 10.1016/j.jaad.2014.05.045 PMID: 25219717
58.Geller AC, Clapp RW, Sober AJ, Gonsalves L, Mueller L, Christiansen CL, et al. Melanoma epidemic: an analysis of six decades of data from the Connecticut Tumor Registry. J Clin Oncol. 2013;31:4172-8. doi: 10.1200/JCO.2012.47.3728 PMID: 24043747
59.Tanaka H, Tsukuma H, Tomita S, Ajiki W, Kitagawa T, Kinoshita N, et al. Time trends of incidence for cutaneous melanoma among the Japanese population: an analysis of Osaka Cancer Registry data, 1964-95. J Epidemiol. 1999;9:S129-35. PMID: 10709361
60.Sng J, Koh D, Siong WC, Choo TB. Skin cancer trends among Asians living in Singapore from 1968 to 2006. J Am Acad Dermatol. 2009;61:426-32. doi: 10.1016/j.jaad.2009.03.031 PMID: 19628302
61.Reintgen DS, McCarty KM, Jr., Cox E, Seigler HF. Malignant melanoma in black American and white American populations. A comparative review. JAMA. 1982;248:1856-9. PMID: 7120604
62.Luk NM, Ho LC, Choi CL, Wong KH, Yu KH, Yeung WK. Clinicopathological features and prognostic factors of cutaneous melanoma among Hong Kong Chinese. Clin Exp Dermatol. 2004;29:600-4. doi: 10.1111/j.1365-2230.2004.01644.x PMID: 15550131
63.Yamazaki N, Tanaka R, Tsutsumida A, Namikawa K, Eguchi H, Omata W, et al. BRAF V600 mutations and pathological features in Japanese melanoma patients. Melanoma Res. 2015;25:9-14. doi: 10.1097/CMR.0000000000000091 PMID: 25051202
64.Krementz ET, Feed RJ, Coleman WP, 3rd, Sutherland CM, Carter RD, Campbell M. Acral lentiginous melanoma. A clinicopathologic entity. Ann Surg. 1982;195:632-45. PMID: 7073361
65.Slingluff CL, Jr., Vollmer R, Seigler HF. Acral melanoma: a review of 185 patients with identification of prognostic variables. J Surg Oncol. 1990;45:91-8. PMID: 2214797
66.Ashida A, Uhara H, Kiniwa Y, Oguchi M, Murata H, Goto Y, et al. Assessment of BRAF and KIT mutations in Japanese melanoma patients. J Dermatol Sci. 2012;66:240-2. doi: 10.1016/j.jdermsci.2012.03.005 PMID: 22534474
67.Zhou QM, Li W, Zhang X, Chen YB, Chen XC, Guan YX, et al. The mutation profiles of common oncogenes involved in melanoma in southern China. J Invest Dermatol. 2012;132:1935-7. doi: 10.1038/jid.2012.64 PMID: 22437319
68.Qi RQ, He L, Zheng S, Hong Y, Ma L, Zhang S, et al. BRAF exon 15 T1799A mutation is common in melanocytic nevi, but less prevalent in cutaneous malignant melanoma, in Chinese Han. J Invest Dermatol. 2011;131:1129-38. doi: 10.1038/jid.2010.405 PMID: 21326296
69.Sasaki Y, Niu C, Makino R, Kudo C, Sun C, Watanabe H, et al. BRAF point mutations in primary melanoma show different prevalences by subtype. J Invest Dermatol. 2004;123:177-83. doi: 10.1111/j.0022-202X.2004.22722.x PMID: 15191558
70.Hong JW, Lee S, Kim DC, Kim KH, Song KH. Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral Lentiginous Melanoma in Korean Patients: A Preliminary Study. Ann Dermatol. 2014;26:195-202. doi: 10.5021/ad.2014.26.2.195 PMID: 24882974
71.Giehl K. Oncogenic Ras in tumour progression and metastasis. Biol Chem. 2005;386:193-205. doi: 10.1515/BC.2005.025 PMID: 15843165
72.Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135-47. doi: 10.1056/NEJMoa050092 PMID: 16291983
73.Bauer J, Buttner P, Murali R, Okamoto I, Kolaitis NA, Landi MT, et al. BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site. Pigment Cell Melanoma Res. 2011;24:345-51. doi: 10.1111/j.1755-148X.2011.00837.x PMID: 21324100
74.Liu W, Kelly JW, Trivett M, Murray WK, Dowling JP, Wolfe R, et al. Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol. 2007;127:900-5. doi: 10.1038/sj.jid.5700632 PMID: 17159915
75.Durbec F, Martin L, Derancourt C, Grange F. Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review. Br J Dermatol. 2012;166:727-39. doi: 10.1111/j.1365-2133.2011.10772.x PMID: 22175696
76.Fedorenko IV, Gibney GT, Smalley KS. NRAS mutant melanoma: biological behavior and future strategies for therapeutic management. Oncogene. 2013;32:3009-18. doi: 10.1038/onc.2012.453 PMID: 23069660
77.Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124:619-26. PMID: 8106557
78.Owen SA, Sanders LL, Edwards LJ, Seigler HF, Tyler DS, Grichnik JM. Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV. Cancer. 2001;91:983-91. PMID: 11251950
79.Egger ME, McMasters KM, Callender GG, Quillo AR, Martin RC, 2nd, Stromberg AJ, et al. Unique prognostic factors in acral lentiginous melanoma. Am J Surg. 2012;204:874-9; discussion 9-80. doi: 10.1016/j.amjsurg.2012.05.013 PMID: 23022254
80.Jonson L, Christiansen J, Hansen TV, Vikesa J, Yamamoto Y, Nielsen FC. IMP3 RNP safe houses prevent miRNA-directed HMGA2 mRNA decay in cancer and development. Cell Rep. 2014;7:539-51. doi: 10.1016/j.celrep.2014.03.015 PMID: 24703842
81.Brozyna AA, VanMiddlesworth L, Slominski AT. Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy. Int J Cancer. 2008;123:1448-56. doi: 10.1002/ijc.23664 PMID: 18567001
82.Slominski A, Kim TK, Brozyna AA, Janjetovic Z, Brooks DL, Schwab LP, et al. The role of melanogenesis in regulation of melanoma behavior: melanogenesis leads to stimulation of HIF-1alpha expression and HIF-dependent attendant pathways. Arch Biochem Biophys. 2014;563:79-93. doi: 10.1016/j.abb.2014.06.030 PMID: 24997364
83.Slominski A, Zbytek B, Slominski R. Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells. Int J Cancer. 2009;124:1470-7. doi: 10.1002/ijc.24005 PMID: 19085934
84.Lv J, Dai B, Kong Y, Shen X, Kong J. Acral melanoma in Chinese: a clinicopathological and prognostic study of 142 cases. Sci Rep. 2016;6:31432. doi: 10.1038/srep31432 PMID: 27545198
85.Cymerman RM, Shao Y, Wang K, Zhang Y, Murzaku EC, Penn LA, et al. De novo vs nevus-associated melanomas: differences in associations with prognostic indicators and survival. J Natl Cancer Inst. 2016;108. doi: 10.1093/jnci/djw121 PMID: 27235387
86.Tzen CY, Wu YH, Tzen CY. Characterization of KIT mutation in melanoma. Dermatol Sin. 2014;32:7-12.
87.Smoller BR. Histologic criteria for diagnosing primary cutaneous malignant melanoma. Mod Pathol. 2006;19 Suppl 2:S34-40. doi: 10.1038/modpathol.3800508 PMID: 16446714
88.Haenssle HA, Mograby N, Ngassa A, Buhl T, Emmert S, Schon MP, et al. Association of patient risk factors and frequency of nevus-associated cutaneous melanomas. JAMA Dermatol. 2015:1-8. doi: 10.1001/jamadermatol.2015.3775 PMID: 26536613
89.Fernandez LP, Milne RL, Pita G, Floristan U, Sendagorta E, Feito M, et al. Pigmentation-related genes and their implication in malignant melanoma susceptibility. Exp Dermatol. 2009;18:634-42. doi: 10.1111/j.1600-0625.2009.00846.x PMID: 19320733
90.Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous melanomas associated with nevi. Arch Dermatol. 2003;139:1620-4; discussion 4. doi: 10.1001/archderm.139.12.1620 PMID: 14676081
91.Rhodes AR, Harrist TJ, Day CL, Mihm MC, Jr., Fitzpatrick TB, Sober AJ. Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas. J Am Acad Dermatol. 1983;9:563-74. PMID: 6630618
92.Weatherhead SC, Haniffa M, Lawrence CM. Melanomas arising from naevi and de novo melanomas--does origin matter? Br J Dermatol. 2007;156:72-6. doi: 10.1111/j.1365-2133.2006.07570.x PMID: 17199569
93.Harley S, Walsh N. A new look at nevus-associated melanomas. Am J Dermatopathol. 1996;18:137-41. PMID: 8739987
94.Baer SC, Schultz D, Synnestvedt M, Elder DE. Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma. Cancer. 1995;76:2242-7. PMID: 8635027
95.Cormier JN, Xing Y, Ding M, Lee JE, Mansfield PF, Gershenwald JE, et al. Ethnic differences among patients with cutaneous melanoma. Arch Intern Med. 2006;166:1907-14. doi: 10.1001/archinte.166.17.1907 PMID: 17000949
96.Duman N, Erkin G, Gokoz O, Karahan S, Kayikcioglu AU, Celik I. Nevus-Associated versus de novo Melanoma: Do They Have Different Characteristics and Prognoses? Dermatopathology (Basel). 2015;2:46-51. doi: 10.1159/000375490 PMID: 27047934
97.Phan A, Touzet S, Dalle S, Ronger-Savle S, Balme B, Thomas L. Acral lentiginous melanoma: a clinicoprognostic study of 126 cases. Br J Dermatol. 2006;155:561-9. doi: 10.1111/j.1365-2133.2006.07368.x PMID: 16911282
98.Saida T. Morphological and molecular uniqueness of acral melanoma. Expert Review of Dermatology. 2014;2:125-31. doi: 10.1586/17469872.2.2.125
99.Minagawa A, Omodaka T, Koga H, Yokokawa Y, Uhara H, Okuyama R. Nail apparatus melanoma thickness is associated with side and age. Br J Dermatol. 2017. doi: 10.1111/bjd.15318 PMID: 28117487
100.Liu L, Zhang W, Gao T, Li C. Is UV an etiological factor of acral melanoma? J Expo Sci Environ Epidemiol. 2016;26:539-45. doi: 10.1038/jes.2015.60 PMID: 26464096
101.Ishihara K, Saida T, Yamamoto A, Japanese Skin Cancer Society P, Statistical Investigation C. Updated statistical data for malignant melanoma in Japan. Int J Clin Oncol. 2001;6:109-16. PMID: 11706778
102.Stucke S, McFarland D, Goss L, Fonov S, McMillan GR, Tucker A, et al. Spatial relationships between shearing stresses and pressure on the plantar skin surface during gait. J Biomech. 2012;45:619-22. doi: 10.1016/j.jbiomech.2011.11.004 PMID: 22169152
103.Bristow I, Bower C. Melanoma of the foot. Clin Podiatr Med Surg. 2016;33:409-22. doi: 10.1016/j.cpm.2016.02.008 PMID: 27215160
104.Hosokawa M, Kato T, Seiji M, Abe R. Plantar malignant melanoma. Statistical and clinicopathological studies. J Dermatol. 1980;7:137-42. PMID: 6991569
105.Rehim SA, Kowalski E, Chung KC. Enhancing aesthetic outcomes of soft-tissue coverage of the hand. Plast Reconstr Surg. 2015;135:413e-28e. doi: 10.1097/PRS.0000000000001069 PMID: 25626826
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