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Adipophilin expression in cutaneous malignant melanoma is associated with high proliferation and poor clinical prognosis.
Laboratory Investigation ( IF 5 ) Pub Date : 2019-12-19 , DOI: 10.1038/s41374-019-0358-y
Masakazu Fujimoto 1 , Ibu Matsuzaki 1 , Kazuchika Nishitsuji 2 , Yuki Yamamoto 3 , Daisuke Murakami 4 , Takanori Yoshikawa 5 , Ayaka Fukui 1 , Yuuki Mori 1 , Masaru Nishino 1 , Yuichi Takahashi 1 , Yoshifumi Iwahashi 1 , Kenji Warigaya 1 , Fumiyoshi Kojima 1 , Masatoshi Jinnin 3 , Shin-Ichi Murata 1
Affiliation  

Adipophilin (ADP) is a primary protein component of lipid droplets (LDs). For more than half a century, certain types of cancer cells have been known to contain LDs in their cytoplasm. However, the pathological significance of ADP or LDs in cancer remains unclear. In the present study, we investigated the association between ADP and other pathological characteristics in cutaneous malignant melanomas to clarify the role of ADP in melanoma cells. We immunostained whole paraffin sections of primary cutaneous melanomas obtained from 90 cases for ADP, after which we analyzed the correlation between ADP immunohistochemistry (IHC) and patient survival data. We also studied the relationship between the ADP IHC score and in situ hybridization (ISH) score of ADP mRNA, and the Ki67-labeling index (Ki67-LI) by using tissue microarrays consisting of 74 primary cutaneous malignant melanomas, 19 metastasizing melanomas, and 29 melanocytic nevi. Finally, we analyzed the relationship between ADP expression and cell proliferation in cutaneous melanoma cell lines. We found that high ADP expression was associated with poor metastasis-free survival, disease-specific survival, and overall survival rates of patients with cutaneous melanomas (P < 0.05). By linear regression analysis, ADP IHC was correlated with increasing ADP mRNA ISH H-scores and Ki67-LI scores in melanocytic lesions (P < 0.01). ADP IHC and ADP ISH H-scores and Ki67-LI scores were greater in pT3-4 melanomas than in pT1-2 melanomas. In cell-based assays, cells with increased ADP expression showed higher proliferation rates compared with those of low-ADP cells. Thus, ADP expression in malignant melanoma was significantly associated with high cell proliferation and poor clinical prognosis. Our results thus indicate a significant association between ADP and melanoma progression, and we propose that ADP may be a novel marker of aggressive cutaneous melanoma with a lipogenic phenotype.

中文翻译:

皮肤恶性黑色素瘤中的 Adipophilin 表达与高增殖和不良临床预后相关。

Adipophilin (ADP) 是脂滴 (LD) 的主要蛋白质成分。半个多世纪以来,已知某些类型的癌细胞在其细胞质中含有 LD。然而,ADP 或 LDs 在癌症中的病理学意义仍不清楚。在本研究中,我们研究了 ADP 与皮肤恶性黑色素瘤其他病理特征之间的关联,以阐明 ADP 在黑色素瘤细胞中的作用。我们对 90 例原发性皮肤黑色素瘤的整个石蜡切片进行 ADP 免疫染色,之后我们分析了 ADP 免疫组织化学 (IHC) 与患者生存数据之间的相关性。我们还研究了 ADP IHC 评分与 ADP mRNA 原位杂交 (ISH) 评分之间的关​​系,和 Ki67 标记指数 (Ki67-LI),使用由 74 个原发性皮肤恶性黑色素瘤、19 个转移性黑色素瘤和 29 个黑色素细胞痣组成的组织微阵列。最后,我们分析了皮肤黑色素瘤细胞系中 ADP 表达与细胞增殖之间的关系。我们发现,ADP 高表达与皮肤黑色素瘤患者的无转移生存率、疾病特异性生存率和总生存率差相关 (P < 0.05)。通过线性回归分析,ADP IHC 与黑色素细胞病变中增加的 ADP mRNA ISH H 评分和 Ki67-LI 评分相关(P < 0.01)。pT3-4 黑色素瘤的 ADP IHC 和 ADP ISH H 评分和 Ki67-LI 评分高于 pT1-2 黑色素瘤。在基于细胞的测定中,与低ADP细胞相比,ADP表达增加的细胞显示出更高的增殖率。因此,恶性黑色素瘤中的 ADP 表达与高细胞增殖和不良临床预后显着相关。因此,我们的结果表明 ADP 与黑色素瘤进展之间存在显着关联,我们提出 ADP 可能是具有脂肪生成表型的侵袭性皮肤黑色素瘤的新标志物。
更新日期:2019-12-20
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