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隆突性皮肤纤维肉瘤:临床病理特征及相关 Akt/mTOR、STAT3、ERK、cyclin D1 和 PD-L1 表达的回顾性研究。

Dermatofibrosarcoma protuberans: A retrospective study of clinicopathologic features and related Akt/mTOR, STAT3, ERK, cyclin D1, and PD-L1 expression.

机构信息

Department of Pathology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Department of Dermatology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

J Am Acad Dermatol. 2018 Nov;79(5):843-852. doi: 10.1016/j.jaad.2018.05.016. Epub 2018 May 22.

Abstract

BACKGROUND

Little is known regarding oncoproteins other than platelet-derived growth factor subunit B in dermatofibrosarcoma protuberans (DFSP). Moreover, the risk factors for worse prognosis are controversial.

OBJECTIVE

We sought to determine the clinicopathologic features and key factors for adverse outcome in DFSP, including the implication of expression of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), extracellular signal regulated kinase (ERK), cyclin D1, and programmed death ligand 1 (PD-L1).

METHODS

Clinicopathologic and immunohistochemical analyses were performed for 44 DFSPs having wide local excision and 92 dermatofibromas as controls.

RESULTS

Compared with the 35 nonrecurrent DFSPs, the 9 recurrent DFSPs exhibited larger tumor size, deeper invasion beyond the subcutis, and more diverse histologic subtype. The fibrosarcomatous subtype revealed frequent mitotic figures and a high cyclin D1-positive index. The 2 metastatic DFSPs (1 each of the fibrosarcomatous and myxoid subtypes) demonstrated 4 and 11 instances of local recurrence, respectively, as well as larger tumor size, deeper invasion beyond the subcutis, and high expression of cyclin D1. Expression of Akt/mTOR, STAT3, ERK, and PD-L1 ranged from none or low in the primary skin lesions to high in the corresponding metastatic sites. Akt/mTOR and ERK were expressed more frequently in DFSP than in dermatofibroma.

LIMITATIONS

Lack of information on patients before hospital evaluation.

CONCLUSION

Complex factors beyond fibrosarcomatous subtype may portend local recurrence or metastasis. Akt/mTOR, STAT3, ERK, and PD-L1 may be associated with development and/or progression of DFSP.

摘要

背景

除了隆突性皮肤纤维肉瘤(DFSP)中的血小板衍生生长因子亚单位 B 以外,人们对其他癌蛋白知之甚少。此外,预后不良的危险因素存在争议。

目的

我们旨在确定 DFSP 的临床病理特征和不良预后的关键因素,包括蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)、信号转导和转录激活因子 3(STAT3)、细胞外信号调节激酶(ERK)、细胞周期蛋白 D1 和程序性死亡配体 1(PD-L1)表达的意义。

方法

对行广泛局部切除的 44 例 DFSP 和 92 例皮肤纤维瘤进行临床病理和免疫组织化学分析。

结果

与 35 例非复发性 DFSP 相比,9 例复发性 DFSP 的肿瘤较大,超出皮下组织的浸润更深,组织学亚型更多样。纤维肉瘤型表现为频繁的有丝分裂和较高的细胞周期蛋白 D1 阳性指数。2 例(纤维肉瘤型和黏液样型各 1 例)转移性 DFSP 分别发生了 4 次和 11 次局部复发,且肿瘤较大,超出皮下组织的浸润更深,细胞周期蛋白 D1 表达较高。Akt/mTOR、STAT3、ERK 和 PD-L1 的表达从原发皮肤病变的无或低表达到相应转移部位的高表达。Akt/mTOR 和 ERK 在 DFSP 中的表达比在皮肤纤维瘤中更为频繁。

局限性

缺乏患者在医院评估前的信息。

结论

除纤维肉瘤型以外的复杂因素可能预示着局部复发或转移。Akt/mTOR、STAT3、ERK 和 PD-L1 可能与 DFSP 的发生和/或进展有关。

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