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结膜鳞状细胞癌中 EGFR 的表达、细胞内定位、突变及其与预后和治疗的关系。

Expression, intracellular localization, and mutation of EGFR in conjunctival squamous cell carcinoma and the association with prognosis and treatment.

机构信息

Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Ophthalmology Department and Eye Center, Kobe Kaisei Hospital, Kobe, Hyogo, Japan.

出版信息

PLoS One. 2020 Aug 24;15(8):e0238120. doi: 10.1371/journal.pone.0238120. eCollection 2020.

Abstract

PURPOSE

Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC.

METHODS

In this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs.

RESULTS

All 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival.

CONCLUSIONS

EGFR is important in the pathology of ocular surface squamous neoplasia including SCC and is a prognostic factor. Increased understanding of EGFR mutations may have important implications for future treatment options.

摘要

目的

结膜鳞状细胞癌(SCC)主要通过手术切除进行治疗。SCC 有不同的阶段,局部复发很常见。本研究的目的是确定表皮生长因子受体(EGFR)的分子定位以及 EGFR 作为结膜 SCC 管理生物标志物的可能性。

方法

在这项回顾性研究中,我们进行了免疫组织化学分析,以评估肿瘤细胞中 EGFR 的表达和定位、EGFR 突变特异性表达(E746-A750del 和 L858R)以及人乳头瘤病毒在一系列 29 例结膜 SCC 中的表达。

结果

我们队列中的所有 29 个肿瘤均为 EGFR 阳性(100%)。29 个肿瘤中的 21 个(72%)显示局灶性 EGFR 染色,7 个(28%)显示弥漫性 EGFR 染色。此外,我们计算了 EGFR 中两个最重要的突变(外显子 19 746-A750del(29 例中的 8 例,27.5%)和外显子 21(L858R 突变体(29 例中的 2 例,6.8%)在结膜 SCC 中的百分比。我们观察到 EGFR 从膜转移到细胞质与临床预后相关,因为我们检测到 EGFR 细胞质染色与最终眼眶切除术之间以及 EGFR 膜染色减少与无进展生存期之间存在相关性。

结论

EGFR 在包括 SCC 在内的眼表鳞状上皮肿瘤的病理学中很重要,是一个预后因素。对 EGFR 突变的深入了解可能对未来的治疗选择具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ac4/7444806/894bf0347b41/pone.0238120.g001.jpg

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