Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Osaka City University, 1-5-7 Asahimachi, Abeno-ku, Osaka-shi, Osaka, 545-8585, Japan.
Ophthalmology Department and Eye Center, Kobe Kaisei Hospital, Kobe, Hyogo, Japan.
Graefes Arch Clin Exp Ophthalmol. 2021 Oct;259(10):3127-3136. doi: 10.1007/s00417-021-05236-7. Epub 2021 May 29.
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 investigate thrombospondin-1 expression and its association with prognosis.
In this retrospective study, a gene expression array along with immunohistochemistry were performed for the evaluation of thrombospondin-1 expression, localization, as well as Ki67 labeling cell indices in carcinoma in situ (Tis) and advanced conjunctival SCC (Tadv). The presence or absence and intensity of cytoplasmic and nuclear staining in tumor cells were also divided into groups with a score of 0-3 and semi-quantitatively analyzed to investigate intracellular staining patterns. The association between thrombospondin-1 expression and tumor progression in a series of 31 conjunctival SCCs was further investigated.
All 31 patients in the cohort (100%) were East Asian. A simple comparison between Tis and Tadv demonstrated significant differences in expressions of 45 genes, including thrombospondin-1 (p < 0.01). In this cohort, 30/31 tumors were positive (96%) for thrombospondin-1. Furthermore, thrombospondin-1 intracellular staining pattern analysis scores were 2.12 and 0.96 for nuclear and cytoplasmic staining, respectively, with a significant difference observed between Tis and Tadv (p < 0.01). Alteration of the Ki67 labeling index was significantly correlated with that of the thrombospondin-1 cytoplasmic score (p = 0.030). Furthermore, univariate Cox regression analysis showed a significant correlation between thrombospondin-1 staining and progression-free survival (p = 0.026) and final orbital exenteration (p = 0.019).
The present results demonstrated that thrombospondin-1 is a potential molecular target in the pathology of conjunctival SCC, in addition to serving as a prognostic factor.
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。本研究的目的是研究血栓反应蛋白-1 的表达及其与预后的关系。
在这项回顾性研究中，通过基因表达谱分析和免疫组织化学，评估了原位癌（Tis）和晚期结膜 SCC（Tadv）中血栓反应蛋白-1 的表达、定位以及 Ki67 标记细胞指数。肿瘤细胞的细胞质和核染色的存在与否以及强度也分为 0-3 分，并进行半定量分析，以研究细胞内染色模式。还进一步研究了在一系列 31 例结膜 SCC 中，血栓反应蛋白-1 表达与肿瘤进展之间的关系。
队列中的 31 例患者（100%）均为东亚人。Tis 和 Tadv 之间的简单比较显示，包括血栓反应蛋白-1在内的 45 个基因的表达存在显著差异（p<0.01）。在本队列中，31/31 例肿瘤均为阳性（96%）表达血栓反应蛋白-1。此外，核和细胞质染色的血栓反应蛋白-1细胞内染色模式分析评分分别为 2.12 和 0.96，Tis 和 Tadv 之间存在显著差异（p<0.01）。Ki67 标记指数的改变与血栓反应蛋白-1细胞质评分显著相关（p=0.030）。此外，单因素 Cox 回归分析显示，血栓反应蛋白-1染色与无进展生存率（p=0.026）和最终眼眶内容物切除术（p=0.019）之间存在显著相关性。
本研究结果表明，血栓反应蛋白-1除了作为一个预后因素外，还是结膜 SCC 病理学的一个潜在分子靶点。
