Franz Regina, Ritter Nathalie, Hein Rüdiger, Biedermann Tilo, Al-Sisi Mohammed, Eyerich Kilian, Garzorz-Stark Natalie, Andres Christian
*Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany; and †Labor für Dermatohistologie, Munich, Germany.
Am J Dermatopathol. 2017 Oct;39(10):742-746. doi: 10.1097/DAD.0000000000000784.
As important players of the innate immune system, Toll-like receptors (TLRs) and their role for tumorigenesis have been in the focus of research. In particular TLR7 is an interesting candidate, as TLR7 agonists are broadly used for the treatment of cutaneous tumors. However, data addressing the baseline expression of TLR7 in both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) on the protein level are lacking, while on the genomic level significantly elevated expression of TLR7 in SCC but not in BCC has been demonstrated.
Our aim was to characterize the immunohistochemical staining pattern of TLR7 in SCC and BCC. Besides, we aimed to clarify if, in case of different TLR7 expression between SCC and BCC, TLR7 expression would help to define basosquamous carcinoma (BSC), a tumor entity sharing characteristics of both SCC and BCC.
We examined histopathological samples from 23 BCC, 4 BSC, and 24 SCC and characterized the expression of TLR7 by immunohistochemistry and immunofluorescence.
We found that TLR7 was not expressed by the tumor tissue of SCC, BCC, and BSC, but by inflammatory cells located within the tumoral and/or peritumoral tissue. Whereas the overall expression of TLR7 did not differ between BCC and SCC (30.4% vs. 45.8%, respectively), we found that within the group of SCC, the well-differentiated SCC showed strong tumoral and/or peritumoral immunocellular TLR7 reactivity in contrast to the poorly differentiated SCC (73.33% vs. 11.1%, respectively). Besides, immunofluorescence double staining revealed the expression of TLR7 in immune cells closely interacting with T cells and natural killer cells.
In contrast to genomic data, we did not find a general difference between baseline TLR7 expression of SCC and BCC on the protein level. Nevertheless, the expression of TLR7 by the inflammatory infiltrate associated with SCC may correlate with the degree of differentiation of SCC possibly indicating better outcome.
作为天然免疫系统的重要组成部分,Toll样受体(TLRs)及其在肿瘤发生中的作用一直是研究的焦点。特别是TLR7是一个有趣的候选对象,因为TLR7激动剂被广泛用于治疗皮肤肿瘤。然而,关于TLR7在基底细胞癌(BCC)和鳞状细胞癌(SCC)中蛋白质水平的基线表达的数据尚缺乏,而在基因组水平上,已证明SCC中TLR7表达显著升高,而BCC中则没有。
我们的目的是描述TLR7在SCC和BCC中的免疫组织化学染色模式。此外,我们旨在阐明,如果SCC和BCC之间存在不同的TLR7表达,TLR7表达是否有助于定义基底鳞状细胞癌(BSC),这是一种兼具SCC和BCC特征的肿瘤实体。
我们检查了23例BCC、4例BSC和24例SCC的组织病理学样本,并通过免疫组织化学和免疫荧光对TLR7的表达进行了表征。
我们发现SCC、BCC和BSC的肿瘤组织中未表达TLR7,但肿瘤内和/或肿瘤周围组织中的炎症细胞表达TLR7。虽然BCC和SCC之间TLR7的总体表达没有差异(分别为30.4%和45.8%),但我们发现在SCC组中,高分化SCC与低分化SCC相比,肿瘤和/或肿瘤周围免疫细胞TLR7反应性较强(分别为73.33%和11.1%)。此外,免疫荧光双重染色显示TLR7在与T细胞和自然杀伤细胞密切相互作用的免疫细胞中表达。
与基因组数据相反,我们在蛋白质水平上未发现SCC和BCC的基线TLR7表达存在普遍差异。然而,与SCC相关的炎症浸润中TLR7的表达可能与SCC的分化程度相关,这可能表明预后较好。