Kakkassery Vinodh, Wirtz Christoph, Schargus Marc, Grisanti Salvatore, Tura Aysegül, Ranjbar Mahdy, Dick H Burkhard, Reinehr Sabrina, Joachim Stephanie C
Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany;
Department of Ophthalmology, University of Lübeck, Lübeck, Germany.
In Vivo. 2021 Nov-Dec;35(6):3603-3612. doi: 10.21873/invivo.12666.
BACKGROUND/AIM: Conjunctival malignant melanoma (CMM) is a rare, but very aggressive tumor with a high metastasis rate. Not much is known about the CMM metastasis mechanisms. So far, epidermal growth factor (EGF) and its receptor (EGF-R) as well as macrophages and matrix metalloproteinase 9 (MMP-9) have been reported to lead to metastasis by epithelial-mesenchymal-transition and tumor migration in different solid tumors. Therefore, we evaluated whether EGF and EGF-R, CD68 and MMP-9 are altered in CMM samples in comparison to conjunctival nevi and healthy conjunctiva.
EGF, EGF-R, the macrophage marker CD68 and MMP-9 expression were analyzed in human conjunctival melanoma (CMM, n=16), human conjunctival nevi (n=13) and disease-free human conjunctiva (controls, n=14) by immunohistology. Staining of each sample was evaluated using a standardized score ranging from negative (0) to triple positive (3). The groups were then compared by ANOVA, followed by Tukey's post-hoc test.
A statistically significant increase of EGF was seen in CMM samples in comparison to conjunctival nevi (p=0.03). In contrast, no statistically significant differences in EGF-R expression were noted between the three groups. A statistically significant increase of CD68 was only seen in conjunctival nevi compared to controls (p=0.04). MMP-9 expression was similar in all groups.
In CMM, the study data demonstrated an up-regulation of EGF in comparison to conjunctival nevi. Hence, EGF might promote proliferation of CMM cells and induce the epithelial-mesenchymal transition. Therefore, our data suggest that an interplay between EGF and CMM might have a critical role in the developing CMM tumors and metastasis.
背景/目的:结膜恶性黑色素瘤(CMM)是一种罕见但极具侵袭性的肿瘤,转移率很高。关于CMM的转移机制知之甚少。迄今为止,表皮生长因子(EGF)及其受体(EGF-R)以及巨噬细胞和基质金属蛋白酶9(MMP-9)已被报道在不同实体瘤中通过上皮-间质转化和肿瘤迁移导致转移。因此,我们评估了与结膜痣和健康结膜相比,CMM样本中EGF和EGF-R、CD68和MMP-9是否发生改变。
通过免疫组织学分析人结膜黑色素瘤(CMM,n = 16)、人结膜痣(n = 13)和无病的人结膜(对照组,n = 14)中EGF、EGF-R、巨噬细胞标志物CD68和MMP-9的表达。使用从阴性(0)到三阳性(3)的标准化评分评估每个样本的染色情况。然后通过方差分析对各组进行比较,随后进行Tukey事后检验。
与结膜痣相比,CMM样本中EGF有统计学意义的增加(p = 0.03)。相比之下,三组之间EGF-R表达没有统计学意义的差异。与对照组相比,仅在结膜痣中观察到CD68有统计学意义的增加(p = 0.04)。所有组中MMP-9表达相似。
在CMM中,研究数据表明与结膜痣相比EGF上调。因此,EGF可能促进CMM细胞增殖并诱导上皮-间质转化。因此,我们的数据表明EGF与CMM之间的相互作用可能在CMM肿瘤的发生和转移中起关键作用。