Vinodh Kakkassery1,2, Christoph Wirtz3, Marc Schargus3,4,5, Salvatore Grisanti2, Aysegül Tura2, Mahdy Ranjbar2, H Burkhard Dick3, Sabrina Reinehr3, Stephanie C Joachim3. 1. Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany; vinodh.kakkassery@gmail.com. 2. Department of Ophthalmology, University of Lübeck, Lübeck, Germany. 3. Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany. 4. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany. 5. Department of Ophthalmology, Asklepios Hospital Nord-Heidberg, Hamburg, Germany.
Abstract
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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Andreas Bracher; Ana Soler Cardona; Stefanie Tauber; Astrid M Fink; Andreas Steiner; Hubert Pehamberger; Heide Niederleithner; Peter Petzelbauer; Marion Gröger; Robert Loewe Journal: J Invest Dermatol Date: 2012-09-06 Impact factor: 8.551
Authors: Laura Hahn; Sarah Meister; Mareike Mannewitz; Susanne Beyer; Stefanie Corradini; Uwe Hasbargen; Sven Mahner; Udo Jeschke; Thomas Kolben; Alexander Burges Journal: Biomolecules Date: 2022-05-15