Jolique A van Ipenburg1, Nadine E de Waard2, Nicole C Naus3, Martine J Jager2, Dion Paridaens3,4, Robert M Verdijk1,4,5. 1. Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands. 2. Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands. 3. Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, The Netherlands. 4. The Rotterdam Eye Hospital, Rotterdam, The Netherlands. 5. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
Purpose: Chemokines play a role in the progression and metastatic spread of both cutaneous and uveal melanomas. The aim of this study was to examine the prognostic value of expression of chemokine receptors CCR7, CXCR4, and CCR10 in conjunctival melanocytic lesions. Methods: In total, 44 conjunctival nevi, 21 cases of primary acquired melanosis (PAM) with atypia and 35 conjunctival melanomas, were included. After immunohistochemical staining for CCR7, CXCR4, and CCR10 the immunoreactive score (IRS) was determined. The findings were correlated for association with melanoma and development of metastasis. For mechanistic evaluation, we used a mouse melanoma metastasis model using two human conjunctival melanoma cell lines, CM2005.1 and CRMM1. Results: All tested chemokines showed a significantly higher expression in conjunctival melanoma than conjunctival nevi. There was a statistically significant difference between the IRS in nevi and PAM with atypia for nuclear IRS in CCR10 (P = 0.03) and both nuclear and cytoplasmic IRS in CXCR4 (P < 0.01 and P = 0.03, respectively); this was also true evaluating the groups PAM with atypia and melanoma all together (P < 0.01). Furthermore, a trend for lower IRS was seen in cases of melanoma without metastasis, with a suggestive pattern of a higher IRS in cases that did develop metastases, supported for CXCR4 using the mouse melanoma metastasis model. Conclusions: Expression of specific chemokines changes during the progression and metastatic spread of conjunctival melanocytic lesions. Differential chemokine profiles may hold prognostic value for patients with conjunctival melanomas and might be considered as a therapeutic target.
Purpose: Chemokines play a role in the progression and metastatic spread of both cutaneous and uveal melanomas. The aim of this study was to examine the prognostic value of expression of chemokine receptors CCR7, CXCR4, and CCR10 in conjunctival melanocytic lesions. Methods: In total, 44 conjunctival nevi, 21 cases of primary acquired melanosis (PAM) with atypia and 35 conjunctival melanomas, were included. After immunohistochemical staining for CCR7, CXCR4, and CCR10 the immunoreactive score (IRS) was determined. The findings were correlated for association with melanoma and development of metastasis. For mechanistic evaluation, we used a mousemelanoma metastasis model using two humanconjunctival melanoma cell lines, CM2005.1 and CRMM1. Results: All tested chemokines showed a significantly higher expression in conjunctival melanoma than conjunctival nevi. There was a statistically significant difference between the IRS in nevi and PAM with atypia for nuclear IRS in CCR10 (P = 0.03) and both nuclear and cytoplasmic IRS in CXCR4 (P < 0.01 and P = 0.03, respectively); this was also true evaluating the groups PAM with atypia and melanoma all together (P < 0.01). Furthermore, a trend for lower IRS was seen in cases of melanoma without metastasis, with a suggestive pattern of a higher IRS in cases that did develop metastases, supported for CXCR4 using the mousemelanoma metastasis model. Conclusions: Expression of specific chemokines changes during the progression and metastatic spread of conjunctival melanocytic lesions. Differential chemokine profiles may hold prognostic value for patients with conjunctival melanomas and might be considered as a therapeutic target.
Authors: Wojtek Drabarek; Job van Riet; Josephine Q N Nguyen; Kyra N Smit; Natasha M van Poppelen; Rick Jansen; Eva Medico-Salsench; Jolanda Vaarwater; Frank J Magielsen; Tom Brands; Bert Eussen; Thierry P P van den Bosch; Robert M Verdijk; Nicole C Naus; Dion Paridaens; Annelies de Klein; Erwin Brosens; Harmen J G van de Werken; Emine Kilic Journal: Cancers (Basel) Date: 2022-02-08 Impact factor: 6.639
Authors: Neele Babst; Lisa K Isbell; Felix Rommel; Aysegul Tura; Mahdy Ranjbar; Salvatore Grisanti; Cordula Tschuch; Julia Schueler; Soroush Doostkam; Peter C Reinacher; Justus Duyster; Vinodh Kakkassery; Nikolas von Bubnoff Journal: Int J Mol Sci Date: 2022-10-04 Impact factor: 6.208