Morphological features of the distribution of extracellular matrix components MMP-9 and type IV collagen in metastatic choroidal melanoma

Abstract

Introduction. Early diagnosis and prediction of distant metastases in choroidal melanoma patients based on morphological and IHC assessment of the components of the tumor microenvironment is a topical issue. The aim was to evaluate the IHC expression of MMP-9 and type IV collagen in metastatic choroidal melanoma. Materials and methods. We analyzed 43 cases of choroidal melanoma T2(a,b,c)-3N0M0-1 during 2013–2017. The patients were divided into two groups: group 1 included patients with primary choroidal melanoma without distant metastases (N=25) and group 2 included patients with primary choroidal melanoma with distant liver metastases (N=18). We performed an IHC assay of the surgical samples with MMP-9 (Poly) (MMP-9) and Collagen-IV (Clone CIV 22) (Col4) antibodies. Qualitative, semi-quantitative, and quantita-tive parameters were evaluated with digital pathology software. We developed a semi-quantitative method for estimating the intensity of IHC expression of these markers (in scores) in choroidal melanoma. Results. The study included 22 female and 21 male patients (51.2% and 48.8%, respectively), the average age being 60.5 years. The thickness of choroidal melanoma averaged 8.3 mm; the average diameter of the tumor was 12.3 mm. We detected strong MMP-9 expression in tumor cells and their microenvironment and remodeled collagen framework in tumors with pronounced tumor necrosis, thickness, and scleral involve-ment. A more pronounced expression of MMP-9 was associated with an increase in isolated type IV collagen fibers in the extracellular matrix (ECM) of the metastatic choroidal melanoma. Conclusion. During the growth and progression of choroidal melanoma, the components of the microenvi-ronment and tumor cells have a mutual effect with the disorganization of ECM components. Indicators of IHC expression (MMP-9, Col4) in a tumor should not be considered as a diagnostic marker of metastatic choroidal melanoma. However, they can be used in clinical practice when monitoring the course of the disease and in studying the mechanisms of remodeling of the tumor microenvironment. Keywords: choroidal melanoma, MMP-9, type IV collagen, metastasis