Novel Prognostic Immunohistochemical Markers in Uveal Melanoma-Literature Review

Gajdzis, Małgorzata; Kaczmarek, Radosław; Gajdzis, Paweł

doi:10.3390/cancers13164031

Cited by 7 publications

(5 citation statements)

References 101 publications

(232 reference statements)

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“…The potential prognostic value of various kinds of protein expression by immunohistochemistry has been explored. 45 Nuclear BAP1 immunostaining showed a significant correlation with the survival rate of UM cases. 46 Our study indicates that PTK2 protein expression may be a prognostic factor in UM and used to predict patient prognosis.…”

Section: Discussionmentioning

confidence: 86%

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PTK2 promotes uveal melanoma metastasis by activating epithelial‐to‐mesenchymal transition

et al. 2023

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Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. More than half of UM cases develop distant metastasis to the liver, lung, bone, and other organs, which frequently results in patient death. However, the mechanisms underlying UM metastasis remain largely unknown. Here, we report that protein tyrosine kinase 2 (PTK2), a nonreceptor protein tyrosine kinase also known as focal adhesion kinase (FAK), was overexpressed in most examined UM specimens. Furthermore, we identified PTK2 expression as a novel independent risk factor that predicts poor prognosis of UM patients. Mechanistic studies revealed that PTK2 promotes the EMT phenotype, leading to metastasis of UM cells. We showed that PTK2, located on chromosome 8q, is a functional gene of chromosome 8q gain to UM metastasis, which may represent the molecular mechanism for the aberrant expression and activation of PTK2 in UM. Our data reveal a novel role and mechanism of PTK2 in the metastatic process of UM, suggesting PTK2 may be a potential prognostic biomarker for UM metastasis and a promising therapeutic target for UM treatment.

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Section: Discussionmentioning

confidence: 86%

“…Immunohistochemistry is a powerful laboratory technique that has revolutionized pathology over the past decades. The potential prognostic value of various kinds of protein expression by immunohistochemistry has been explored 45 . Nuclear BAP1 immunostaining showed a significant correlation with the survival rate of UM cases 46 .…”

Section: Discussionmentioning

confidence: 99%

PTK2 promotes uveal melanoma metastasis by activating epithelial‐to‐mesenchymal transition

et al. 2023

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“…Currently, there is no effective pharmacological treatment for patients with UM and the research on new biomarkers, which can serve as a prognostic factors or a potential target in anti‐cancer therapy may be crucial for favorable long‐term survival for UM patients (Gajdzis et al, 2021). The proteins, such as adiponectin, CD147, c‐Met, COX‐2, EGFR, and others were identified previously as possible useful prognostic markers in UM (Gajdzis et al, 2021). However, despite these results, the identification of new prognostic tissue markers for UM is still a significant challenge for the scientific community.…”

Section: Discussionmentioning

confidence: 99%

Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study

Taskaeva,

Shatruk,

Bgatova

et al. 2023

Microscopy Res & Technique

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Uveal melanoma is an ocular tumor with a high risk of developing metastases. The endo‐lysosomal system can affect the melanoma progression by accelerating and facilitating invasion or metastasis. This study aims to conduct comparative analysis of normal choroidal melanocytes and uveal melanoma cells ultrastructure with a focus on intracellular transport system, and to examine the patterns of autophagy‐ and vesicular trafficking‐related proteins expression in a case series of uveal melanomas. Transmission electron microscopy was used to assess the ultrastructure of normal choroidal melanocytes and uveal melanoma cells. The expression levels of autophagy‐ and vesicular trafficking‐related proteins in three histological types of uveal melanoma were analyzed by immunofluorescence staining. Electron microscopy results showed that the autophagic vacuoles were more abundant in normal choroidal melanocytes, than in uveal melanoma cells. The normal choroidal melanocytes were characterized by active intracellular vesicular trafficking; however, the proportion of caveolae was higher in uveal melanoma cells. The spindle type of tumor was characterized by a high expression levels of LC3 beta, while Rab7 and Rab11 proteins expression was significantly up‐regulated in the mixed‐type tumor cells. The results indicate that uveal melanoma cells probably have lower basal levels of autophagy and higher receptor‐mediated endocytic trafficking‐associated with caveolae than normal choroidal melanocytes.Research Highlights The autophagic vacuoles are abundant in normal choroidal melanocytes. Uveal melanoma cells are characterized by a high proportion of caveolae. The high expression levels of LC3 beta were revealed in a spindle type of tumor, while Rab7 and Rab11 proteins expression was up‐regulated in the mixed‐type tumor cells.

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“…For instance, loss of nuclear BAP1 staining was linked to an 8-fold higher risk of developing metastases [31]. Malgorzata et al focused exclusively on biomarkers assessed through IHC, reporting 55 of such molecules that correlate with a multitude of clinicopathological parameters and affecting patients' outcome [32].…”

Section: Discussionmentioning

confidence: 99%

EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia

et al. 2022

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Uveal melanomas (UMs) comprise the most common primary intraocular malignancies in adults, with the eye representing the second most common site for melanoma, following the skin. Prognosis remains poor, with approximately half of the cases presenting with metastatic disease at the time of diagnosis. Erythropoietin-producing human hepatocellular receptors (EPHs) comprise the largest known family of tyrosine receptors, in which, along with their ligands, ephrins, play an important role in a plethora of processes in human physiology, and are implicated in key steps of carcinogenesis. In the present study, EPHA2, EPHA4, and EPHA6 immunohistochemical expressions were investigated in UM tissues and further correlated to a multitude of clinicopathological parameters, including disease stage and patients’ overall survival (OS). High levels of EPHA2 expression were significantly associated with increased tumor vertical thickness (p = 0.03) and the presence of intrascleral involvement (p = 0.05), whereas high EPHA6 nuclear expression was associated with older age at diagnosis (p = 0.03) and absence of retinal detachment (p = 0.05). In a multivariate survival analysis, increased EPHA4 expression was associated with shortened OS along with the presence of metastasis (p < 0.001) and monosomy 3 (p = 0.02). In a separate model, the concurrent overexpression of at least two of the investigated EPHs (HR = 14.7, p = 0.03) also proved to be an independent poor prognostic factor. In conclusion, our results implicate these specific members of the EPHA group as potential biomarkers for disease prognosis as well as possible targets for the development of novel therapeutic interventions.

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Novel Prognostic Immunohistochemical Markers in Uveal Melanoma-Literature Review

Cited by 7 publications

References 101 publications

PTK2 promotes uveal melanoma metastasis by activating epithelial‐to‐mesenchymal transition

PTK2 promotes uveal melanoma metastasis by activating epithelial‐to‐mesenchymal transition

Autophagy and vesicular trafficking in human uveal melanoma: A histopathological study

EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia

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