Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma

Background The aim of the study was to determine the concentration of endogenous cystatin C and cystatin SN, as potential tumor biomarkers, in the serum and biological fluids of the eye in both healthy controls and patients with uveal melanoma. Patients and methods The concentration of both cystatins was determined in the intraocular fluid (IOF), tear fluid, and serum of patients with uveal melanoma and compared to baseline measurements in IOF, tears, serum, cerebral spinal fluid, saliva and urine of healthy controls. Results The concentration of cystatin C in all the biological matrices obtained from healthy controls significantly exceeded the concentration of cystatin SN and was independent of gender. Cystatin C concentrations in the tear fluid of patients with uveal melanoma (both the eye with the malignancy, as well as the contralateral, non-affected eye), were significantly greater than cystatin C concentrations in the tear fluid of healthy controls and was independent of tumor size. The concentration of cystatin SN in IOF of patients with uveal melanoma was significantly less than the corresponding concentration of cystatin SN in healthy controls. Conclusions The ratio of cystatins (CysC:CysSN) in both the serum and tear fluid, as well as the concentration of cystatin SN in IOF, would appear to strongly suggest the presence of uveal melanoma. It is further suggested that multiple diagnostic criteria be utilized if a patient is suspected of having uveal melanoma, such as determination of the cystatin C and cystatin SN concentrations in serum, tears, and IOF, ocular fundus and ultrasound imaging, and biopsy with histopathological evaluation.

Epigenetic Changes in Malignant Uveal Melanoma and Possibilities of Their Therapeutic Targeting

Uveal melanoma (UM) is a deadly cancer that leads to metastatic disease in more than 50 % of the patients. Despite the improvement in the treatment of primary disease, there is still no effective therapy to prevent the development of metastases. Therefore, the disease requires intensive research to identify new treatment strategies. In preclinical UM models, epigenetic drugs have been shown to increase the sensitivity of resistant tumour cells to treatment. The successful use of histone deacetylase inhibitors, which induced cell cycle arrest, reprogramming consistent with melanocyte differentiation and inhibition of tumour growth in preclinical models, demonstrates the role of epigenetic regulation in UM metastasis. Identification of epigenetic changes associated with UM development an progression could contribute to the discovery of more effective drugs that, in combination with traditional approaches, may yield better therapeutic results for high-risk patients.

The Importance of Pet/Ct Examination in Patients With Malignant Uveal Melanoma

Introduction: Diagnostic and therapeutic management of the patient with malignant uveal melanoma (MMU) is subject to ongoing efforts to innovate. PET/CT (Positron Emission Tomography / Computed Tomography) examination is important in both diagnosis and metastases. Material and methods: Evaluation of the importance of PET/CT examination in the group of patients diagnosed with MMU in the period 12.1.2016 to 6.12.2018. All patients with a diagnosis of secondary retinal detachment, suspected uveal melanoma, underwent standard examinations to detect possible metastases (liver ultrasound, chest X-ray). Patients for whom a stereotactic radiosurgery solution was planned due to the stage of the disease this examination was to exclude metastasis in the liver or lungs. PET/CT examination is part of the protocol within the exclusion criteria for treatment with stereotactic radiosurgery in one day session surgery. Results: In the group of 84 patients, 47 women (56 %) and 37 men (44 %) were aged between 26 and 90 years. Their average age was 61.4 years. The median group was 64 years, modus 65 years. Of 84 patients, 79 (94 % of cases) had a diagnosis of C69.3 (choroidal melanoma) and 5 patients (6 % of cases) had a diagnosis of C69.4 (ciliary body melanoma). Subsequent PET/CT examination in many patients did not reveal hypermetabolic manifestations that could involve various pathological processes, in others the radiopharmaceutical was captured in the primary tumor area of the uveal tract. Hypermetabolism in eye globe was only found in melanomas with a volume of more than 0.5 cm3. PET/CT examinations were 85, with one patient undergoing examination twice. However, in 25 patients (26 examinations), the radiopharmaceutical was taken up in places that subsequently required closer attention. The initial aim of the examination was to locate possible metastases of MMU. In the others, 3 incidents have been reported: increased metabolism in the lung and liver, thyroid and mediastinal lymph nodes. Of the 85 examinations, 26 (30.6 %) resulted in a hypermetabolic manifestation of accumulation, which was not located in the eye tract, resp. right in the eye. Two malignancies (prostatic carcinoma and rectosigmal carcinoma) have occurred in two patients. Very important was the discovery of MMU metastasis in the liver, which confirmed the important role of PET/CT examination in the management of MMU patients. The metastasis was discovered after repeated PET/CT examination. Conclusion: PET/CT examination is a technically demanding examination and is one of the possibilities of imaging intraocular melanoma in tumors with volume more than 0.5 cm3. It is important in determining the grading and staging of the disease before radiosurgical treatment and also in detecting possible metastases after MMU treatment in cases where ultrasound or MRI examinations do not give a definite result. However, our study confirmed the significance of this examination for randomly detected 2 duplex malignancies (2.4%) and 3 incidentalomas (3.6%) in patients whose ophthalmologist diagnosed uveal melanoma and sent patients for full-body PET/CT examination.