RESUMO
Uveal melanoma (UM) is an ocular tumor with a dismal prognosis. Despite the availability of precise molecular and cytogenetic techniques, clinicopathologic features with limited accuracy are widely used to predict metastatic potential. In 51 UM tissues, we assessed a correlation between the expression of nine proteins evaluated by immunohistochemistry (IHC) (Melan-A, S100, HMB45, Cyclin D1, Ki-67, p53, KIT, BCL2, and AIFM1) and the presence of UM-specific chromosomal rearrangements measured by multiplex ligation-dependent probe amplification (MLPA), to find IHC markers with increased prognostic information. Furthermore, mRNA expression and DNA methylation values were extracted from the whole-genome data, achieved by analyzing 22 fresh frozen UM tissues. KIT positivity was associated with monosomy 3, increasing the risk of poor prognosis more than 17-fold (95% CI 1.53-198.69, p = 0.021). A strong negative correlation was identified between mRNA expression and DNA methylation values for 12 of 20 analyzed positions, five located in regulatory regions of the KIT gene (r = -0.658, p = 0.001; r = -0.662, p = 0.001; r = -0.816; p < 0.001; r = -0.689, p = 0.001; r = -0.809, p < 0.001, respectively). DNA methylation ß values were also inversely associated with KIT protein expression (p = 0.001; p = 0.001; p = 0.015; p = 0.025; p = 0.002). Our findings, showing epigenetic deregulation of KIT expression, may contribute to understanding the past failure to therapeutically target KIT in UM.
Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Uveais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Prognóstico , Neoplasias Uveais/patologia , Neoplasias Uveais/terapiaRESUMO
Despite outstanding advances in diagnosis and the treatment of primary uveal melanoma (UM), nearly 50% of UM patients develop metastases via hematogenous dissemination, driven by the epithelial-mesenchymal transition (EMT). Despite the failure in UM to date, a liquid biopsy may offer a feasible non-invasive approach for monitoring metastatic disease progression and addressing protracted dormancy. To detect circulating tumor cells (CTCs) in UM patients, we evaluated the mRNA expression of EMT-associated transcription factors in CD45-depleted blood fraction, using qRT-PCR. ddPCR was employed to assess UM-specific GNA11, GNAQ, PLCß4, and CYSLTR2 mutations in plasma DNA. Moreover, microarray analysis was performed on total RNA isolated from tumor tissues to estimate the prognostic value of EMT-associated gene expression. In total, 42 primary UM and 11 metastatic patients were enrolled. All CD45-depleted samples were negative for CTC when compared to the peripheral blood fraction of 60 healthy controls. Tumor-specific mutations were detected in the plasma of 21.4% patients, merely, in 9.4% of primary UM, while 54.5% in metastatic patients. Unsupervised hierarchical clustering of differentially expressed EMT genes showed significant differences between monosomy 3 and disomy 3 tumors. Newly identified genes can serve as non-invasive prognostic biomarkers that can support therapeutic decisions.
Assuntos
Biomarcadores Tumorais/genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , Células Neoplásicas Circulantes/patologia , Neoplasias Uveais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Deleção Cromossômica , Cromossomos Humanos Par 3/genética , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Biópsia Líquida , Masculino , Melanoma/secundário , Melanoma/terapia , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Neoplasias Uveais/secundário , Neoplasias Uveais/terapiaRESUMO
Introduction: The treatment of iridociliary and choroidal melanoma relies on the patient's systemic health, tumor size, location, related features, state of the opposing eye, and personal preferences. The two categories are radiation and surgical techniques. Transpupillary thermotherapy, plaque radiotherapy, charged particle irradiation, local resection, enucleation, orbital exenteration, and experimental nanoparticle therapy are all options for treating choroidal melanoma. Case Presentation: The method that entails creating a partial thickness circular, rectangular, or polyhedral scleral flap in the region covering the tumor after removing a portion of the extraocular muscles is the most popular method for local excision in choroidal or choroidal-ciliary body cancers. We discuss our experience treating iridociliary melanoma using block excision and stereotactic irradiation on a linear accelerator with TD 20.0 Gy. Conclusion: One of the treatment modalities is the combined treatment approach using stereotactic irradiation and tumor resection, and our results 1 year after therapy are comparable to the rates of local control and anatomic eye preservation to those achieved in studies of comparable uveal melanoma treatment modalities.
RESUMO
The report aims to present the case of intraocular leiomyoma. We conducted a case study on a patient who presented with an intraocular tumour. After examination, including magnetic resonance, positron emission tomography with computed tomography, B-scan, we performed surgery - enucleation of the eye globe with histological verification of tumour mass. Histological analysis of enucleated eyes proved intraocular leiomyoma. Leiomyoma is a rare intraocular tumour, which is clinically challenging to recognize; therefore, histological confirmation is most often required.
RESUMO
BACKGROUND: The purpose of this article is to evaluate the positivity of conjunctival sac swab by PCR (Polymerase chain reaction) test in COronaVIrus Disease 19 (COVID-19) patients. METHODS: Inclusion criteria of our study were COVID-19 patients hospitalized during March 2021 in inpatient wards at University Hospitals in towns Bratislava and Zilina, Slovakia. The conjunctival sac swabs collected by four ophthalmologists were stored for 24 h, then analyzed in the laboratory of the Department of Microbiology and Immunology, Jessenius Faculty of Medicine in Martin, Comenius University, Slovakia. The sampling apparatus, used for conjunctival sac swab, was the Dacron polyester swab. RESULTS: We examined one group of 302 COVID-19 patients, 168 Male (56%) and 134 Female (44%). The patients' mean age was 66.3 ± 13.66 years, ranging from 25 to 96 years, and the mean length of hospital stay in our patients with a nasopharyngeal positive PCR test was 7.33 ± 4.76, from 2 to 24 days. The PCR tests from the conjunctival sac swabs were positive in 33 patients (11%), negative in 259 patients (86%), and ten patients (3%) were with the unclear result. In the group of 33 positive patients were 17 males with a mean age of 74.6 ± 13.59 years and 16 females with a mean age of 70.63 ± 14.17 years. The cycle threshold (CT) values differed significantly between conjunctival sac swabs from the nasopharynx and the conjunctiva. Medians of the values were 25.1 (14.1, 32.1) and 31.5 (22.6, 36.6) (P < 0.001), respectively. CONCLUSION: This study affirmed that in COVID-19 patients the SARS-CoV-2 was detectable with PCR test in conjunctival sac swab, but the positivity rate was only about one to ten cases (11%).