RESUMO
Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model's performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.
RESUMO
INTRODUCTION AND OBJECTIVE: The aim of the present study is the immunohistochemical assessment of tumor progression markers (E-cadherin, β-catenin, CEACAM-1 and PTEN) in primary cutaneous melanomas and their correlation with prognostic factors. METHOD: Primary lesions in patients with cutaneous melanoma were recorded as to clinical data (age, gender, location and metastases) and anatomopathologic data (Breslow, Clark level, margins, histological type, mitosis, ulceration, regression, satellitosis and TIL type). It was made a comparison between immunohistochemical expression of the markers and prognostic and anatomopathologic factors. RESULTS: Breslow thickness was > 1 mm (thick) in 21 patients (48.83 percent) and < 1 mm (thin) in 22 (51.16 percent). There was a higher CEACAM-1 positive expression in thick melanomas than in thin ones (p = 0.002). There was a more frequent E-cadherin (p = 0.008), b-catenin (p = 0.001) and PTEN (p = 0.005) positive expression in thin melanomas than in thick ones. There was a more frequent CEACAM-1 positive expression in superficial (p = 0.003) and deep (p = 0.002) samples of thick melanomas than in thin ones. No statistically significant differences between clinical and histopathological data were found when comparing patients with (n = 6) and without metastasis (n = 15). DISCUSSION AND CONCLUSION: There was a higher positivity for E-cadherin, b-catenin and PTEN in thin melanomas, whereas there was a higher positivity for CEACAM-1 in thick melanomas.
INTRODUÇÃO E OBJETIVO: O objetivo do presente estudo está na avaliação imuno-histoquímica de marcadores de progressão tumoral (E-caderina, β-catenina, CEACAM-1 e PTEN) em melanomas cutâneos primários e sua correlação com fatores prognósticos. MÉTODO: Lesões primárias de pacientes portadores de melanoma cutâneo foram tabuladas quanto a dados clínicos (idade, sexo, localização e metástases) e anatomopatológicos (Breslow, nível de Clark, margens, tipo histológico, mitoses, ulceração, regressão, satelitose e tipo de TIL). Foi realizada comparação da expressão imuno-histoquímica dos marcadores em estudo com fatores prognósticos clínicos e anatomopatológicos. RESULTADOS: Breslow foi > 1 mm (espesso) em 21 pacientes (48,83 por cento) e ≤ 1 mm (fino) em 22 (51,16 por cento). CEACAM-1 foi mais positivo em melanomas grossos que em finos (p = 0,002). E-caderina (p = 0,008), β-catenina (p = 0,001) e PTEN (p = 0,005) foram mais frequentemente positivos em melanomas finos que em grossos. CEACAM-1 foi mais frequentemente positivo nas porções superficiais (p = 0,003) e profundas (p = 0,002) dos melanomas grossos que nas dos finos. Não houve diferenças estatisticamente significativas entre dados clínicos e histopatológicos quando comparamos os pacientes com (n = 6) e sem (n = 15) metástases. DISCUSSÃO E CONCLUSÃO: Observou-se maior tendência de positividade para E-caderina, b-catenina e PTEN em melanomas finos. Por sua vez, CEACAM-1 demonstrou maior frequência de positividade nos melanomas grossos.
