RICARDO HSIEH
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Dermatologia, Faculdade de Medicina
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- The CDKN2A and MAP Kinase Pathways: Molecular Roads to Primary Oral Mucosal Melanoma(2013) HSIEH, Ricardo; NICO, Marcello M. S.; COUTINHO-CAMILLO, Claudia M.; BUIM, Marcilei E.; SANGUEZA, Martin; LOURENCO, Silvia V.The etiology and pathogenesis of oral mucosal melanomas are poorly understood, and no intraoral risk factors have been identified. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma-particularly changes in the CDKN2A (p16-cyclinD-Cdk-pRb) and MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2 proteins). We examined the central components of the CDKN2A and RAS-RAF-MEK-ERK cascades by immunohistochemistry in a series of 35 primary oral melanomas by tissue microarray (TMA). We noted altered expression of the CDKN2A cascade proteins, although these modulations did not correlate significantly with clinical and pathological parameters. The expression of MAP kinase cascade proteins changed in most cases. We observed that 28.57% of cases were RAS-positive and that 82.85% and 74.28% of cases were positive for BRAF and ERK2, respectively; MEK2 and ERK1 were not expressed in 48.57% and 80% of cases, and all cases were negative for MEK1. The absence of RAS and ERK1 and positivity for BRAF and ERK2 were associated with higher histological grade, vascular invasion, and metastasis. Expression of MEK2 was significantly linked to vascular invasion (P = 0.043). The CDKN2A and MAPK pathways require further study in mucosal melanomas, but our results highlight the significance of important alterations, particularly with regard to histological indicators of poor prognosis in primary oral mucosal melanomas, independent of UV exposure.
- Actionable Mutation Profile of Sun-Protected Melanomas in South America(2022) HSIEH, Ricardo; NICO, Marcello M. S.; CAMILLO, Claudia M. C.; OLIVEIRA, Katia K.; CARRARO, Dirce M.; SANGUEZA, Martin; V, Silvia LourencoMelanomas that arise in sun-protected sites, including acral and oral mucosal melanomas, are likely under the control of unique, specific mechanisms that lead to mutagenesis through various pathways. In this study, we examined somatic mutations in tumors by targeted sequencing using a custom Ion Ampliseq Panel, comprising hotspots of 14 genes that are frequently mutated in solid tumors. Tumor DNA was extracted from 9 formalin fixation, paraffin-embedded sun-protected melanomas (4 primary oral mucosal melanomas and 5 acral lentiginous melanomas), and we identified mutations in the NRAS, PIK3CA, EGFR, HRAS, ERBB2, and ROSI genes. This study reveals new actionable mutations that are potential targets in the treatment of photo-protected melanomas. Additional studies on more of these melanoma subtypes could confirm our findings and identify new mutations.
- Head and Neck Mucosal Melanoma: A Review(2014) LOURENCO, Silvia V.; FERNANDES, Juliana D.; HSIEH, Ricardo; COUTINHO-CAMILLO, Claudia M.; BOLOGNA, Sheyla; SANGUEZA, Martin; NICO, Marcello M. S.Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%-3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis.
- Adhesion Molecules in Primary Oral Mucosal Melanoma: Study of Claudins, Integrins and Immunoglobulins in a Series of 35 Cases(2013) BOLOGNA, Sheyla Batista; NICO, Marcello Menta S.; HSIEH, Ricardo; COUTINHO-CAMILLO, Claudia Malheiros; BUIM, Marcilei E.; FERNANDES, Juliana Dumet; SANGUEZA, Martin; SOARES, Fernando Augusto; LOURENCO, Silvia VanessaPrimary oral mucosal melanoma is a rare aggressive tumor. Recent studies have demonstrated a correlation between increased tumor invasion and the metastatic phenotype and altered adhesion molecule expression profiles. The present study analyzed the expression of integrins, claudins, and immunoglobulin-like adhesion molecules in oral mucosal melanomas and correlated results with clinical parameters. Immunohistochemical analyses of the expression patterns of these molecules were performed on thirty-five cases of primary oral mucosal melanomas organized in a tissue microarray. The results were correlated with clinical and histological features of the cohort. A number of integrin subunits were negative and this was related with vascular invasion. Positivity of integrin beta-3 and CD166 (activated leukocyte cell adhesion molecule) was statistically associated with extensive vascular invasion (P < 0.05). Lower expression of CD54 (intercellular cell adhesion molecule) was associated with cases with extensive necrosis. Most cases with metastatic disease were negative for CD66 (carcinoembryonic antigen-related cell adhesion molecule). Several subunits of claudins were negative and, although not statistically significant, this lack of expression was partially associated with histological factors of poor prognosis. Altered patterns of adhesion molecule expression, mainly integrins and immunoglobulin-like proteins, may participate in the pathogenesis and outcome of oral mucosal melanomas.
- Establishment and Characterization of an Oral Mucosal Melanoma Cell Line (MEMO) Derived From a Longstanding Primary Oral Melanoma(2013) LOURENCO, Silvia V.; BOLOGNA, Sheyla B.; HSIEH, Ricardo; SANGUEZA, Martin; FERNANDES, Juliana D.; NICO, Marcello M. S.Oral mucosal melanoma is rare. Its incidence peaks between 41 and 60 years of age; male/female ratio is 2:1. Preferred oral sites include hard palate and maxillary gingiva. Risk factors have not been clearly identified, but pigmented lesions may be present before the diagnosis of oral melanoma. We report an unusual case of oral mucosal melanoma of long-standing duration on hard palate and maxillary alveolar ridge in a male patient. Histopathologic features confirmed the diagnosis of invasive melanoma with a prominent in situ component. A cell lineage derived from the tumor was established and characterized, with phenotypic markers of melanocytes.