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
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- Immunoexpression of adhesion molecules during human fetal hair development(2020) SILVA, Laura Maria Andrade; HSIEH, Ricardo; LOURENCO, Silvia Vanessa; OTTONI, Veronica; VALENTE, Neusa; FERNANDES, Juliana DumetIntroduction. Hair follicles are produced in a cyclical manner and the machinery involved in the reproduction of these follicles is present since the fetal stage. Although extensive research has been done on the human hair follicle, very little is known about the importance of adhesion molecules in its development. Material and methods. We analyzed here, the immunoexpression of beta-1 integrin, p-cadherin, e-cadherin, and beta-catenin in hair follicles from 26 formalin-fixed and paraffin-embedded skin samples from human embryos and fetus between 12-23 weeks of gestational age. Results. The adhesion molecules beta-1 integrin and e-cadherin/p-cadherin were expressed from 12 weeks and seemed to play a role in regulating epidermis invagination. Beta-catenin immunostaining was negative in all cases; down regulation of this protein may be necessary for fetal hair development and thus facilitating hair follicle down growth. Discussion/Conclusion. Adhesion molecules are essential for hair follicle down growth and proliferation; integrins and cadherins play a major role in this process. More studies are needed to describe hair follicle development.
- Immunostaining study of cytokeratins in human hair follicle development(2020) SILVA, Laura Maria Andrade; HSIEH, Ricardo; LOURENCO, Silvia Vanessa; VALENTE, Neusa Yuriko Sakai; PAIVA, Geise Rezende; FERNANDES, Juliana DumetBackground: The hair follicle is a unique structure, one of the most dynamic structures in mammalians, which can reproduce in every new cycle all the mechanism involved in its fetal development. Although a lot of research has been made about the human hair follicle much less has been discovered about the importance of the cytokeratins (CKs) in its development. Objective: Study the immunohistochemical pattern of epithelial CKs during human hair follicle development. Methods: We performed an immunohistochemical study using fresh post-mortem skin biopsies of human fetuses between 4 and 25 weeks of gestational age to study the expression of cytokeratins (CKs): CK1, CK10, CK13, CK14, CK16 and CK20 during human hair follicle fetal development. Study limitations: Restrospective study with a good number of makers but with a small population. Results/conclusion: We found that, the CKs were expressed in an intermediate time during follicular development. The epithelial CKs (CK1, CK14, CK10, CK13) and the epithelial CKs witha proliferative character such as CK16 were expressed first, as markers of cellular maturation and follicular keratinization. At a later phase, CK20 was expressed in more developed primitive hair follicles as previously discussed in literature. (C) 2020 Sociedade Brasileira de Dermatologia.
- Epithelial-mesenchymal transition related to bone invasion in oral squamous cell carcinoma(2022) VANINI, Jaqueline Vaz; KOYAMA, Leonardo Kenji Sakaue; MATOS, Leandro Luongo de; FIGUEREDO JUNIOR, Jose Martins; CERNEA, Claudio Roberto; NAGANO, Cibele Pidorodeski; COUTINHO-CAMILLO, Claudia Malheiros; HSIEH, Ricardo; LOURENCO, Silvia VanessaIntroduction: Bone invasion is an important prognostic factor in oral squamous cell carcinoma, leading to a lower survival rate and the use of aggressive treatment approaches. Epithelial-mesenchymal transition (EMT) is possibly involved in this process, because it is often related to mechanisms of cell motility and invasiveness. This study examined whether a panel of epithelial-mesenchymal markers are present in cases of oral squamous cell carcinoma with bone invasion and whether these proteins have any relationship with patients' clinical-pathological parameters and prognostic factors. Methods: Immunohistochemical analysis of E-cadherin, twist, vimentin, TGF beta 1, and periostin was performed in paraffin-embedded samples of 62 oral squamous cell carcinoma cases. Results: The analysis revealed that most cases (66%) presented with a dominant tumor infiltrative pattern in bone tissue, associated with lower survival rates, when compared with cases with a dominant erosive invasion pattern (P = 0.048). Twenty-seven cases (43%) expressed markers that were compatible with total or partial EMT at the tumor-bone interface. There was no association between evidence of total or partial EMT and other demographic or prognostic features. E-cadherin-positive cases were associated with tobacco smoking (P = 0.022); vimentin-positive cases correlated with tumors under 4 cm (P = 0.043). Twistexpression was observed in tumors with a dominant infiltrative pattern (P = 0.041) and was associated with the absence of periostin (P = 0.031). Conclusion: We observed evidence of total or partial EMT in oral squamous cell carcinoma bone invasion. The transcription factor twist appears to be involved in bone invasion and disease progression. (C) 2022 The Authors.
- 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.
conferenceObject Primary oral mucosal melanoma: Are NRAS and BRAF mutations determinant in its pathogenesis?(2014) NICO, M. Menta S.; HSIEH, R.; CAMILLO-COUTINHO, C.; FERNANDES, J. Dumet; LOURENCO, S. V.- 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.
- Claudin expression is maintained in mucoepidermoid carcinoma of the salivary gland(2020) ARRUDA, Claudia Fabiana Joca de; COUTINHO-CAMILLO, Claudia Malheiros; MARQUES, Marcia Martins; NAGANO, Cibele Pidorodeski; BOLOGNA, Sheyla Batista; BETTIM, Barbara Beltrame; GERMANO, Janaina Naiara; PINTO, Clovis Antonio Lopes; HSIEH, Ricardo; LOURENCO, Silvia VanessaObjective: The aim of the present study was to investigate the expression of claudin-1,-3,-4,-5 and-7 proteins in mucoepidermoid carcinoma of oral cavity and analyze whether EGF may interfere in the expression of the genes that encode claudins using in vitro models. Material and methods: Using immunohistochemistry, the expression of claudins was searched in 36 histologically graded cases of mucoepidermoid carcinoma. The association of expression of claudins with clinical-pathological parameters was evaluated. An in vitro step investigated the influence of EGF on gene expression of claudins by real time RT-PCR technique. Results: Claudin-1,-3,-4,-5, and-7 were highly expressed in most mucoepidermoid carcinomas. These expres-sions were compared with clinicopathological parameters. High expression of claudin-1 was associated with patients over 40 years-old (p = 0.05) and Caucasians (p = 0.024). In vitro experiments demonstrated a tendency for Claudin gene expression increase after EGF stimulus. Conclusions: The expression of claudins is maintained in mucoepidermoid carcinoma cells and EGF could be related with this expression. Our results point out to a fundamental biological importance to CLDNs in normal and neoplastic tissue. The expression patterns of CLDNs does not yet allow a clinical application, but the biological knowledge will ground evidence to new studies towards possible target-therapies.
- 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.