SILVIA VANESSA LOURENCO
Projetos de Pesquisa
Unidades Organizacionais
ODE, FO - Docente
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina - Líder
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article 14 Citação(ões) na Scopus MAP Kinase Pathways: Molecular Roads to Primary Acral Lentiginous Melanoma(2015) FERNANDES, Juliana D.; HSIEH, Ricardo; FREITAS, Luiz A. R. de; BRANDAO, Miguel A. R.; LOURENCO, Silvia V.; SANGUEZA, Martin; NICO, Marcello M. S.The etiology and pathogenesis of lentiginous acral melanomas are poorly understood. Recent studies have postulated that DNA repair mechanisms and cell growth pathways are involved in the development of melanoma, particularly changes in the MAPK pathways (RAS, BRAF, MEK 1/2, and ERK 1/2). The aim of this study is to assess the status of the MAP kinase pathways in the pathogenesis of acral melanomas. The authors examined the components of the RAS-RAF-MEK-ERK cascades by immunohistochemistry in a series of 16 primary acral melanomas by tissue microarray. The expression of MAP kinase cascade proteins changed in most cases. The authors observed that 57.14% of cases were BRAF positive and that 61.53%, 71.42%, and 71.42% of cases were positive for MEK2, ERK1, and ERK2, respectively; RAS was not expressed in 92.31%, and all cases were negative for MEK1. The absence of RAS and positivity for MEK2, ERK1, and ERK2 were most seen in invasive cases with high thickness. These aspects of the MAPK pathway require further examination in acral melanomas between different populations. Nevertheless, the results highlight significant alterations in the MAP kinase cascades that are related to histological indicators of prognosis in primary acral melanomas.- Metastasis to the Oral Cavity: Report of 12 Cases(2022) V, Silvia Lourenco; FLOREZI, Giovanna P.; SMITTER, Anabel S.; BOLOGNA, Sheyla B.; NICO, Marcello M. S.Oral cavity is not a common route for metastatic dissemination; metastasis to the oral region may affect soft tissues and jawbones, accounting for approximately 1% of all oral malignant neoplasms. The diagnosis of metastatic lesions to the oral cavity is usually challenging to clinicians and pathologists because of their complexity and rarity. We present a series of 12 metastatic neoplasms to the oral cavity that were detected previously or after the diagnosis of the primary tumor. All tumors were of epithelial origin with primary sites in the esophagus (2 cases), colon (2 cases), bladder, lungs, liver, larynx, skin, uterus, prostate, and adrenal gland, each with one case. The commonest site of the metastatic masses in the oral cavity was the gingiva, frequently presented as a vegetating, friable mass. The clinical examination and histopathologic analysis of the lesions were central to establishing the final diagnosis of the tumors. Metastatic masses to the oral cavity should always be considered as differential diagnosis of benign-looking lesions, especially in patients with previous history of a malignant disease. Biopsy is mandatory to establish an accurate diagnosis.
- 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.
- Extraordinary Case: Unique Presentation of an Aggressive Epstein-Barr Virus-Positive Mucocutaneous Ulcer(2022) MIYASHIRO, Denis; NICO, Marcello Menta S.; ANG, Patricia Lin; SIQUEIRA, Sheila Aparecida Coelho; PEREIRA, Juliana; SANCHES, Jose Antonio; LOURENCO, Silvia VanessaEpstein-Barr virus-positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus-related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.
article 8 Citação(ões) na Scopus Melanoma in Children, Adolescents, and Young Adults: A Clinical Pathological Study in a Brazilian Population(2014) SANCHEZ, Paula C. F.; NODA, Aliene Y. I.; FRANCO, Dilcilea D. G. S.; LOURENCO, Silvia V.; SANGUEZA, Martin; NETO, Cyro F.Malignant melanoma in children, adolescents, and young adults is unusual, especially before puberty. In children (age, 0-14 years), most primary lesions are thick and atypical (amelanotic, simulating pyogenic granuloma). In the population of adolescents and young adults (age, 15-39 years), melanoma is the third most common cancer, only behind lymphoma and breast cancer. Our study investigated the records of 89 patients diagnosed with cutaneous melanoma at age 0-39 years at Hospital das Cl nicas, Medical School, University of Sao Paulo between 1992 and 2002. They were divided into group A (0-14 years of age) and group B (15-39 years of age). The histopathology of all cases was reexamined. Statistical analysis of the data presented was performed, and the obtained data were compared with the literature. The frequency of melanoma in the group aged 15-39 years was higher in women, and the most affected site was the trunk. Additionally, melanomas were more frequent at an earlier age in patients with family history of melanoma (P = 0.014). Most cases were diagnosed, at histopathology, as superficial spreading melanoma. Thick nodular melanomas with Breslow values higher than 2 mm were associated with lymph node metastasis (P < 0.05). Our study revealed that melanoma in children, adolescents, and young adults may present peculiar behavior and outcome, which might reflect the genetic and yet not fully unraveled pathogenesis of this complex disease.- 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.
- 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.