ABSTRACT
Multiple endocrine neoplasia type 2 is an inherited cancer syndrome characterized by tumors of thyroid and adrenal tissues. Germline mutations of the REarranged during Transfection (RET) proto-oncogene, leading to its unregulated activation, are the underlying cause of this disease. Multiple endocrine neoplasia type 2 has been a model in clinical cancer genetics, demonstrating how knowledge of the genetic basis can shape the diagnosis and treatment of the disease. Here, we discuss the nature and effects of the most common recurrent mutations of RET found in multiple endocrine neoplasia type 2. Current understanding of the molecular mechanisms of RET mutations and how they alter the structure and function of the RET protein leading to its aberrant activation, and the effects on RET localization and signaling are described.
Subject(s)
Humans , Carcinoma, Medullary/genetics , /genetics , Mutation/genetics , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/genetics , Carcinoma, Medullary/physiopathology , Germ-Line Mutation , /physiopathology , Protein Conformation , Proto-Oncogene Proteins c-ret/physiology , Thyroid Neoplasms/physiopathologyABSTRACT
OBJETIVO: Avaliar as características radiológicas do câncer de mama medular em pacientes submetidas atratamento cirúrgico no Instituto Nacional de Câncer (INCA) û Ministério da Saúde, Rio de Janeiro, RJ, correlacionando os achados com estudo histopatológico. MATERIAIS E MÉTODOS: Foi realizado estudo descritivo retrospectivo de mulheres submetidas a tratamento cirúrgico no INCA, no período de janeiro de 1997 adezembro de 2006, para identificação das pacientes com carcinoma medular e análise dos achados radiológicos.RESULTADOS: Foram identificadas 21.287 pacientes com diagnóstico de carcinoma neste período, sendo 76 pacientes com diagnóstico de carcinoma medular típico (0,357%). Nessas pacientes selecionadas, a idade média foi de 51,9 anos (32 a 81 anos). Dezenove pacientes apresentavam lesão na mamografia, sendo 17 (89,5%) nódulos e 2 assimetrias focais (10,5%). Entre as pacientes com nódulo, 15 (88,1%) apresentavam alta densidade e 2 eram isodensos (11,9%). Doze pacientes apresentavam achados ultra-sonográficos e, destas, 11 (91,6%) apresentavam nódulos hipoecóicos. Foi observada uma paciente com nóduloanecóico com áreas de degeneração cística. CONCLUSÃO: O nódulo foi o achado radiológico dominante (89,5%), dos quais 88,1% apresentaram nódulos com alta densidade e margens circunscritas. Apesar das características radiológicas de benignidade, um nódulo com alta densidade, sólido, margens circunscritas e crescimento rápido deve ser investigado para confirmar o diagnóstico.
OBJECTIVE: To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil, correlating them with histological results. MATERIALS AND METHODS: A retrospective descriptive study was developed with patients submitted to surgery at INCA, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. RESULTS: Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32û81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. CONCLUSION: Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fastgrowing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis.