RESUMO
BACKGROUND: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. METHODS: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. RESULTS: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. CONCLUSION: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.
Assuntos
Alelos , Arginina/genética , Neoplasias da Mama/genética , Códon/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína Supressora de Tumor p53/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Hipóxia/fisiopatologia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prolina/genética , Transfecção , Regulação para CimaRESUMO
Parosteal lipoma is a usually indolent, rare benign tumor, characterized by clinicopathological findings similar to those of the commonly occurring subcutaneous lipoma, except for its intimate relationship with the connective tissue of the subjacent periosteal region. Parosteal lipoma commonly affects the diaphysis of long bones of the upper and lower limbs. We report an exceedingly rare case of parosteal lipoma of the rib, which presented in a 59-year-old man experiencing previous multiple traumas in this site.
Assuntos
Neoplasias Ósseas/patologia , Lipoma/patologia , Periósteo/patologia , Costelas/patologia , Neoplasias Ósseas/diagnóstico por imagem , Cartilagem/patologia , Transformação Celular Neoplásica , Humanos , Lipoma/diagnóstico por imagem , Masculino , Metaplasia , Pessoa de Meia-Idade , Periósteo/diagnóstico por imagem , Radiografia , Costelas/diagnóstico por imagem , Costelas/lesões , CicatrizaçãoRESUMO
A pregnancy luteoma (PL) was incidentally found at a term cesarean section in a 27-year-old black woman without any endocrine abnormality. The lesion involved only the left ovary; it had a nodular and focal pseudoalveolar growth pattern and was associated with areas of tubular sertoliform component, consistent with granulosa cell proliferation. Immunohistochemistry revealed a diffuse positivity to Inhibin A, CD99, cytokeratin and vimentin. The ultrastructure was typical of steroid-producing cells. PL is a tumor-like lesion arising in pregnant women and often misdiagnosed as a neoplastic lesion; awareness of this rare entity and its differential diagnoses may avoid unnecessary surgery in young patients.
