RESUMO
Sclerosing rhabdomyosarcoma (SRMS) is an infrequent variant of rhabdomyosarcoma characterized by extensive intercellular hyaline fibrosis. We report the case of a 37 year-old male with a 9 x 6 cm SRMS on the right elbow. Histologically, the tumor showed an abundant extracellular hyaline matrix with extratumoral vascular emboli and microscopic foci of fusocellular embryonal rhabdomyosarcoma (FRMS) separated by a fibrotic band from the sclerosing areas. One year later the patient presented with a right intratesticular tumor of 1.2 x 0.8 cm, which was reported as pure FRMS. Immunohistochemically, SRMS was positive only for MyoD1 and Vimentin and negative for Myogenin and Desmin. Both the elbow emboli with the extratumoral foci of FRMS and the intratesticular tumor were positive for Myogenin, MyoD1, Vimentin and Desmin. Using fluorescent in situ hybridization (FISH), the SRMS and the FRMS tumor cells of the elbow and the FRMS tumor cells of the testis were found to be negative for FOXO1A translocation in chromosome 13. PCR chimeric transcriptional products PAX3-FKHR and PAX7-FKHR were not found. Six months following testicular resection, the patient died of multiple metastases in the mediastinum, lung and right thigh.
Assuntos
Rabdomiossarcoma Embrionário/secundário , Neoplasias de Tecidos Moles/patologia , Neoplasias Testiculares/secundário , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Cromossomos Humanos Par 13 , Cotovelo , Evolução Fatal , Fibrose , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Orquiectomia , Rabdomiossarcoma Embrionário/química , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/cirurgia , Esclerose , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/cirurgia , Neoplasias Testiculares/química , Neoplasias Testiculares/genética , Neoplasias Testiculares/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Translocação Genética , Resultado do Tratamento , Imagem Corporal TotalRESUMO
BACKGROUND: Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation. METHODS: We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line. RESULTS: The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation. CONCLUSIONS: These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas de Transporte/genética , Neoplasias Esofágicas/genética , Proteínas dos Microfilamentos/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/metabolismo , Inibidores de Caspase , Caspases/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Colágeno/metabolismo , Inibidores de Cisteína Proteinase/farmacologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas dos Microfilamentos/metabolismo , Fatores de Tempo , Transfecção , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
To elucidate the possible involvement of gankyrin in ESCC progression and the effect of its down-regulation in ESCC, we investigated the expression of gankyrin in ESCC tissues comparing it with the corresponding normal esophageal epithelia and tested a short-hairpin RNA (shRNA) expression vector for gankyrin in ESCC cell lines. Gankyrin protein expression in 11 ESCC cell lines (KYSE series) was examined by RT-PCR and western blot. The expression of gankyrin mRNA in 30 ESCC tissues was compared with the corresponding normal epithelia by Real-time PCR. Expression of gankyrin protein was immunohistochemically analyzed in the ESCC of 103 patients. A gankyrin-shRNA vector was stably transfected into KYSE 170 cells to assess the role of gankyrin in cell motility, invasion and proliferation in vitro and tumor formation in vivo. Gankyrin expression increased in all 11 ESCC cell lines. Real-time PCR revealed that gankyrin expression was higher in the cancerous tissue for all 30 patients. In immunohistochemistry, gankyrin overexpression was correlated with lower survival rate (p = 0.0001), extent of the primary tumor, lymph node metastasis, distant lymph node metastasis and stage (p = 0.0072, p = 0.0004, p = 0.0172 and p = 0.0002, respectively). A shRNA vector against gankyrin repressed growth, cell motility, invasiveness in vitro and tumor formation in vivo. Gankyrin overexpression is associated with poor prognosis. It may play an important role in ESCC tumor progression and could be a potentially important therapeutic gene target in ESCC.
