RESUMO
BACKGROUND: Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to yield α-ketoglutarate (α-KG) with production of reduced nicotinamide adenine dinucleotide (NADH). Dysfunctional IDH leads to reduced production of α-KG and NADH and increased production of 2-hydroxyglutarate, an oncometabolite. This results in increased oxidative damage and stabilization of hypoxia-inducible factor α, causing cells to be prone to tumorigenesis. METHODS: This study investigated IDH mutations in 61 Ewing sarcoma family tumors (ESFTs), using a pentose nucleic acid clamping method and direct sequencing. RESULTS: We identified four cases of ESFTs harboring IDH mutations. The number of IDH1 and IDH2 mutations was equal and the subtype of IDH mutations was variable. Clinicopathologic analysis according to IDH mutation status did not reveal significant results. CONCLUSIONS: This study is the first to report IDH mutations in ESFTs. The results indicate that ESFTs can harbor IDH mutations in previously known hot-spot regions, although their incidence is rare. Further validation with a larger case-based study would establish more reliable and significant data on prevalence rate and the biological significance of IDH mutations in ESFTs.
RESUMO
Chemokines are a family of peptide mediators that play an essential role in cellular migration and intracellular communication in tumor cells as well as immune cells. We hypothesized that the CXCL16-CXCR6 ligand-receptor system plays an important role in Ewing sarcoma (ES) family tumor (ESFT) progression. Using real-time quantitative reverse transcription-polymerase chain reaction, we investigated the mRNA expression of CXCL16, CXCR6, and ADAM 10 in various cell lines. We also investigated the expression of CXCL16, CXCR6, ADAM 10, and ADAM 17 in tissue samples from 61 ESFT patients using immunohistochemistry. The mRNA expression levels of CXCL16 and CXCR6 in the ES cell line were higher than those in the other cell lines. Immunohistochemical staining revealed that CXCL16 and CXCR6 were highly expressed in tumor cells of ESFT and showed a positive correlation between them. The expression of CXCL16 and CXCR6 was associated with the occurrence of lung metastasis. Univariate analysis revealed that CXCL16 or CXCR6 expression was associated with worse prognosis of ESFT patients. In addition, CXCL16 and CXCR6 expression was associated with shorter overall survival irrespective of other prognostic factors. Our results suggest that the CXCL16/CXCR6 axis appears to be important in the progression of ESFT, resulting in more aggressive clinical behavior. Furthermore, there may be a decrease in the overall survival in ESFT patients who have tumors that stain strongly for CXCL16 and CXCR6.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/metabolismo , Quimiocinas CXC/biossíntese , Receptores de Quimiocinas/biossíntese , Receptores Depuradores/biossíntese , Receptores Virais/biossíntese , Sarcoma de Ewing/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Quimiocina CXCL16 , Quimiocinas CXC/análise , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Humanos , Imuno-Histoquímica , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Receptores CXCR6 , Receptores de Quimiocinas/análise , Receptores Depuradores/análise , Receptores Virais/análise , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Transcriptoma , Adulto JovemRESUMO
Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is a rare variant of PTC. The term 'PTC with fibromatosis-like stroma' has been used as a synonym to describe this variant. It is characterized by extensive proliferation of fibroblasts and myofibroblasts in the tumor stroma, which occurs in up to 80% of the tumors. We herein describe a case of PTC-NFS which developed in a 49-year-old woman with the demonstration of findings of ultrasonography, fine needle aspiration cytology and histological examination of the lesion. To characterize the stromal components, we investigated the expression of several immunohistochemical markers which have been shown to be expressed differently in nodular fasciitis (NF) and fibromatosis (FM). The immunostaining results demonstrated nuclear and cytoplasmic accumulation of ß-catenin, cytoplasmic transforming growth factor-ß expression and nuclear Smad expression in the stromal cells, suggesting that the stromal cells in this case have similar molecular profiles to those of FM rather than NF.
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A uterus-like mass (ULM) is a central cavity lined by endometrial glands and stroma and surrounded by thick-walled smooth muscles. To date, 31 cases of ULM have been reported in the English literature. ULM typically presents as a single mass and is located in the pelvic cavity. We report here a very rare case of multiple extrapelvic ULMs involving the cecum, descending colon, and mesocolon. After extensive literature research, our case appears to be the first case of multiple ULMs found in extrapelvic sites and the first case of ULM in the colon. The present case suggests that ULM should be included in the differential diagnosis of colonic submucosal tumors in female patients with chronic abdominal pain or menstruation-associated symptoms.
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Solitary pancreatic metastasis of esophageal cancer is extremely rare. We report the case of a 58-year-old male admitted with esophageal cancer. Additional asymptomatic solitary hepatic and pancreatic masses were observed in the staging work-up for esophageal cancer. The hepatic mass was confirmed as a primary hepatocellular carcinoma with an ultrasound-guided needle biopsy. An esophagectomy with a distal pancreatectomy and radiofrequency ablation for hepatocellular carcinoma were performed. Histologically, the pancreatic mass was confirmed to be a metastasis from the esophageal cancer. The patient has been followed up with chemotherapy.
RESUMO
Bone formation is a rarely encountered finding during histological examination of papillary thyroid carcinoma (PTC). This study aimed to analyze clinicopathological parameters in patients with PTC showing bone formation, to document histological features of bone formation in PTC, and to investigate osteogenic proteins. Bone morphogenic protein (BMP)-9 is known as the most potent osteoinductive protein of the BMP subtypes. Recent research suggests that the activin receptor-like kinase (ALK) 1 is an essential cellular receptor that mediates BMP-9-induced osteogenic signaling. A retrospective review of tumor sections from 567 patients with a diagnosis of PTC was performed. Using immunohistochemistry and quantitative real-time polymerase chain reaction, we investigated the expression of ALK1 and BMP-9 in normal thyroid tissue and PTC samples with and without bone formation. Bone formation was found in 13% of patients with PTC. A significant association was seen between bone formation and old age. BMP-9 expression in tumors was increased compared to that in normal thyroid tissues. BMP-9 expression in tumors with bone formation was not significantly different from that in tumors without bone formation. ALK1 expression in tumors with bone formation was increased compared to that in normal thyroid tissue and tumors without bone formation. Our study suggests that upregulation of ALK1 might be an underlying molecular mechanism that explains osteogenesis in PTC.
Assuntos
Carcinoma/patologia , Ossificação Heterotópica/patologia , Neoplasias da Glândula Tireoide/patologia , Receptores de Activinas Tipo II/análise , Receptores de Activinas Tipo II/biossíntese , Adulto , Fatores Etários , Carcinoma/metabolismo , Carcinoma Papilar , Feminino , Fator 2 de Diferenciação de Crescimento/análise , Fator 2 de Diferenciação de Crescimento/biossíntese , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Ossificação Heterotópica/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismoRESUMO
Renal cell carcinoma (RCC) in autosomal dominant polycystic kidney (ADPKD) is rare. To date, 54 cases of RCC in ADPKD have been reported. Among these, only 2 cases have different histologic types of RCC. Here we describe a 45-year-old man who received radical nephrectomy for multifocal RCC with synchronous papillary and clear cell histology in ADPKD and chronic renal failure under regular hemodialysis. The case reported herein is another example of the rare pathological finding of RCC arising in a patient with ADPKD.
Assuntos
Hipergamaglobulinemia/patologia , Imunoglobulina G/análise , Gastropatias/patologia , Estômago/patologia , Biópsia , Endoscopia do Sistema Digestório , Fibrose/patologia , Mucosa Gástrica/imunologia , Humanos , Hipergamaglobulinemia/complicações , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Gastropatias/etiologiaRESUMO
AIMS: The MAPK pathway has been shown to contribute to the prognostic role and drug resistance in many cancers. In addition, the MAPK pathway was found to play a role in the aggressive behaviour of osteosarcoma (OS). We hypothesised that the expression of the MAPK pathway components may be of value in predicting the prognosis of patients with OS. METHODS: We evaluated the expression of pan-Ras, Raf-1, pMEK1/2 and pERK1/2 in 61 OS samples using immunohistochemistry and evaluated their effect on event free survival (EFS) and overall survival (OVS). RESULTS: pan-Ras, Raf-1, pMEK1/2 and pERK1/2 were found to be expressed in seven (11%), 36 (59%), 36 (59%) and 30 (49%) of 61 samples, respectively. Patients groups whose tumours expressed Raf-1, pMEK1/2 or pERK1/2 had a poorer clinical outcome than the group whose tumours did not express those antibodies. In addition, positive pMEK1/2 expression was associated with shorter EFS and OVS, irrespective of other prognostic factors. CONCLUSIONS: Our results further support the findings that aberrant expression of the MAPK pathway components may be the underlying mechanism behind OS, which results in more aggressive clinical behaviour. Furthermore, there may be a decrease in EFS and OVS in OS patients who have tumours that stain positively for pMEK.
Assuntos
Neoplasias Ósseas/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Osteossarcoma/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/mortalidade , Criança , Feminino , Humanos , MAP Quinase Quinase 1/metabolismo , MAP Quinase Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Osteossarcoma/mortalidade , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas ras/metabolismoRESUMO
AIMS: Syndecan-4 (SDC4) and fibronectin (FN), which belong to the cell adhesion molecules, have been reported to correlate with tumour growth and invasion in various carcinomas. We aimed to investigate the prognostic value of these molecules in osteosarcoma. METHODS: Using immunohistochemistry, we compared the expression of these molecules in high grade osteosarcoma to low grade central osteosarcoma, osteoid osteoma and normal bone. Further, the expression of SDC4 and FN were analysed with prognostic factors of high grade osteosarcoma. RESULTS: In high grade osteosarcoma, SDC4 was expressed in 50 of the 65 samples; of these, 32 of 65 showed strong expression profiles. FN was expressed in 46 of 65 samples, and 29 of 65 had evidence of strong expression of this molecule. SDC4 and FN expression were increased in high grade osteosarcoma as compared to other tissues. Strong SDC4 expression was associated with the occurrence of distant metastasis and a large tumour size, and strong FN expression was associated with the occurrence of distant metastasis. Strong expression of SDC4 or FN was associated with significantly shorter overall survival, respectively. CONCLUSIONS: [corrected] Increased expression of SDC4 and FN may be underlying molecular alteration of osteosarcoma which accounts for more aggressive clinical behaviour.