RESUMO
Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.
Assuntos
Angiomioma , Tumor Glômico , Miofibroma , Miopericitoma , Humanos , Miopericitoma/genética , Miopericitoma/patologia , Angiomioma/genética , Angiomioma/patologia , Tumor Glômico/genética , Tumor Glômico/patologia , Miofibroma/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Mutação , Receptor Notch3/genéticaRESUMO
AIMS: MUC4 is a transmembrane glycoprotein that plays a role in cell growth signalling and is expressed in various epithelial tissues. Gene expression profiling and immunohistochemical analyses revealed that MUC4 is also constantly and specifically expressed in low-grade fibromyxoid sarcomas and sclerosing epithelioid fibrosarcomas among the mesenchymal tumours, and immunohistochemical detection of MUC4 is extremely useful for their diagnoses. In our routine pathological practice, we noticed that meningiomas are also often positive for MUC4, which has not yet been reported previously, despite the extensive scrutiny of its expression in soft tissue tumours. METHODS AND RESULTS: We examined immunohistochemically the expression of MUC4, progesterone receptor (PgR) and somatostatin receptor 2A (SSTR2A) in 140 meningiomas of various histological subtypes and 123 other mesenchymal tumours, including intracranial or sinonasal tumours and peripheral nerve sheath tumours. MUC4 was expressed in 130 meningiomas (92.9%). MUC4 expression was constant and almost diffuse in meningothelial and angiomatous subtypes, whereas it was limited in 5% or fewer tumour cells or absent in 26 of 28 fibrous meningiomas. All other mesenchymal tumours examined were negative for MUC4. PgR and SSTR2A were expressed in 94 (67.1%) and 134 (95.7%) meningiomas, respectively. Five of six SSTR2A-negative meningiomas focally expressed MUC4. CONCLUSIONS: MUC4 is expressed variably but almost consistently in meningiomas, particularly in meningothelial or angiomatous subtypes. Its immunohistochemical detection is useful to distinguish meningiomas from other intracranial or head and neck mesenchymal tumours, particularly those with epithelioid features. Our study could expand a variety of MUC4-positive mesenchymal tumours.
Assuntos
Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Mucina-4/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico , Meningioma/patologia , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo , Receptores de Somatostatina/metabolismoRESUMO
Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e., lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain poorly understood. Because a conditional deletion of ß-catenin, a major transducer of the canonical Wingless/integrated (WNT) pathway, in the developing mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that inhibition of the WNT/ß-catenin signaling may be also involved in the development of fat cells within uterine leiomyoma. In the current study, which was performed to address this point, intracytoplasmic lipid droplets were detectable in cultured human leiomyoma cells by treatment with a potent tankyrase inhibitor, XAV939, which antagonizes ß-catenin, in a serum-starved culture medium without additional adipogenesis-inducing agents or supplements, and showed increasing accumulation in a time-dependent manner. In addition, the induction of fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)-recapitulating the local in vivo situation of uterine leiomyoma-in comparison to that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that were treated with XAV939 under hypoxia and serum starvation, whereas the immunohistochemical expression of desmin-a cytoskeletal protein representing smooth muscle differentiation-was downregulated, which appears in line with the switch in differentiation. The results of our study suggest that the inhibition of canonical WNT/ß-catenin signaling under the stress due to hypoxia and serum starvation can initiate adipocytic transdifferentiation or metaplasia in human uterine leiomyoma cells, which is potentially related to the development of lipoleiomyoma.
Assuntos
Transdiferenciação Celular , Via de Sinalização Wnt , Adulto , Técnicas de Cultura de Células , Feminino , Humanos , Hipóxia , Leiomioma/patologia , Pessoa de Meia-Idade , Cultura Primária de Células , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma. METHODS: Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α. RESULTS: FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001). CONCLUSION: Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma. KEY POINTS: ⢠R2* value obtained by IDEAL correlates with the overexpression of HIF-1α. ⢠R2* value obtained by IDEAL is associated with fibrotic focus. ⢠R2* quantification may be useful in predicting hypoxia of breast carcinoma.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tecido Adiposo , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Carcinoma Ductal/irrigação sanguínea , Carcinoma Ductal/patologia , Feminino , Fibrose , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Análise dos Mínimos Quadrados , Prognóstico , Estudos Retrospectivos , ÁguaRESUMO
Prominent cyst formation is an unusual feature of liposarcoma. We report here a case of dedifferentiated liposarcoma with huge cystic change without preoperative chemo- or radiation therapy. The lesion arose in the retroperitoneum juxtaposed to the right kidney of a 67-year-old woman. She underwent a surgical removal of the retroperitoneal cyst. The cystic tumor contained 1600 mL of old bloody fluid, and its wall was composed of edematous, inflamed or sclerosing fibrous tissue with fatty tissue containing abundant atypical stromal cells, which were immunohistochemically positive for MDM2 and CDK4, and demonstrated MDM2 gene amplification by fluorescence in situ hybridization. The wall was contiguous to an atypical lipomatous nodule located in the mesentery. The following surgical specimens of the right hemicolectomy and right nephrectomy revealed atypical cells infiltrating into the subserosa of the colon and the perirenal fat tissue or that in the renal sinus. This case indicates that well differentiated or dedifferentiated liposarcoma should be also considered as a differential diagnosis of perirenal cystic mass.
Assuntos
Quinase 4 Dependente de Ciclina/metabolismo , Lipoma/diagnóstico por imagem , Lipossarcoma/diagnóstico por imagem , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Neoplasias Retroperitoneais/diagnóstico por imagem , Idoso , Cistos/diagnóstico por imagem , Cistos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/patologia , Lipossarcoma/patologia , Imageamento por Ressonância Magnética , Neoplasias Retroperitoneais/patologiaRESUMO
A 61-year-old woman was referred to our hospital because of a right breast mass. A 19 mm hard mass was palpable in the A area of the right breast. A contrast-enhanced MRI showed rim enhancement at the peripheral region of the tumor, which was thought to represent the carcinoma component mainly at the periphery and the matrix component inside the tumor. A low density mass with rim enhancement at the peripheral region was observed in a contrast-enhanced CT, the same as in the MRI. Neither axillary lymph node metastasis nor distant metastasis was observed. A core needle biopsy of the tumor lead to a diagnosis of matrix-producing carcinoma (MPC). A breast-conserving mastectomy with sentinel lymph nodes biopsy was performed on the right breast MPC (T1c, N0, M0 Stage I). Histopathologically, the tumor demonstrated overt carcinoma with direct transition to a cartilaginous or osseous matrix and lacked an intervening spindle cell component. Immunohistochemistry showed estrogen receptor (ER) (-), progesterone receptor (PgR) (-), human epidermal growth factor receptor 2 (HER2) (-), and Ki67 index of 50%, so-called triple negative breast cancer. The tumor was also positive for SRY-related HMG box-9 (SOX9), which is a useful marker of chondroid differentiation in normal and neoplastic tissues. The patient lived free from recurrence for 5 years, even though her adjuvant therapy was only radiation therapy without adjuvant chemotherapy. MPC is an uncommon and relatively rare variant of metaplastic carcinoma, and the prognosis for patients with MPC is poorer than that for patients with ordinary breast cancer. Here we report a case of MPC of the breast with characteristic rim enhancement in contrast-enhanced MRI and CT. The intrinsic subtype and prognosis of MPC is controversial, and then we may need more experience with MPC cases.
Assuntos
Neoplasias da Mama/patologia , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Metaplasia , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
AIMS: The diagnosis of epithelioid haemangioendothelioma (EHE) is usually straightforward, based on characteristic histological features. However, it is sometimes difficult to differentiate EHE from a variety of other tumours with epithelioid morphology. The WW domain-containing transcription regulator 1-calmodulin-binding transcription activator 1 (WWTR1-CAMTA1) fusion gene, resulting in the overexpression of CAMTA1, is demonstrated in approximately 90% of EHEs, and the yes-associated protein 1-transcription factor E3 (YAP1-TFE3) fusion gene, associated with the strong and diffuse nuclear expression of TFE3, is present in another small subset of EHEs. The aim of our study was to examine CAMTA1 expression in EHEs and a variety of other tumours to evaluate its diagnostic utility, and to analyse TFE3 expression status in EHEs. METHODS AND RESULTS: Immunohistochemistry was performed on 16 EHEs, including five cases with CAMTA1 rearrangement and 276 non-EHE tumours. Fourteen of 16 EHEs and only one case of ductal carcinoma of the breast were positive for CAMTA1 and its expression was focal and weak in the latter (sensitivity 87.5%, specificity 99.6%). TFE3 expression was expressed focally and weakly in three (19%) EHEs (two with the CAMTA1 rearrangement). CONCLUSIONS: Nuclear CAMTA1 expression is sensitive and highly specific for EHE and can be applied to diagnostic immunohistochemistry in epithelioid tumours.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Hemangioendotelioma Epitelioide/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Transativadores/metabolismo , Adulto , Idoso , Criança , Feminino , Hemangioendotelioma Epitelioide/metabolismo , Hemangioendotelioma Epitelioide/patologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/metabolismo , Neoplasias de Tecidos Moles/patologiaRESUMO
OBJECTIVES: The aim of this study was to assess the susceptibility change in medial and lateral globus pallidus (GPm and GPl) related to age separately, using quantitative susceptibility mapping (QSM) and to determine whether QSM can depict GPm in Parkinson's disease (PD) patients. METHODS: QSM was performed in 19 PD patients and in 41 normal control (NC) subjects. First, we quantitatively analysed age-related changes in QSM value in NC for GPl and GPm by a manual region of interest (ROI) technique. Then, in PD patients and age-matched NC subjects, we evaluated the depiction of GPm on QSM images qualitatively. RESULTS: In NC, the QSM value within GPl significantly increased gradually with age (r = 0.32, p = 0.04), whereas it did not change with age in GPm. The average QSM value was significantly larger for GPl than for GPm (205 vs 191, p < 0.05). In both PD patients and age-matched NC, the depiction of GPm on QSM images was good in most cases (87 %, 33 of 38 sides in PD patients) mainly because of the differences in susceptibility between GPm and GPl. CONCLUSIONS: The QSM value in GPl increases gradually with age, which allows for the identification of GPm in elderly PD subjects.
Assuntos
Mapeamento Encefálico/métodos , Globo Pálido/patologia , Doença de Parkinson/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos ProspectivosRESUMO
BACKGROUND: Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors, however, they often remain asymptomatic and are commonly discovered on autopsy. Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma, melanoma, lung cancer, and breast cancer, whereas reports of esophageal cancer with cardiac metastasis are rare. CASE SUMMARY: The case of a 60-year-old man who complained of dysphagia is presented. Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis. Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor, multiple liver and lung metastases, and a left pleural effusion. Pathological examination of a biopsy specimen from the esophageal tumor showed spindle-shaped cells, raising suspicion of esophageal sarcoma. The disease progressed rapidly, and systemic chemotherapy was deemed necessary, however, due to his poor general condition, administration of cytotoxic agents was considered difficult. Given his high Combined Positive Score, nivolumab was administered, however, the patient soon died from the disease. The autopsy confirmed spindle cell carcinoma (SCC) of the esophagus and cardiac metastasis with similar histological features. Cancer stem cell markers, ZEB1 and TWIST, were positive in both the primary tumor and the cardiac metastasis. CONCLUSION: To the best of our knowledge, there have been no prior reports of cardiac metastasis of esophageal SCC. This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease, with the autopsy examination showing cardiac metastasis.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Estenose Esofágica , Neoplasias Cardíacas , Neoplasias Pulmonares , Melanoma , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cardíacas/diagnóstico por imagem , Miocárdio , Homeobox 1 de Ligação a E-box em Dedo de ZincoRESUMO
Liposarcomas are a representative group of soft tissue sarcomas with variably hampered adipogenesis, which is most exemplified by its dedifferentiated subtype. However, the factor(s) responsible for inhibiting adipocyte differentiation remains unknown. A recent gene expression profiling study identified several unique genes that were highly expressed in dedifferentiated liposarcoma, and the gene encoding calreticulin (CALR), a major Ca(2+)-buffering protein that can inhibit adipocyte differentiation, was found to be overexpressed. Thus, we investigated the expression of calreticulin in 45 cases of liposarcomas, including 15 dedifferentiated tumors, at both the protein and mRNA levels. Immunohistochemically, calreticulin was consistently expressed in the dedifferentiated areas of dedifferentiated liposarcomas and commonly observed in atypical stromal cells and/or lipoblasts in the well-differentiated areas (87%), whereas large vacuolated adipocytic cells in either the tumors or normal fat were essentially negative. These results were further supported by the findings of Western blot and quantitative RT-PCR analyses. Although abnormalities in 19p13.1-13.2 where CALR is localized were uncommon in the dedifferentiated liposarcomas examined by fluorescence in situ hybridization, expression of miR-1257, a putative microRNA that targets calreticulin, was suppressed in the dedifferentiated subtype. The down-regulation of calreticulin by small-interfering RNA could induce adipogenesis in dedifferentiated liposarcoma cells and reduce cell proliferation. Our results therefore suggest that aberrantly expressed calreticulin in dedifferentiated liposarcoma is involved in its dedifferenitation and/or tumor progression.
Assuntos
Calreticulina/metabolismo , Lipossarcoma/metabolismo , Adipócitos/patologia , Calreticulina/genética , Calreticulina/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Perfilação da Expressão Gênica/métodos , Técnicas de Silenciamento de Genes/métodos , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiologia , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Células Tumorais CultivadasRESUMO
Lipoblastoma is a distinct benign fatty tumor composed of adipocytes, lipoblasts, and primitive mesenchymal cells with a myxoid stroma. Lipoblastoma harbors characteristic fusion genes involving the PLAG1, resulting in aberrant expression of PLAG1. However, the nature of the primitive mesenchymal cells remains obscure. In our routine pathology practice, we noticed desmin-positive spindle mesenchymal cells in lipoblastomas, which is a hitherto poorly described phenomenon. Thus, we examined the expression of several myogenic markers including desmin in a variety of 95 mesenchymal tumors with fatty elements. Fourteen of the 15 lipoblastomas examined contained desmin-positive spindle cells, which also showed nuclear expression of PLAG1, whereas α-smooth muscle actin, muscle specific actin, h-caldesmon, and myogenin were negative. Some spindle cells in subsets of atypical lipomatous tumors/well differentiated liposarcomas (6/20), dedifferentiated liposarcomas (11/31) and pleomorphic liposarcomas (2/10) were positive for actins and/or desmin, supporting focal myofibroblastic or smooth muscle differentiation. The other tumors, including 11 myxoid/round cell liposarcomas, four spindle cell lipomas, and four lipofibromatoses, were negative for all of the myogenic markers assessed. The almost consistent desmin expression in spindle mesenchymal cells suggests a potential diagnostic utility of this marker and myofibroblastic phenotype of fractions in lipoblastoma cells.
Assuntos
Biomarcadores Tumorais/metabolismo , Desmina/metabolismo , Lipoblastoma/metabolismo , Lipoblastoma/patologia , Biomarcadores Tumorais/análise , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Desmina/análise , Feminino , Humanos , Imuno-Histoquímica , Lactente , Lipoblastoma/genética , Masculino , Mesoderma/metabolismo , Mesoderma/patologia , FenótipoRESUMO
Sclerosing mucoepidermoid carcinoma with eosinophilia (SMCE) of the salivary gland is a rare variant of mucoepidermoid carcinoma. We report a case of SMCE in the right submandibular gland of a 79-year-old man. Fine needle aspiration cytology revealed cohesive clusters of atypical squamous epithelial cells admixed with cells containing intracytoplasmic mucin and eosinophils. Histologically, the tumor was composed of epithelial nests with keratinizing cells occasionally present at the center, as well as peripherally located atypical basaloid cells, and some mucin-containing cells embedded in a fibrosclerotic stroma, which were accompanied by a prominent lymphoplasmacytic and eosinophilic infiltrate. Inflammatory infiltrate and stromal fibrosclerosis also were seen in the non-neoplastic salivary gland tissue adjacent to the tumor. Immunohistochemically, many plasma cells were IgG4-positive. The postoperative serum IgG4 level was elevated. Our reverse transcription-polymerase chain reaction using formalin-fixed, paraffin-embedded tumor tissue failed to detect any fusion-gene transcripts which are specifically identified in ordinary mucoepidermoid carcinoma. The findings of the present case suggest that this rare type of salivary gland carcinoma may be associated with a chronic inflammatory condition such as IgG4-related sclerosing disease. Only 23 cases of sclerosing mucoepidermoid carcinoma with or without eosinophilic infiltratie have been reported to date in such an anatomical location.
Assuntos
Carcinoma Mucoepidermoide/patologia , Eosinofilia/patologia , Neoplasias da Glândula Submandibular/patologia , Idoso , Carcinoma Mucoepidermoide/imunologia , Carcinoma Mucoepidermoide/metabolismo , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/metabolismo , Masculino , Esclerose , Neoplasias da Glândula Submandibular/imunologia , Neoplasias da Glândula Submandibular/metabolismoRESUMO
Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P<0.05) and the poor survival of the patients (P<0.001 and P=0.001, respectively). Our data suggest that an overexpression of miRNA-21 is, therefore, associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of the expression of tumor suppressors, PDCD4 and TIMP3, thus resulting in tumor progression and the adverse clinical course of pancreatic ductal adenocarcinoma.
Assuntos
Proteínas Reguladoras de Apoptose/análise , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/química , Carcinoma Ductal Pancreático/genética , MicroRNAs/análise , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/genética , Proteínas de Ligação a RNA/análise , Inibidor Tecidual de Metaloproteinase-3/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
PLAG1, a proto-oncogene activated in several types of tumors including pleomorphic adenoma of the salivary gland and lipoblastoma, is usually overexpressed because of chromosomal aberrations resulting in fusion genes. Myoepithelial tumors in soft tissue are morphologically similar to pleomorphic adenoma, but the genetic profiles of these tumors have not been fully examined. In the present study, we immunohistochemically evaluated the expression of PLAG1 in a series of 243 mesenchymal tumors. We determined that 14 tumors, including eight of 10 lipoblastomas, two of seven gastrointestinal stromal tumors, one of two angiomyofibroblastomas, one of five synovial sarcomas, one of seven leiomyomas and one of 12 myxofibrosarcomas were positive for PLAG1, whereas all seven soft tissue myoepitheliomas were PLAG1 negative. We examined two soft tissue myoepitheliomas, whose paraffin blocks were available, for fusion gene transcripts involving PLAG1 or HMGA2 specific for pleomorphic adenoma by a reverse transcription-polymerase chain reaction assay, and no fusion transcripts were detected. Our results suggest that soft tissue myoepithelioma may be a pathogenetically distinct tumor entity from pleomorphic adenoma based on the absence of PLAG1 overexpression and characteristic fusion genes. On the other hand, PLAG1 immunohistochemistry is useful for distinguishing lipoblastoma from other lipomatous tumors including liposarcoma.
Assuntos
Adenoma Pleomorfo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Mioepitelioma/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/patologia , Proteínas de Ligação a DNA/genética , Fusão Gênica/genética , Proteína HMGA2/genética , Humanos , Imuno-Histoquímica , Mioepitelioma/genética , Mioepitelioma/patologia , Proto-Oncogene Mas , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/metabolismo , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologiaRESUMO
MicroRNAs (miRNAs) are noncoding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b, and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma.
Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Sarcoma Sinovial/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Sarcoma Sinovial/genética , Regulação para CimaRESUMO
Intracystic papillary neoplasm (ICPN) of the gallbladder is a rare clinicopathological entity with a wide range of malignant potentials. Here, we report a case of mucin-producing gallbladder carcinoma possibly derived from ICPN. A 78-year-old female patient was referred to our hospital for examination of jaundice. Abdominal CT showed dilated biliary trees and a contrast-enhanced large polypoid mass in the gallbladder. Duodenoscopy showed a large amount of mucin extravasating from the ampulla of Vater. Bile cytology showed no evidence of malignancy. Under the diagnosis of mucin-producing gallbladder tumor, we performed laparoscopic cholecystectomy. Macroscopically, there was a large papillary tumor throughout the entire gallbladder mucosa. Pathological examinations showed a gallbladder adenocarcinoma localized to the mucosa in association with ICPN. Immunohistochemical analysis of the tumor revealed positive staining for MUC2 and MUC5AC but negative for MUC1 and MUC6, suggestive of the intestinal type.
Assuntos
Adenocarcinoma Papilar , Adenocarcinoma , Ampola Hepatopancreática , Neoplasias da Vesícula Biliar , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma Papilar/complicações , Adenocarcinoma Papilar/diagnóstico , Adenocarcinoma Papilar/cirurgia , Idoso , Biomarcadores Tumorais , Feminino , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Mucina-5AC , Mucina-2 , Mucina-6 , MucinasRESUMO
Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.
Assuntos
Adipócitos/química , Biomarcadores Tumorais/análise , Núcleo Celular/química , Lipoma/química , Proteínas Proto-Oncogênicas c-mdm2/análise , Adipócitos/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Núcleo Celular/patologia , Quinase 4 Dependente de Ciclina/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipoma/genética , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/análise , Peptidase 7 Específica de Ubiquitina/análise , Proteína Desacopladora 1/análise , Adulto JovemRESUMO
Vascular leiomyosarcoma (LMS) is the least frequent type of soft-tissue LMS and has not been fully evaluated immunohistochemically. The aim of the present study was therefore to examine four cases of vascular LMS, paying special attention to the immunohistochemical expression of smooth muscle markers. All the patients were female; two tumors were located within the inferior vena cava, one within the saphenous vein, and one within the external iliac vein. All the tumors displayed well-moderately differentiated smooth muscle morphology. On immunohistochemistry all four vascular LMS were diffusely and strongly reactive to actins, calponin, and h-caldesmon, whereas desmin was diffusely stained in one tumor, only focally positive in two, and negative in one. The walls of the blood vessels contiguous to the tumors contained desmin- and h-caldesmon-positive smooth muscle cells in two cases. In contrast, among 43 non-vascular LMS (20 well-moderately differentiated and 23 poorly differentiated or other types), 38 were variably positive for desmin, whereas 21 were negative for h-caldesmon. These findings suggest that the vascular LMS displays a distinctive phenotype of smooth muscle differentiation according to histopathogenesis.
Assuntos
Leiomiossarcoma/patologia , Músculo Liso/patologia , Neoplasias Vasculares/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Desmina/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Leiomiossarcoma/metabolismo , Pessoa de Meia-Idade , Músculo Liso/metabolismo , Neoplasias Vasculares/metabolismoRESUMO
Extraspinal ependymoma is a rare tumor, occurring most commonly in the sacrococcygeal region, and only a small number of cases have been reported to arise in the uterine ligament. Herein is reported a case of extraspinal ependymoma arising in the broad ligament of a 27-year-old woman. The lesion was 14 cm in diameter with an intra-abdominal implant in the omentum. On cut section the tumor was found to be solid, and demonstrated hemorrhaging, necrosis, myxoid foci, and central cystic spaces. Microscopically the tumor was composed of a proliferation of short spindle or polygonal cells arranged in short fascicles or in a solid sheet-like fashion with occasional perivascular pseudorosettes, together with myxoid areas and variable histological architectures exhibiting cribriform, pseudopapillary, and variable-sized cystic patterns. On immunohistochemistry most tumor cells were positively reactive to glial fibrillary acidic protein (GFAP), CD99, estrogen receptor, and progesterone receptor. The patient has remained disease-free for 6 months after the adjuvant chemoradiotherapy. Extraspinal ependymoma should be considered as a differential diagnosis when examining unusual intrapelvic tumors, especially in young female patients. The identification of characteristic histological features such as perivascular pseudorosettes and immunohistochemical expression of GFAP are helpful for confirming the diagnosis.
Assuntos
Ligamento Largo/patologia , Ependimoma/patologia , Neoplasias dos Genitais Femininos/patologia , Adulto , Ligamento Largo/cirurgia , Proliferação de Células , Quimioterapia Adjuvante , Ependimoma/terapia , Feminino , Neoplasias dos Genitais Femininos/terapia , Humanos , Histerectomia , Imuno-Histoquímica , Ovariectomia , Radioterapia Adjuvante , Resultado do TratamentoRESUMO
BACKGROUND: Metastasis of renal cell carcinoma (RCC) to the gallbladder is rare, and its clinicopathological feature remains poorly understood. We here present two cases of gallbladder metastasis from RCC presenting as a hypervascular polypoid lesion. CASE PRESENTATION: The first case was a 73-year-old man who had undergone right nephrectomy for clear cell RCC. Imaging studies detected a hypervascular polypoid lesion in the gallbladder 6 years after nephrectomy. Laparoscopic cholecystectomy was done. The pathological findings of the polypoid lesion showed proliferation of clear cells in the submucosal layer. Immunohistochemically, the tumor was positive for carbonic anhydrase 9 (CA9) but negative for cytokeratin 7 (CK7), suggestive of metastatic RCC. The second case was a 43-year-old man who had undergone right nephrectomy for clear cell RCC. Imaging studies revealed a hypervascular polypoid lesion of 20 mm in diameter in the gallbladder 1 year after nephrectomy. The patient underwent expanded cholecystectomy and extra-hepatic bile duct resection with lymphadenectomy. Microscopically, the polypoid lesion of the gallbladder was composed of clear cells in the submucosal layer. Immunohistochemical analysis showed positive staining for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA) but negative staining for CK7, leading to the diagnosis of metastatic RCC. CONCLUSIONS: Gallbladder metastasis from RCC is rare but should be considered when a hypervascular polypoid lesion in the gallbladder is detected during the follow-up period after RCC treatment.