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For cancer treatment, diagnostics concerning tumor type and determination of molecular markers in short TAT is critical. The fully automated, real-time PCR-based molecular diagnostic Idylla assays are well established in many laboratories for qualitative detection, short TAT and routine screening of clinically relevant oncogenic mutations. According to the manufacturer, all IVD assays are recommended for use only with FFPE tissue samples of 5-10 µM dissections with at least 10% tumor content. In this study, we tested the performance and accuracy of the IVD assays along with the gene fusion assay (RUO) with different tissue/source materials like isolated DNA/RNA, cryomaterial, etc. The study also included testing archival FFPE tissue sections dating back from 20 years and a performance check for different pan-cancer samples individually. All the assays tested with FFPE sections and gDNA/RNA input showed above 96% accuracy and sensitivity, individually with 100% specificity. The Idylla assays also performed exceptionally well on the archival FFPE tissues, and the use of assays for other solid tumors was also remarkable. The performance test and accuracy of Idylla assays showed high efficiency with certain limitations. For the use of Idylla assays, both qualitative and quantitative applicability of different tumor source materials could produce efficient results in different diagnostic settings within a short TAT.
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Neoplasias , Humanos , Análisis Mutacional de ADN/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Patología Molecular , ARN , MutaciónRESUMEN
Introduction: Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses. Case Presentation: A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with KIAA1549::BRAF fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up. Conclusion: We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.
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OBJECTIVE: The excision repair cross-complementation group 1 (ERCC1) expression is a predictor of survival after surgical treatment for several malignancies. Its overexpression has been reported as a marker of platinum resistance in lung cancer. However, the relevance of ERCC1 expression in ovarian cancer (OC) is the subject of controversy, both as a predictive parameter for platinum resistance and because of its association with poor prognosis. Therefore, we performed a retrospective study investigating ERCC1 expression and its correlation with patients' survival in OC. METHODS: We analyzed the ERCC1 protein expression using four different ERCC1 antibodies (clone 8F1) with different staining protocols. Immunohistochemistry was performed on multi-tissue microarrays (77 patients with primary serous ovarian cancer treated between 1999 and 2004; median age at diagnosis 67 years; range 32 to 88 years; 90% FIGO III+IV). In all cases cytoreductive surgery was followed by platinum-based chemotherapy. RESULTS: The Kaplan-Meier analysis revealed that the survival of patients with ERCC1-negative OCs (n=45; 62%) was significantly better (median survival 50.0 months) compared with the ERCC1-positive group (n=32; 38%; 20 months; p=0.004). Furthermore, ERCC1 expression was of prognostic relevance (p=0.002) in the case of negative expression in patients with residual tumor, where a higher survival rate was observed (median survival 30 months compared to 7.8 months in the ERCC1-positive group). CONCLUSIONS: ERCC1 protein overexpression may act as a prognostic marker for poor survival of high-grade OC even in patients operated with residual disease.
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Cistadenocarcinoma Seroso/enzimología , Proteínas de Unión al ADN/biosíntesis , Endonucleasas/biosíntesis , Neoplasias Ováricas/enzimología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Seroso/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual/enzimología , Neoplasia Residual/patología , Neoplasias Ováricas/patología , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
Two different studies demonstrated alpha-methylacyl coenzyme A racemase (AMACR) to be a highly specific marker in Barrett's neoplastic lesions. Reactive atypia was positive in 3/30 cases in these studies. We present a retrospective study of early Barrett's adenocarcinoma treated with surgery (2000-2005, n=29; M:F=5:1, median age 67 years). We analyzed the role of AMACR expression in reactive and neoplastic lesions associated with the disease of 77 different specimens (60 biopsy and 17 surgical specimens) of these patients. In our cohort, 70% of cases demonstrated infiltration of the submucosa, 38% were poorly differentiated, and/or 31% demonstrated lymph vessel infiltration. We used a multi-tissue array, with reactive and neoplastic samples for each patient to analyze the immunoreactivity of AMACR. Barrett's epithelium that was negative for dysplasia and columnar epithelial cell changes indefinite for dysplasia (n=30) did not demonstrate AMACR immunoreactivity. AMACR immunoreactivity was demonstrated in 27% (8/30) of cases of Barrett's epithelium with columnar epithelial cell changes indefinite for dysplasia. Altogether 91% of cases with low-grade dysplasia were AMACR-positive and 96% of cases with high-grade dysplasia and early Barrett's adenocarcinoma were positive for AMACR. In summary, the sensitivity of AMACR expression in low-grade dysplasia and subsequent early Barrett's adenocarcinoma was significantly higher in our study compared with previous data. This might be a new diagnostic marker for dysplasia carcinoma sequence in Barrett's low-grade neoplastic lesions. Further studies are required to investigate this point with well-defined controls having at least 5-years follow-up.
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Adenocarcinoma/enzimología , Esófago de Barrett/enzimología , Neoplasias Esofágicas/enzimología , Lesiones Precancerosas/enzimología , Racemasas y Epimerasas/metabolismo , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Esófago de Barrett/patología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/patología , Estudios Retrospectivos , Análisis de Matrices TisularesRESUMEN
In this study, a case of fibromyxoma of the proximal femur in a 59-year old woman is reported. The classification of this rare bone tumour is still a matter of debate and some investigators have suggested that these lesions represent a degenerative form of fibrous dysplasia. Some authors make a further distinction between fibromyxoma and myxoma of bone. In a review of 23 cases of fibromyxoma and five cases of myxoma, no differences in clinical, radiographic and biologic behaviour between fibromyxoma and myxoma were found. Apart from the age at diagnosis, the most important difference between fibromyxoma and myxoma was the degree of myxoid matrix. Therefore, we suggest that extragnathic myxoma is a regressive variant of extragnathic fibromyxoma and should be termed as the same entity. In contrast to monostotic fibrous dysplasia fibromyxoma / myxoma often causes pain and presents as a Lodwick IC lesion with a soft tissue mass. Therefore, fibromyxoma / myxoma should be distinguished from fibrous dysplasia because of its different clinical and radiographic features.
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Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Cuello Femoral , Fibroma/patología , Fibroma/cirugía , Biopsia con Aguja , Neoplasias Óseas/diagnóstico por imagen , Legrado/métodos , Femenino , Fibroma/diagnóstico por imagen , Estudios de Seguimiento , Articulación de la Cadera , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Persona de Mediana Edad , Procedimientos Ortopédicos/métodos , Dolor/diagnóstico , Dolor/etiología , Tomografía de Emisión de Positrones , Medición de Riesgo , Resultado del TratamientoRESUMEN
In 1942, Jaffe and Lichtenstein introduced the term aneurysmal bone cyst (ABC). Primary ABC is characterized by the presence of spongy or multi-cameral cystic tissue filled with blood. The process is benign, but it is locally destructive and has a high propensity for recurrence. In this paper, we present the third case of multiple metachronous primary ABCs as a rare variant of ABC. We describe the 10-year history of a 12-year-old boy with metachronous multiple primary ABCs at five different sites (right proximal humerus, right ulna, bilateral distal radius and right lateral clavicle). Furthermore, our patient suffered from vascular malformations, such as aortic isthmus stenosis, hypoplastic thoraco-abdominal aorta and bilateral renal artery stenosis. To date, in contrast to solitary ABC, the multiple lesions have been found more frequently in male individuals. Using interphase cytogenetics, we analyzed three of five of the patient's ABCs and one of these was also analyzed by GTG-banding. No chromosomal abnormalities were found. Significantly, we excluded the missense mutation of codon 201 in guanine nucleotide-binding protein 1 gene consistently found in McCune-Albright syndrome (MAS) and in non-MAS cases of polyostotic fibrous dysplasia of bone with or without secondary ABC.
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Quistes Óseos Aneurismáticos/patología , Vasos Sanguíneos/anomalías , Quistes Óseos Aneurismáticos/complicaciones , Quistes Óseos Aneurismáticos/genética , Huesos/lesiones , Preescolar , Clavícula/diagnóstico por imagen , Citogenética , Fracturas Óseas/etiología , Proteínas de Unión al GTP/genética , Humanos , Húmero/diagnóstico por imagen , Inmunohistoquímica , Masculino , Radiografía , Radio (Anatomía)/diagnóstico por imagen , Cúbito/diagnóstico por imagenRESUMEN
The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma.
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Neoplasias Óseas/genética , Condrosarcoma/genética , Cordoma/genética , Proteínas Fetales/genética , Proteínas de Dominio T Box/genética , Anciano , Biomarcadores de Tumor/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Condrosarcoma/patología , Cordoma/patología , Aberraciones Cromosómicas , Análisis Citogenético , Femenino , Proteínas Fetales/biosíntesis , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Dominio T Box/biosíntesisRESUMEN
BACKGROUND: Multiple activating mutations of the signal- and repair pathway, such as BRAF-, KRAS-mutations and microsatellite instabilities are involved in colorectal cancer pathogenesis. Molecular characterization of specifically locally advanced rectal cancers is scarce. Therefore the retrospective study addresses the intratumoral status of KRAS, BRAF and microsatellites loci with respect to tumor response and patients' antecedent including nicotine abusus, familial history, and health care to further molecularly identify rectal cancer patients. METHODS: The study assesses the molecular status of 50 rectal cancer samples (25 before and 25 after neoadjuvant 5-FU radiochemotherapy). KRAS and BRAF mutations were examined through two independent analytical methods (sequencing and SNaPshot) to ensure efficient mutation detection. The microsatellite analysis was conducted using a fluorescent multiplex PCR-based method. RESULTS: KRAS mutations were found in 9 of 25 (36%) rectal cancer patients and were not significantly associated with the response to therapy (P=0.577), age (P=0.249) or sex of the patient (P=0.566). No link exists between KRAS mutation status and nodal (P=0.371) or metastatic stage (P=0.216). For two patients, KRAS mutation status changed after application of neoadjuvant 5-FU radiochemotherapy. All tumor samples were diagnosed BRAF-negative. Two rectal cancer patients exhibited a MSI-H phenotype and showed no tumor response. CONCLUSIONS: So one can conclude that (I) KRAS mutations status may change after neoadjuvant 5-FU radiochemotherapy relevant for further therapeutic decisions; (II) MSI-H patients do not respond to neoadjuvant 5-FU radiochemotherapy. Further prospective studies are needed to validate these results.
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PURPOSE: The aim of this study was to evaluate the feasibility of phase 0 trials in the setting of a routine surgical procedure. Logistic considerations, tissue sampling and tissue handling, and variability of a biomarker during surgery, in here PARP, were evaluated. EXPERIMENTAL DESIGN: Patients with highly suspicious or proven diagnosis of advanced ovarian cancer, planned for debulking surgery were asked to allow sequential tumor biopsies during surgery. Biopsies were frozen immediately and PARP activity was measured subsequently. RESULTS: Baseline biopsies were obtained from eight patients after a median time of 88 minutes (minimum of 50 to maximum of 123 minutes). Second and third biopsies were obtained after a median of 60 (32-96) and 101 (79-130) minutes, respectively. Mean tumor load was 44% (5%-100%), with a cellular viability of 98% (85%-100%). Median baseline PARP activity was 1035 pg/mL (range, 429-2663 pg/mL). The observed interpatient variability at baseline was large: SD was 0.59 after natural logarithm transformation. CONCLUSIONS: Conducting phase 0 trials during surgery seems to be feasible in terms of logistic considerations. In preparation of a phase 0 trial during surgery, a feasibility study like this should be conducted to rule out major interactions of the surgical intervention with respect to the targeted biomarker.
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Neoplasias del Apéndice/cirugía , Biomarcadores de Tumor/metabolismo , Neoplasias Ováricas/cirugía , Poli(ADP-Ribosa) Polimerasas/metabolismo , Neoplasias Gástricas/cirugía , Adulto , Anciano , Neoplasias del Apéndice/metabolismo , Neoplasias del Apéndice/secundario , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Estudios Prospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/secundario , Resultado del TratamientoRESUMEN
PURPOSE: Evaluation of the influence of immunohistochemically defined breast cancer (BC) subtypes and other risk factors on the development of cerebral metastases (CM). METHODS: Exploratory analysis of a hospital-based prospective tumour registry including all patients with primary BC treated in our EUSOMA breast unit between 1998 and 2006. RESULTS: The study cohort contained 2441 patients, including 284 patients (11.6%) with triple-negative (oestrogen receptor (ER), progesterone receptor (PR) and HER2-negative) and 245 patients (10.1%) with HER2-overexpressing BC subtypes. Overall, 80 patients (3.3%) developed CM within a median follow-up period of 47 months, 19 (23.8%) of them with triple-negative and 19 (23.8%) with HER2-positive tumours. Therefore, 6.7% of all patients with triple-negative and 7.8% of patients with HER2-positive breast cancer developed CM. Multivariate analysis indicated that the highest risk for CM was triple-negative breast cancer. Further independent risk factors were: HER2-overexpression, early onset BC (age<50 years), and large tumour size (pT3/4). Among those patients developing CM, triple-negative BC showed the shortest interval between primary diagnosis and occurrence of CM with a median of 22 months, compared to 30 and 63.5 months in HER2-positive and ER+/HER2- BC, respectively. Survival after occurrence of CM did not differ among the subtypes. CONCLUSION: Patients with triple-negative or HER2-positive BC have a higher risk for CM compared with patients bearing the ER+/HER2- phenotype and develop CM earlier in the course of disease. A risk profile for CM might help adjust surveillance in high risk populations and identify patients with a need for new treatment strategies.
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Neoplasias Encefálicas/secundario , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Fenotipo , Factores de RiesgoRESUMEN
BACKGROUND: Hepatocyte growth factor (HGF) is a multipotent cytokine that is mediated by its receptor, c-MET. HGF/c-MET contributes to tumor progression in many human malignancies; however, HGF/c-MET is inversely correlated with aggressive biologic behavior in other cancers. Conversely, to the authors' knowledge, little is known regarding the significance of HGF/c-MET expression in skull base chordoma. METHODS: Using immunohistochemical techniques, the authors investigated HGF/c-MET expression in 46 primary and 25 recurrent lesions, and compared it with the expression of proteinases and cell differentiation markers, proliferative ability, and other clinicopathologic parameters. RESULTS: c-MET was found to be expressed in 70.0% of primary and 88.0% of recurrent lesions. HGF expression was scarcely detected. Higher c-MET expression was found to be correlated with younger patient age. Lesions with a higher expression of low molecular weight cytokeratin (CAM5.2) demonstrated significantly higher c-MET scores in both primary and recurrent lesions compared with those with lower CAM5.2 expression. In recurrent lesions, higher c-MET expression was found to be associated with the scores of matrix metalloproteinase (MMP)-1, MMP-2, tissue inhibitor of matrix metalloproteinase-1, and urokinase plasminogen activator (uPA); however, only uPA was found to be correlated with higher c-MET expression in primary lesions. c-MET expression did not appear to be correlated with MIB-1 labeling index. Patients with higher c-MET expression were found to have longer survival. CONCLUSIONS: In the current study, c-MET expression was a common event, and was found to be correlated with CAM5.2 expression, younger patient age, and a favorable prognosis in patients with skull base chordoma. However, HGF/c-MET paracrine signaling also may contribute to its invasive ability, especially in recurrent lesions.
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Cordoma/metabolismo , Cordoma/patología , Factor de Crecimiento de Hepatocito/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Neoplasias de la Base del Cráneo/metabolismo , Neoplasias de la Base del Cráneo/patología , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Proliferación Celular , Niño , Cordoma/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Neoplasias de la Base del Cráneo/terapiaRESUMEN
We present 2 cases of hibernoma, a rare lipomatous tumor arising from brown fat tissue. In each case, a hyperechoic mass in comparison to surrounding musculature combined with elevated vascularization was highly suggestive of a liposarcoma. As a rule, malignancy cannot be excluded safely by imaging modalities, and a preoperative biopsy should be performed. Although rare, hibernomas should be considered in the differential diagnosis of lipomatous soft-tissue tumors.