CCL

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001-es BibID:BIBFORM054869
035-os BibID:PMID: 25118810
Első szerző:Méhes Gábor (patológus)
Cím:Activating BRAF V600E mutation in aggressive pediatric Langerhans cell histiocytosis : demonstration by Allele-specific PCR/Direct sequencing and immunohistochemistry / Gábor Méhes, Gábor Irsai, Judit Bedekovics, Lívia Beke, Ferenc Fazakas, Tímea Rózsa, Csongor Kiss
Dátum:2014
ISSN:0147-5185
Megjegyzések:Langerhans cell histiocytosis (LCH) is a rare neoplastic disease originating from cells characterized by antigen-presenting Langerhans cell phenotype. The clinical spectrum of LCH is highly variable including localized and disseminated forms mostly occurring in children. Recently, about 60% of LCHs were reported to carry the activating BRAF mutation V600E. In our retrospective study, we evaluated the occurrence and prognostic impact of the V600E mutation in formaldehyde-fixed, paraffin-embedded samples from 15 pediatric LCH cases treated at our institution. Allele-specific polymerase chain reaction (PCR) and direct sequencing were used to demonstrate the presence of V600E mutation, and immunohistochemistry (IHC) using the mutant protein-specific VE1 antibody clone was performed to confirm mutant BRAF protein expression. Eight of 15 (53.3%) cases proved to be BRAF mutants by any of the methods applied, with a single case showing a discrepancy (PCR negative/IHC positive). Four of the BRAF-mutant cases (50.0%) showed refractory disease and progressed to death within 43 months, whereas the remaining mutant cases were stable and responded well to therapy. Wild-type BRAF cases (7/15, 46.6%) with generally comparable initial presentation were all treated successfully. In conclusion, activating V600E BRAF mutation can be frequently demonstrated in pediatric LCH by both allele-specific PCR and IHC. Unfavorable risk cases potentially also responding to BRAF-inhibitory therapy can be identified by mutation testing using archival formaldehyde-fixed, paraffin-embedded tumor samples.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:The American Journal of Surgical Pathology. - 38 : 12 (2014), p. 1644-1648. -
További szerzők:Irsai Gábor Bedekovics Judit (1986-) (orvos) Beke Lívia Fazakas Ferenc (1969-) (molekuláris biológus) Rózsa Tímea (1985-) (csecsemő- és gyermekgyógyász) Kiss Csongor (1956-) (hematológus, onkológus)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Patológia Kutatócsoport
TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
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001-es BibID:BIBFORM019456
Első szerző:Méhes Gábor (patológus)
Cím:Circulating breast cancer cells are frequently apoptotic / Gábor Méhes, Armin Witt, Ernst Kubista, Peter F. Ambros
Dátum:2001
Megjegyzések:Automatic search for cytokeratin/mucin-1 double immunofluorescence was performed to detect and characterize circulating epithelial tumor cells in patients with advanced breast cancer. The peripheral blood samples in 8 of 19 patients (42.1%) presented with cytokeratin-positive and epithelial-type mucin-positive (CK(+)/MUC1(+)) tumor cells. Detailed microscopic analysis, however, suggested that the majority of the double immunopositive cells was apoptotic according to an "inclusion type" cytokeratin staining pattern and nuclear condensation. Furthermore, apoptosis-related DNA strand breaks could be demonstrated by applying the TdT-uridine nick end labeling assay in these cells. In 3 of 8 positive samples all of the CK(+)/MUC1(+) cells displayed apoptotic features. We conclude that apoptotic cells significantly contribute to the circulating tumor cell fraction in breast cancer patients. As the predictive value of such cells for the outcome of the disease is unclear, they should be considered separately when analyzing tumor cell dissemination.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:The American Journal of Pathology. - 159 : 1 (2001), p. 17-20. -
További szerzők:Witt, Armin Kubista, Ernst Ambros, Peter F.
Internet cím:DOI
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3.

001-es BibID:BIBFORM019446
Első szerző:Méhes Gábor (patológus)
Cím:Detection of disseminated tumor cells in neuroblastoma : 3 log improvement in sensitivity by automatic immunofluorescence plus FISH (AIPF) analysis compared with classical bone marrow cytology / Gabor Mehes, Andrea Luegmayr, Rosa Kornmüller, Ingeborg M. Ambros, Ruth Ladenstein, Helmut Gadner, Peter F. Ambros
Dátum:2003
Megjegyzések:The sensitive detection of bone marrow involvement is crucial for tumor staging at diagnosis and for monitoring of the therapeutic response in the patient's follow-up. In neuroblastoma, only conventional cytomorphological techniques are presently accepted for the detection of bone marrow involvement, yet since the therapeutic consequences of the bone marrow findings may be far-reaching, the need for highly reliable detection methods has become evident. For this purpose, we developed an automatic immunofluorescence plus FISH (AIPF) device which allows the exact quantification of disseminated tumor cells and the genetic verification in critical cases. In this study, the power of the immunofluorescence technique is compared with conventional cytomorphology. 198 samples from 23 neuroblastoma patients (stages 4 and 4s) at diagnosis and during follow-up were investigated. At diagnosis, 45.6% of the samples (26 of 57) which were positive by AIPF investigation were negative by cytomorphology. During follow-up, 74.2% (49 of 66) of AIPF-positive samples showed no cytological signs of tumor cell involvement. False negative morphological results were found in up to 10% of tumor cell content. A tumor cell infiltrate below 0.1% was virtually not detectable by conventional cytomorphology. Using the sensitive immunofluorescence technique, the analysis of only two instead of four puncture sites did not lead to false negative results. Thus, the immunofluorescence technique offers an excellent tool for reliable detection and quantification of disseminated tumor cells at diagnosis and during the course of the disease
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:The American Journal of Pathology. - 163 : 2 (2003), p. 393-399. -
További szerzők:Luegmayr, Andrea Kornmüller, Rosa Ambros, Ingeborg M. Ladenstein, Ruth Gadner, Helmut Ambros, Peter F.
Internet cím:DOI
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