32 results on '"Vaněček, T."'
Search Results
2. Plicní adenokarcinom se vzácnou EGFR mutací i nečastou rezistencí k léčbě.
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Svatoň, M., Vaněček, T., Mukenšnabl, P., Baxa, J., and Vodička, J.
- Abstract
Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2022
3. Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women
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Králíčková, M., Ulčová-Gallová, Z., Šíma, R., Vaněček, T., Šíma, P., Křižan, J., Suchá, R., Uher, P., Hes, O., Novotný, Z., Rokyta, Z., and Větvička, V.
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- 2007
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4. Molekulární klasifikace endometriálních karcinomů převedená do praxe.
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Presl, J., Vaněček, T., Michal, M., Bouda, J., Kosťun, J., Vlasák, P., and Stráník, P.
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- 2021
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5. Sur l'Inversion Generale
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Vanecek, T. S.
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- 1882
6. Úspěšná léčba českého pacienta s plicním adenokarcinomem s BRAF V600E mutací dabrafenibem plus trametinibem.
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Svatoň, M., Pešek, M., Krákorová, G., Vaněček, T., and Baxa, J.
- Abstract
Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2021
7. 22P Next generation sequencing-based molecular profiling of lung carcinoma: A routine care experience
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Polivka, J., Pesek, M., Svaton, M., Vanecek, T., Mukensnabl, P., and Ptakova, N.
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- 2020
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8. 111 - Comparative study of TERT gene mutation analysis on voided liquid based urine cytology and paraffin embedded tumorous tissue
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Pitra, T., Pivovarcikova, K., Vanecek, T., Alaghehbandan, R., Gomolcakova, B., Ondic, O., Peckova, K., Rotterova, P., Hora, M., Michal, M., and Hes, O.
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- 2016
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9. Nový krevní test bio markeru SEPT9 a screening kolorektálního karcinomu.
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Beneš, Z., Šedivcová, M., Antoš, Z., Kohout, P., Puškárová, G., Černík, M., Rozmahel, M., Shánělová, M., Dolina, J., Hep, A., Trubač, M., Stehlík, J., Vaněček, T., Michal, M., Šimša, J., and Kala, Z.
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- 2013
10. The Leukemia inhibitory factor gene mutations in the population of infertile women: The heterozygote transition G to A on the position 3400 does not affect the outcome of the infertility treatment | Mutace v genu pro leukemický inhibiční faktor v populaci neplodných žen: Heterozygotní bodová záměna G za A na pozici 3400 neovlivǒuje úspěšnostléčby
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Kralickova, M., Šíma, R., Martínek, P., Vaněček, T., Ulčová-Gallová, Z., Šíma, P., Křižan, J., Kališ, V., Štěpán Jr., Štěpan, J., Rokyta, Z., Petr Uher, and Hes, O.
11. Discovery of Novel TULP4/ACTN4/EWSR1/ACTB::MYB and ESRRG::DNM3 Fusions Expands Molecular Landscape of Adenoid Cystic Carcinoma Beyond Fusions Between MYB/MYBL1 and NFIB Genes.
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Skálová A, Klubíčková N, Bradová M, Agaimy A, Rupp NJ, Damjanov I, Kolnikova G, Martínek P, Šteiner P, Grossmann P, Vaněček T, Michal M, and Leivo I
- Abstract
Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and occurs in all major and minor salivary gland and seromucous gland sites. AdCCs of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost consistent presence of fusion genes MYB::NFIB, or less commonly MYBL1::NFIB. We collected a cohort of 95 cases of AdCC, which were largely characterized by canonical fusions MYB::NFIB (49 cases) or MYBL1::NFIB (9 cases). In additional 11 cases of AdCC, rearrangements in MYB or NFIB genes were detected by FISH. In addition, NGS revealed novel noncanonical fusion transcripts EWSR1::MYB; ACTB::MYB; ESRRG::DNM3, MYB::TULP4, and ACTN4::MYB, each of them in 1 case. The tumors that showed noncanonical fusions had features of metatypical AdCC with a diverse architecture, lobulated multinodular growth pattern, and hypercellular peripheral palisading of nuclei (2 cases), tubular hypereosinophilia (2 cases), and pale eosinophilic to vacuolated (bubbly) cytoplasm (3 cases). Our study documented 3 cases of AdCC of salivary glands harboring novel gene fusions TULP4::MYB, ACTN4::MYB, and ACTB::MYB, in 1 case each, which have not been described before. A rare EWSR1::MYB fusion was detected in 1 case. Moreover, 1 case of sinonasal metatypical AdCC showed EWSR1 rearrangement detected by FISH. Also, 1 case with an ESRRG::DNM3 fusion of unknown significance is described in this study. These discoveries illustrate how broad molecular profiling will expand understanding of changes in known entities., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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12. SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma.
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Skálová A, Taheri T, Bradová M, Vaněček T, Franchi A, Slouka D, Kostlivý T, de Rezende G, Michálek J, Klubíčková N, Ptáková N, Nemcová A, Michal M, Agaimy A, and Leivo I
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- Humans, Middle Aged, Male, Female, Aged, Adult, Biomarkers, Tumor genetics, DNA-Binding Proteins genetics, DNA-Binding Proteins deficiency, In Situ Hybridization, Fluorescence, Diagnosis, Differential, Aged, 80 and over, High-Throughput Nucleotide Sequencing, Neoplasm Grading, SMARCB1 Protein deficiency, SMARCB1 Protein genetics, Adenocarcinoma genetics, Adenocarcinoma pathology, Transcription Factors genetics, Transcription Factors deficiency, Myoepithelioma genetics, Myoepithelioma pathology, Paranasal Sinus Neoplasms genetics, Paranasal Sinus Neoplasms pathology, Mutation
- Abstract
SMARCB1-deficient sinonasal adenocarcinoma is a rare variant of SWI/SNF-deficient malignancies with SMARCB1 loss and adenocarcinoma features. More than 200 high-grade epithelial sinonasal malignancies were retrieved. A total of 14 cases exhibited complete SMARCB1 (INI1) loss and glandular differentiation. SMARCA2 and SMARCA4 were normal, except for one case with a loss of SMARCA2. Next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH) revealed an alteration in the SMARCB1 gene in 9/13 cases, while 2/13 were negative. Two tumors harbored SMARCB1 mutations in c.157C > T p.(Arg53Ter) and c.842G > A p.(Trp281Ter). One harbored ARID1B mutations in c.1469G > A p.(Trp490Ter) and MGA c.3724C > T p.(Arg1242Ter). Seven tumors had a SMARCB1 deletion. One carried an ESR1 mutation in c.644-2A > T, and another carried a POLE mutation in c.352_374del p.(Ser118GlyfsTer78). One case had a PAX3 mutation in c.44del p.(Gly15AlafsTer95). Histomorphology of SMARCB1-deficient adenocarcinoma was oncocytoid/rhabdoid and glandular, solid, or trabecular in 9/14 cases. Two had basaloid/blue cytoplasm and one showed focal signet ring cells. Yolk sac tumor-like differentiation with Schiller-Duval-like bodies was seen in 6/14 cases, with 2 cases showing exclusively reticular-microcystic yolk sac pattern. Follow-up of a maximum of 26 months (median 10 months) was available for 8/14 patients. Distant metastasis to the lung, liver, mediastinum, bone, and/or retroperitoneum was seen in 4/8 cases. Locoregional failure was seen in 75% of patients, with 6/8 local recurrences and 3 cervical lymph node metastases. At the last follow-up, 5 of 8 (62%) patients had died of their disease 2 to 20 months after diagnosis (median 8.2 months), and 3 were alive with the disease. The original diagnosis was usually high-grade non-intestinal-type adenocarcinoma or high-grade myoepithelial carcinoma. A correct diagnosis of these aggressive tumors could lead to improved targeted therapies with potentially better overall disease-specific survival., (© 2023. The Author(s).)
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- 2024
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13. Nasal and sinonasal tumors formed by atypical adenomatous lesions arising in respiratory epithelial adenomatoid hamartoma/seromucinous hamartoma.
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Michal M, Skálová A, Hyrcza M, Laco J, Vaněček T, Rupp NJ, Michal M, Michalová K, Agaimy A, and Bradová M
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- Humans, Male, Female, Middle Aged, Aged, Adult, Nose Neoplasms pathology, Nose Neoplasms genetics, Mutation, Adenoma pathology, Adenoma genetics, Paranasal Sinus Neoplasms pathology, Paranasal Sinus Neoplasms genetics, Respiratory Mucosa pathology, Aged, 80 and over, Hamartoma pathology, Hamartoma genetics
- Abstract
Two benign adenomatous lesions are commonly recognized within the sinonasal tract, namely respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SH). We present 10 hitherto unrecognized benign polypoid nasal and sinonasal tumoriform lesions having in average 3.6 cm in largest dimension, which are histogenetically related to SH and REAH. In addition to typical structures of REAH and SH, these lesions contained an additional characteristic and slightly atypical adenomatous component, which we termed atypical sinonasal glands arising in SH (ASGSH). ASGSH often produced deep red colored secretion with peripheral clearing similar to that seen in thyroid follicles. In contrast to SH, ASGSH was endowed by both secretory and myoepithelial layers and had mostly angulated shapes with snout-like protrusions into the lumens. Both layers were formed by an irregular, disorganized, and often incomplete cell lining, which had slightly atypical cytological features without mitoses. In 3 cases, ASGSHs revealed sebaceous differentiation, and in 3 cases the stroma produced a well-differentiated cartilage. Neoplastic nature of ASGSH was supported by finding of various mutations as revealed by next generation sequencing in five cases. In two cases each, we found identical mutations in BRAF gene (Val600Glu), and RET gene (Arg912Trp), respectively and in one case FAT1 gene alteration (Pro1665Leu)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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14. Calcifying Spindle Cell Soft Tissue Tumor With SOX10::PLAG1 Fusion: A Case Report of a Morphologically Distinctive and Potentially Novel Soft Tissue Tumor.
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Kosemehmetoglu K, Mosaieby E, Šteiner P, Vaněček T, Baranovska-Andrigo V, and Michal M
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- Humans, Female, Adult, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Calcinosis genetics, Calcinosis pathology, Calcinosis metabolism, Sarcoma genetics, Sarcoma pathology, Sarcoma metabolism, SOXE Transcription Factors genetics, SOXE Transcription Factors metabolism, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms pathology, Soft Tissue Neoplasms metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism
- Abstract
The widespread use of advanced molecular techniques has led to the identification of several tumor types with PLAG1 gene fusions some of which also affect the skin and soft tissues. Herein, we present a 38-year-old female with a subcutaneous tumor affecting her forearm, which does not seem to fit into any currently recognized entity. It was a well-circumscribed tumor measuring 6 × 4,5 × 4 cm. It had a thick capsule composed of bland spindle cells forming palisades and Verocay body-like structures within a myxocollagenous background. Scattered calcifications were dispersed throughout the lesion. No cytological atypia, mitotic activity, or necrosis were present. Targeted NGS revealed a SOX10::PLAG1 fusion and fluorescent in situ hybridization confirmed the presence of PLAG1 gene rearrangement. The neoplastic cells showed a diffuse immunohistochemical expression of S100, SOX10, and PLAG1, as well as patchy desmin and CD34 positivity. The methylation profile of this tumor did not match any other entity covered by the DKFZ sarcoma classifier and apart from the gain of chromosome 12, the copy number profile was normal. The tumor was completely excised, and the patient has been free of disease for 4 years since the excision. While more cases are needed to confirm this tumor as a distinct entity, we propose a provisional name "SOX10::PLAG1-rearranged calcifying spindle cell tumor.", (© 2024 Wiley Periodicals LLC.)
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- 2024
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15. Molecular analysis of apocrine mixed tumors and cutaneous myoepitheliomas: a comparative study confirming a continuous spectrum of one entity with near-ubiquitous PLAG1 and rare mutually exclusive HMGA2 gene rearrangements.
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Mansour B, Donati M, Pancsa T, Grossman P, Šteiner P, Vaněček T, Comová K, Michal M, and Michal M
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Myoepithelial neoplasms of the skin and soft tissue still represent a confusing and somewhat controversial field in pathology as it appears that this category includes several different entities. However, recent studies have suggested that both apocrine mixed tumors (AMT) and cutaneous myoepitheliomas (CM) harbor identical chromosomal rearrangements involving the PLAG1 gene and hence may represent a morphological spectrum. The aim of the present study was to share our institutional experience with these tumors and specifically focus on studying their immunohistochemical and molecular features to further assess their relatedness. Eleven cases of AMT and 7 cases of CM were collected and analyzed using immunohistochemistry (IHC), PLAG1 FISH, and Archer FusionPlex assay. There were 14 male and 4 female patients with ages ranging from 26 to 85 years (median 55.8 years, mean 58.5 years). AMTs were mainly located in the head and neck (n = 10), while CMs were mainly located in the acral sites (n = 5). PLAG1 IHC was diffusely strongly positive in 14/17 (82%) cases, whereas a single case of AMT diffusely expressed HMGA2. Both tumor groups showed PLAG1 gene fusions which were detected in 6/13 analyzable samples (AMT, n = 4 and CM, n = 2), and included TRPS1::PLAG1 (n = 3), NDRG1::PLAG1 (n = 1), CTNNB1::PLAG1 (n = 1) and a novel PXDNL::PLAG1 fusion (n = 1). The remaining 5 cases were negative, 5 were not analyzable and the single case positive for HMGA2 by IHC revealed a potential HMGA2 gene rearrangement. The cases were further studied by FISH, with 12/17 cases showing PLAG1 gene rearrangement (AMT, n = 8 and CM, n = 4). Altogether, 14/18 cases showed PLAG1 gene rearrangement by at least one of the methods. PLAG1 immunohistochemistry had a 92% specificity and sensitivity. Our study provided additional data to suggest that AMT and CM share overlapping morphological and immunohistochemical features as well as molecular background characterized by PLAG1 gene fusions and thus represent a morphological spectrum. In addition, we identified a novel PXDNL::PLAG1 fusion and suggested that rare cases may harbor HMGA2 gene alterations which seem to be mutually exclusive with PLAG1 gene fusions. The relatedness of these tumors to salivary gland myoepithelial neoplasms and distinctness from eccrine mixed tumors and other skin and soft tissue myoepithelial neoplasms with EWSR1/FUS fusions is discussed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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16. Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.
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Klubíčková N, Dermawan JK, Mosaieby E, Martínek P, Vaněček T, Hájková V, Ptáková N, Grossmann P, Šteiner P, Švajdler M, Kinkor Z, Michalová K, Szepe P, Plank L, Hederová S, Kolenová A, Spasov NJ, Kosemehmetoglu K, Pažanin L, Špůrková Z, Baník M, Baumruk L, Meyer A, Kalmykova A, Koshyk O, Michal M, and Michal M
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- Adult, Humans, Child, Receptor, trkA genetics, Proto-Oncogene Proteins B-raf genetics, Neoplasm Recurrence, Local genetics, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis, Oncogene Proteins, Fusion genetics, Neoplasms, Connective and Soft Tissue, Fibrosarcoma genetics, Fibrosarcoma pathology, Soft Tissue Neoplasms genetics
- Abstract
Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months). Six patients were treated with targeted therapy, achieving a partial or complete response in five cases. Overall, three cases recurred and one metastasized. Eight patients were free of disease, five were alive with disease, and two patients died. All cases showed previously reported morphological patterns. Based on the cellularity and level of atypia, cases were divided into three morphological grade groups. S100 protein and CD34 were at least focally positive in 12/22 and 14/22 cases, respectively. Novel PWWP2A::RET, NUMA1::RET, ITSN1::RAF1, and CAPZA2::MET fusions, which we report herein in mesenchymal tumors for the first time, were detected by RNA sequencing. Additionally, the first uterine case with BRAF and EGFR mutations and CD34 and S100 co-expression is described. DNA sequencing performed in 13 cases uncovered very rare additional genetic aberrations. The CNV profiles showed that high-grade tumors demonstrate a significantly higher percentage of copy number gains and losses across the genome compared with low- and intermediate-grade tumors. Unsupervised clustering of the tumors' methylation profiles revealed that in 8/9 cases, the methylation profiles clustered with the IFS methylation class, irrespective of their clinicopathological or molecular features. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
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- 2024
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17. Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature.
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Bradová M, Mosaieby E, Michal M, Vaněček T, Ing SK, Grossmann P, Koshyk O, Kinkor Z, Laciok Š, Nemcová A, Straka Ľ, Farkas M, Michal M, and Švajdler M
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- Young Adult, Child, Humans, Adult, Adolescent, Middle Aged, Aged, Aged, 80 and over, In Situ Hybridization, Fluorescence, Retrospective Studies, RNA-Binding Protein EWS genetics, Gene Fusion, Biomarkers, Tumor genetics, RNA-Binding Proteins genetics, Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase genetics, DNA-Binding Proteins genetics, Transcription Factors genetics, Rhabdomyosarcoma genetics, Rhabdomyosarcoma pathology
- Abstract
Aims: Spindle-cell/sclerosing rhabdomyosarcomas (SS-RMS) are clinically and genetically heterogeneous. They include three well-defined molecular subtypes, of which those with EWSR1/FUS::TFCP2 rearrangements were described only recently. This study aimed to evaluate five new cases of SS-RMS and to perform a clinicopathological and statistical analysis of all TFCP2-rearranged SS-RMS described in the English literature to more comprehensively characterize this rare tumour type., Methods and Results: Cases were retrospectively selected and studied by immunohistochemistry, fluorescence in situ hybridization with EWSR1/FUS and TFCP2 break-apart probes, next-generation sequencing (Archer FusionPlex Sarcoma kit and TruSight RNA Pan-Cancer Panel). The PubMed database was searched for relevant peer-reviewed English reports. Five cases of SS-RMS were found. Three cases were TFCP2 rearranged SS-RMS, having FUSex6::TFCP2ex2 gene fusion in two cases and triple gene fusion EWSR1ex5::TFCP2ex2, VAX2ex2::ALKex2 and VAX2intron2::ALKex2 in one case. Two cases showed rhabdomyoblastic differentiation and spindle-round cell/sclerosing morphology, but were characterized by novel genetic fusions including EWSR1ex8::ZBTB41ex7 and PLOD2ex8::RBM6ex7, respectively. In the statistical analysis of all published cases, CDKN2A or ALK alterations, the use of standard chemotherapy and age at presentation in the range of 18-24 years were negatively correlated to overall survival., Conclusion: EWSR1/FUS::TFCP2-rearranged SS-RMS is a rare rhabdomyosarcoma subtype, affecting predominantly young adults with average age at presentation 34 years (median 29.5 years; age range 7-86 years), with a predilection for craniofacial bones, rapid clinical course with frequent bone and lung metastases, and poor prognosis (3-year overall survival rate 28%)., (© 2023 John Wiley & Sons Ltd.)
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- 2024
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18. Molecular pathology in diagnosis and prognostication of head and neck tumors.
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Skálová A, Bradová M, Michal M Jr, Mosaieby E, Klubíčková N, Vaněček T, and Leivo I
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- Humans, Salivary Glands, Immunohistochemistry, Pathologists, Pathology, Molecular, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms genetics
- Abstract
Classification of head and neck tumors has evolved in recent decades including a widespread application of molecular testing in tumors of the salivary glands, sinonasal tract, oropharynx, nasopharynx, and soft tissue. Availability of new molecular techniques allowed for the definition of multiple novel tumor types unique to head and neck sites. Moreover, the expanding spectrum of immunohistochemical markers facilitates a rapid identification of diagnostic molecular abnormalities. As such, it is currently possible for head and neck pathologists to benefit from a molecularly defined classifications, while making diagnoses that are still based largely on histopathology and immunohistochemistry. This review highlights some principal molecular alterations in head and neck neoplasms presently available to assist pathologists in the practice of diagnosis, prognostication and prediction of response to treatment., (© 2024. The Author(s).)
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- 2024
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19. Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression.
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Bradová M, Thompson LDR, Hyrcza M, Vaněček T, Grossman P, Michal M Jr, Hájková V, Taheri T, Rupp N, Suster D, Lakhani S, Nikolov DH, Žalud R, Skálová A, Michal M, and Agaimy A
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- Adult, Humans, Male, Female, In Situ Hybridization, Fluorescence, Molecular Biology, Branchioma pathology, Retinoblastoma genetics, Retinoblastoma pathology, Soft Tissue Neoplasms pathology, Retinal Neoplasms, Neoplasms, Glandular and Epithelial, Thymoma, Thymus Neoplasms
- Abstract
Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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20. Branchioma with a nested/organoid morphology: molecular profiling of a distinctive potentially misleading variant and reappraisal of potential relationship to CD34-positive/Rb1-deficient tumors of the neck.
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Baněčková M, Michal M, Vaněček T, Grossman P, Nikolov DH, Včelák R, Žalud R, Michal M, and Agaimy A
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- Aged, Female, Humans, Male, Organoids pathology, Repressor Proteins, Branchioma pathology, Retinal Neoplasms, Retinoblastoma genetics, Retinoblastoma pathology, Soft Tissue Neoplasms
- Abstract
Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS., (© 2023. The Author(s).)
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- 2023
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21. Salivary Gland Secretory Carcinoma: Clinicopathologic and Genetic Characteristics of 215 Cases and Proposal for a Grading System.
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Baněčková M, Thompson LDR, Hyrcza MD, Vaněček T, Agaimy A, Laco J, Simpson RHW, Di Palma S, Stevens TM, Brcic L, Etebarian A, Dimnik K, Majewska H, Stárek I, O'Regan E, Salviato T, Helliwell T, Horáková M, Biernat W, Onyuma T, Michal M, Leivo I, and Skalova A
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- Humans, Retrospective Studies, Ki-67 Antigen, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Neoplasm Recurrence, Local genetics, Salivary Glands metabolism, Salivary Glands pathology, Necrosis, Salivary Gland Neoplasms pathology, Mammary Analogue Secretory Carcinoma genetics
- Abstract
Salivary gland secretory carcinoma (SC), previously mammary analog SC, is a low-grade malignancy characterized by well-defined morphology and an immunohistochemical and genetic profile identical to SC of the breast. Translocation t(12;15)(p13;q25) resulting in the ETV6 :: NTRK3 gene fusion is a characteristic feature of SC along with S100 protein and mammaglobin immunopositivity. The spectrum of genetic alterations for SC continues to evolve. The aim of this retrospective study was to collect data of salivary gland SCs and to correlate their histologic, immunohistochemical, and molecular genetic data with clinical behavior and long-term follow-up. In this large retrospective study, we aimed to establish a histologic grading scheme and scoring system. A total of 215 cases of salivary gland SCs diagnosed between 1994 and 2021 were obtained from the tumor registries of the authors. Eighty cases were originally diagnosed as something other than SC, most frequently acinic cell carcinoma. Lymph node metastases were identified in 17.1% (20/117 cases with available data), with distant metastasis in 5.1% (6/117). Disease recurrence was seen in 15% (n=17/113 cases with available data). The molecular genetic profile showed ETV6 :: NTRK3 gene fusion in 95.4%, including 1 case with a dual fusion of ETV6 :: NTRK3 and MYB :: SMR3B . Less frequent fusion transcripts included ETV6 :: RET (n=12) and VIM :: RET (n=1). A 3-tiered grading scheme using 6 pathologic parameters (prevailing architecture, pleomorphism, tumor necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), and mitotic count and/or Ki-67 labeling index) was applied. Grade 1 histology was observed in 44.7% (n=96), grade 2 in 41.9% (n=90), and grade 3 in 13.5% (n=29) of cases. Compared with low-grade and intermediate-grade SC, high-grade tumors were associated with a solid architecture, more prominent hyalinization, infiltrative tumor borders, nuclear pleomorphism, presence of PNI and/or LVI, and Ki-67 proliferative index >30%. High-grade transformation, a subset of grade 2 or 3 tumors, seen in 8.8% (n=19), was defined as an abrupt transformation of conventional SC into high-grade morphology, sheet-like growth, and a tumor lacking distinctive features of SC. Both overall survival and disease-free survival (5 and 10 y) were negatively affected by tumor grade, stage, and TNM status (each P <0.0001). SC is a low-grade malignancy with predominantly solid-microcystic growth patterns, driven by a gene fusion, most commonly ETV6 :: NTRK3 . There is a low risk for local recurrence and a good overall long-term survival, with a low risk for distant metastasis but a higher risk for locoregional lymph node metastasis. The presence of tumor necrosis, hyalinization, PNI and/or LVI, and positive resection margins correlate with higher tumor grade, less favorable prognosis, and increased mortality. The statistical results allowed us to design a 3-tiered grading system for salivary SC., Competing Interests: Conflicts of Interest and Source of Funding: This study was in part supported by study grant SVV 260539 from the Ministry of Education, Czech Republic, the Cooperation Program, research area SURG, the project National Institute for Cancer Research—NICR (Programme EXCELES, ID Project No. LX22NPO5102). Funded by the European Union—Next Generation EU and the Finnish Cancer Society, Finska Läkaresällskapet, and Maritza and Reino Salonen Foundation, Finland. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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22. Mutation Profile Variability in the Primary Tumor and Multiple Pulmonary Metastases of Clear Cell Renal Cell Carcinoma. A Review of the Literature and Analysis of Four Metastatic Cases.
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Prochazkova K, Ptakova N, Alaghehbandan R, Williamson SR, Vaněček T, Vodicka J, Treska V, Rogala J, Pivovarcikova K, Michalova K, Slisarenko M, Hora M, Michal M, and Hes O
- Abstract
(1) Background: There are limited data concerning inter-tumoral and inter-metastatic heterogeneity in clear cell renal cell carcinoma (CCRCC). The aim of our study was to review published data and to examine mutation profile variability in primary and multiple pulmonary metastases (PMs) in our cohort of four patients with metastatic CCRCC. (2) Methods: Four patients were enrolled in this study. The clinical characteristics, types of surgeries, histopathologic results, immunohistochemical and genetic evaluations of corresponding primary tumor and PMs, and follow-up data were recorded. (3) Results: In our series, the most commonly mutated genes were those in the canonically dysregulated VHL pathway, which were detected in both primary tumors and corresponding metastasis. There were genetic profile differences between primary and metastatic tumors, as well as among particular metastases in one patient. (4) Conclusions: CCRCC shows heterogeneity between the primary tumor and its metastasis. Such mutational changes may be responsible for suboptimal treatment outcomes in targeted therapy settings.
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- 2021
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23. Targeted next generation sequencing of MLH1-deficient, MLH1 promoter hypermethylated, and BRAF/RAS-wild-type colorectal adenocarcinomas is effective in detecting tumors with actionable oncogenic gene fusions.
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Vaňková B, Vaněček T, Ptáková N, Hájková V, Dušek M, Michal M, Švajdler P, Daum O, Daumová M, Michal M, Mezencev R, and Švajdler M
- Subjects
- Adenocarcinoma diagnosis, Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase genetics, Colorectal Neoplasms diagnosis, DNA Methylation, Female, Genetic Testing standards, High-Throughput Nucleotide Sequencing standards, Humans, Male, Middle Aged, MutL Protein Homolog 1 genetics, Promoter Regions, Genetic, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics, Receptor Protein-Tyrosine Kinases genetics, Adenocarcinoma genetics, Colorectal Neoplasms genetics, Genetic Testing methods, High-Throughput Nucleotide Sequencing methods, MutL Protein Homolog 1 deficiency, Oncogene Proteins, Fusion genetics
- Abstract
Oncogenic gene fusions represent attractive targets for therapy of cancer. However, the frequency of actionable genomic rearrangements in colorectal cancer (CRC) is very low, and universal screening for these alterations seems to be impractical and costly. To address this problem, several large scale studies retrospectivelly showed that CRC with gene fusions are highly enriched in groups of tumors defined by MLH1 DNA mismatch repair protein deficiency (MLH1d), and hypermethylation of MLH1 promoter (MLH1ph), and/or the presence of microsatellite instability, and BRAF/KRAS wild-type status (BRAFwt/KRASwt). In this study, we used targeted next generation sequencing (NGS) to explore the occurence of potentially therapeutically targetable gene fusions in an unselected series of BRAFwt/KRASwt CRC cases that displayed MLH1d/MLH1ph. From the initially identified group of 173 MLH1d CRC cases, 141 cases (81.5%) displayed MLH1ph. BRAFwt/RASwt genotype was confirmed in 23 of 141 (~16%) of MLH1d/MLH1ph cases. Targeted NGS of these 23 cases identified oncogenic gene fusions in nine patients (39.1%; CI95: 20.5%-61.2%). Detected fusions involved NTRK (four cases), ALK (two cases), and BRAF genes (three cases). As a secondary outcome of NGS testing, we identified PIK3K-AKT-mTOR pathway alterations in two CRC cases, which displayed PIK3CA mutation. Altogether, 11 of 23 (~48%) MLH1d/MLH1ph/BRAFwt/RASwt tumors showed genetic alterations that could induce resistance to anti-EGFR therapy. Our study confirms that targeted NGS of MLH1d/MLH1ph and BRAFwt/RASwt CRCs could be a cost-effective strategy in detecting patients with potentially druggable oncogenic kinase fusions., (© 2020 Wiley Periodicals, Inc.)
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- 2020
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24. Expanding the Molecular Spectrum of Secretory Carcinoma of Salivary Glands With a Novel VIM-RET Fusion.
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Skálová A, Banečkova M, Thompson LDR, Ptáková N, Stevens TM, Brcic L, Hyrcza M, Michal M Jr, Simpson RHW, Santana T, Michal M, Vaněček T, and Leivo I
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Proto-Oncogene Proteins c-myb genetics, Salivary Proteins and Peptides genetics, Young Adult, Mammary Analogue Secretory Carcinoma genetics, Oncogene Fusion genetics, Proto-Oncogene Proteins c-ret genetics, Salivary Gland Neoplasms genetics, Vimentin genetics
- Abstract
Background: Secretory carcinoma (SC), originally described as mammary analogue SC, is a predominantly low-grade salivary gland neoplasm characterized by a recurrent t(12;15)(p13;q25) translocation, resulting in ETV6-NTRK3 gene fusion. Recently, alternative ETV6-RET, ETV6-MAML3, and ETV6-MET fusions have been found in a subset of SCs lacking the classic ETV6-NTRK3 fusion transcript, but still harboring ETV6 gene rearrangements., Design: Forty-nine cases of SC revealing typical histomorphology and immunoprofile were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). All 49 cases of SC were also tested for ETV6, RET, and NTRK3 break by fluorescence in situ hybridization and for the common ETV6-NTRK3 fusions using reverse transcription polymerase chain reaction., Results: Of the 49 cases studied, 37 (76%) occurred in the parotid gland, 7 (14%) in the submandibular gland, 2 (4%) in the minor salivary glands, and 1 (2%) each in the nasal mucosa, facial skin, and thyroid gland. SCs were diagnosed more frequently in males (27/49 cases; 55%). Patients' age at diagnosis varied from 15 to 80 years, with a mean age of 49.9 years. By molecular analysis, 40 cases (82%) presented the classic ETV6-NTRK3 fusion, whereas 9 cases (18%) revealed an alternate fusion. Of the 9 cases negative for the ETV6-NTRK3 fusion, 8 cases presented with ETV6-RET fusion. In the 1 remaining case in the parotid gland, next-generation sequencing analysis identified a novel VIM-RET fusion transcript. In addition, the analysis indicated that 1 recurrent high-grade case in the submandibular gland was positive for both ETV6-NTRK3 and MYB-SMR3B fusion transcripts., Conclusions: A novel finding in our study was the discovery of a VIM-RET fusion in 1 patient with SC of the parotid gland who could possibly benefit from RET-targeted therapy. In addition, 1 recurrent high-grade case was shown to harbor 2 different fusions, namely, ETV6-NTRK3 and MYB-SMR3B. The expanded molecular spectrum provides a novel insight into SC oncogenesis and carries important implications for molecular diagnostics, as this is the first SC-associated translocation with a non-ETV6 5' fusion partner. This finding further expands the definition of SC while carrying implications for selecting the appropriate targeted therapy.
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- 2020
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25. Vulvar Pigmented Epithelioid Melanocytoma With a Novel HTT-PKN1 Fusion: A Case Report.
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Donati M, Kastnerova L, Cempírková D, Vaněček T, Michal M, and Kazakov DV
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- Ataxia Telangiectasia Mutated Proteins genetics, Epithelioid Cells pathology, Female, Humans, Huntingtin Protein genetics, Melanocytes pathology, Mutation, Missense, Oncogene Fusion, Protein Kinase C genetics, Melanoma genetics, Melanoma pathology, Vulvar Neoplasms genetics, Vulvar Neoplasms pathology
- Abstract
Pigmented epithelioid melanocytoma is a highly pigmented, predominantly dermal melanocytic neoplasm composed by epithelioid and spindled melanocytes. It is characterized by a limited number of specific genomic alterations principally involving protein kinase A regulatory subunit alpha (PRKAR1A) and fusion of protein kinase C alpha isoform (PRKCA). However, in some of these neoplasms, no genetic aberrations have been detected. We performed genomic analysis of a nodular heavily pigmented intradermal proliferation composed of monomorphic epithelioid melanocytes with slight cytologic atypia consisting with pigmented epithelioid melanocytoma occurring on the vulva of a 24-year-old woman. A novel fusion transcript HTT-PKN1 and an ATM (Val410Ala) missense mutation were found. No other mutations including TERT-promoter hotspot mutation analysis were detected. The data expand the spectrum of molecular alterations in pigmented epithelioid melanocytoma.
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- 2020
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26. Prognostic significance of 1p36 locus deletion in adenoid cystic carcinoma of the salivary glands.
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Šteiner P, Andreasen S, Grossmann P, Hauer L, Vaněček T, Miesbauerová M, Santana T, Kiss K, Slouka D, and Skálová A
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Adenoid Cystic mortality, Carcinoma, Adenoid Cystic secondary, Carcinoma, Adenoid Cystic therapy, Disease Progression, Disease-Free Survival, Gene Fusion, Genetic Predisposition to Disease, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Male, Middle Aged, NFI Transcription Factors genetics, Neoplasm Grading, Neoplasm Recurrence, Local, Neoplasm Staging, Oncogene Proteins, Fusion genetics, Phenotype, Proportional Hazards Models, Proto-Oncogene Proteins genetics, Risk Factors, Salivary Gland Neoplasms mortality, Salivary Gland Neoplasms pathology, Salivary Gland Neoplasms therapy, Time Factors, Trans-Activators genetics, Treatment Outcome, Young Adult, Biomarkers, Tumor genetics, Carcinoma, Adenoid Cystic genetics, Chromosome Deletion, Chromosomes, Human, Pair 1, Salivary Gland Neoplasms genetics
- Abstract
Adenoid cystic carcinoma (AdCC) of the salivary glands is characterized by MYB-NFIB or MYBL1-NFIB fusion, prolonged but relentlessly progressive clinical course with frequent recurrences, and development of distant metastasis resulting in high long-term mortality. Currently, no effective therapy is available for patients with advanced non-resectable and/or metastatic disease. Complicating the clinical management of this patient group is the lack of prognostic markers. The purpose of this study is to investigate the prognostic value of 1p36 loss in patients with AdCC. The presence of 1p36 deletion and gene fusions involving the MYB, NFIB, and MYBL1 genes in a cohort of 93 salivary gland AdCCs was studied using fluorescence in situ hybridization. These results were statistically correlated with clinical data and outcome. Deletion of 1p36 in AdCC was identified in 13 of 85 analyzable cases (15.29%). MYB-NFIB fusion was detected in 57/85 (67.1%), MYBL1-NFIB fusion in 12/85 (14.1%), MYB-X fusion in 4/85 (4.7%), MYBL1-X in 4/85 (4.7%), and NFIB-X in 2/85 (2.4%) of AdCC cases. None of the 1p36-deleted samples showed MYBL1 rearrangement. Statistical analysis demonstrated a significant correlation between 1p36 deletion and advanced tumor stage and solid histology (p = 0.0061 and 0.0007, respectively). Kaplan-Meier survival curves showed statistically significant correlations between 1p36 deletion and decreased overall survival, disease-specific survival, recurrence-free interval, and recurrence-free survival, all of which were maintained in multivariate analysis. We demonstrate that 1p36 deletion can serve as an indicator of unfavorable outcome of patients with salivary gland AdCC.
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- 2018
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27. MiT translocation renal cell carcinomas: two subgroups of tumours with translocations involving 6p21 [t (6; 11)] and Xp11.2 [t (X;1 or X or 17)].
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Hora M, Urge T, Trávníček I, Ferda J, Chudáček Z, Vaněček T, Michal M, Petersson F, Kuroda N, and Hes O
- Abstract
Introduction: MiT translocation renal cell carcinomas (TRCC) predominantly occur in younger patients with only 25% of patients being over 40 years. TRCC contains two main subgroups with translocations involving 6p21 or Xp11.2. Herein we present 10 cases., Materials: Eight cases were treated at main author's institution (identified among 1653 (0.48%) cases of kidney tumours in adults). Two cases were retrieved from the Pilsen (CZ) Tumour Registry., Results: Six cases were type Xp11.2 and four 6p21; 7 female, 3 male patients; Xp11.2 4:2, 6p21 3:1. The mean age 49 years (range: 21-80), 5 patients (50%) over 40 years. The mean age of the group with Xp11.2 TRCCs was 55 (median 51) and 6p21 41 (32) years. One female with a 6p21 tumour (24 years) underwent nephrectomy at 4 months of pregnancy. Stage (UICC, 7th ed. 2009) was 5xI, 3xIII, 2xIV. The mean size of tumour was 80 (40-165) mm. The mean follow-up was 33.2 (1-92) months. In patients with 6p21 tumours, one (25%) died after 3 months due to widely metastatic disease. In patients with Xp11.2 tumours, 3 (50%) succumbed due to metastatic disease (range 1-8 months). Three patients with Xp11.2 are alive at 7, 52 and 92 months of follow-up, were diagnosed at early stage (T1a)., Conclusion: TRCCs were more common in females. Patient with 6p21 tumours were younger than those with Xp11.2. Both types have definitive malignant potential Type Xp11.2 seems to be a more aggressive neoplasm than 6p21. The case with metastatic 6p21 tumour is the 4th case described in the English literature.
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- 2014
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28. [The new blood test bio-marker SEPT9 and colorectal carcinoma screening].
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Beneš Z, Sedivcová M, Antoš Z, Kohout P, Puškárová G, Cerník M, Rozmahel M, Shánělová M, Dolina J, Hep A, Trubač M, Stehlík J, Vaněček T, Michal M, Simša J, and Kala Z
- Subjects
- Adult, Aged, Colonoscopy, Colorectal Neoplasms pathology, Early Diagnosis, Female, Humans, Male, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Retrospective Studies, Sigmoidoscopy, Biomarkers, Tumor blood, Colorectal Neoplasms blood, Colorectal Neoplasms diagnosis, Early Detection of Cancer, Septins blood
- Abstract
Due to its high incidence and mortality rates, the colorectal carcinoma represents a crucial medical issue. However, when it is detected in early stage there is high rate of successful treatment. Thats why, early stage cancer screening programmes were introduced into the clinical practice. They focus on the finding of hidden bleeding, using various laboratory techniques, sigmoidoscopy, and, primarily, colonoscopy. However, screening programmes have not yet reached the effect required. New techniques are therefore being developed, such as the detection of blood bio-markers. This group includes also methylated SEPT9 (mSEPT9) detection in blood. We applied this test on 57 patients; we divided the group into two parts. There were 33 asymptomatic individuals in the first group. In this group, we were got only one positive mSEPT9 result. The consequent colonoscopies were negative. The other group had 24 proven carcinomas. Of them, two had negative mSEPT9 results. The remaining in all 22 patients was tested mSEPT9 positive. After its efficiency is tested by further studies, this test may be used especially for patients with low compliance, as it only requires routine blood drawing.
- Published
- 2013
29. Mammary analog secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/myoepithelial markers (calponin, CD10 and p63 protein).
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Laco J, Švajdler M Jr, Andrejs J, Hrubala D, Hácová M, Vaněček T, Skálová A, and Ryška A
- Subjects
- Adult, Breast Neoplasms genetics, Breast Neoplasms metabolism, Calcium-Binding Proteins analysis, Calcium-Binding Proteins biosynthesis, Carcinoma genetics, Carcinoma metabolism, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Membrane Proteins analysis, Membrane Proteins biosynthesis, Microfilament Proteins analysis, Microfilament Proteins biosynthesis, Middle Aged, Neprilysin analysis, Neprilysin biosynthesis, Oncogene Proteins, Fusion genetics, Parotid Neoplasms genetics, Parotid Neoplasms metabolism, Reverse Transcriptase Polymerase Chain Reaction, Calponins, Biomarkers, Tumor analysis, Breast Neoplasms pathology, Carcinoma pathology, Parotid Neoplasms pathology
- Abstract
Mammary analog secretory carcinoma (MASC) of salivary glands is a recently described neoplasm with favorable outcome. We describe 2 cases of MASC occurring in a 34-year-old female and a 58-year-old male, both presenting with a swelling of upper lip and right parotid gland, measuring 15 and 20mm, respectively. Without adjuvant treatment, both patients have been free of disease for 15 months and 12 months since the operation. Microscopically, both tumors were cystic and showed tubular and cystopapillary architecture. The tumor cells had round to oval nuclei and eosinophilic cytoplasm. Presence of eosinophilic material was evident within cystic spaces. Immunohistochemically, both tumors expressed cytokeratins (CK), CK7, CK8, CK18, epithelial membrane antigen, vimentin, S-100 protein, mammaglobin, and STAT5a (signal transducer and activator of transcription 5a). Interestingly, both tumors showed variable expression of basal/myoepithelial markers. In one case, we observed diffuse expression of calponin and focal expression of p63 whereas expression of CD10 was absent. In the second case, the staining of calponin was negative, but there was focal expression of both p63 and CD10. Both neoplasms harbored the ETV6-NTRK3 fusion transcript as proved by RT-PCR. Although previously reported only rarely, we conclude that MASC may show expression of basal/myoepithelial markers., (Copyright © 2013 Elsevier GmbH. All rights reserved.)
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- 2013
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30. A distinctive translocation carcinoma of the kidney; "rosette forming," t(6;11), HMB45-positive renal tumor: a histomorphologic, immunohistochemical, ultrastructural, and molecular genetic study of 4 cases.
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Petersson F, Vaněček T, Michal M, Martignoni G, Brunelli M, Halbhuber Z, Spagnolo D, Kuroda N, Yang X, Cabrero IA, Hora M, Branžovský J, Trivunic S, Kacerovská D, Steiner P, and Hes O
- Subjects
- Adult, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 6, Female, Humans, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Loss of Heterozygosity, Male, Melanoma-Specific Antigens metabolism, Methylation, Middle Aged, Promoter Regions, Genetic, Von Hippel-Lindau Tumor Suppressor Protein genetics, Von Hippel-Lindau Tumor Suppressor Protein metabolism, gp100 Melanoma Antigen, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Melanoma-Specific Antigens genetics, Translocation, Genetic
- Abstract
To date, only a few cases of "rosette forming t(6;11), HMB45-positive renal carcinoma" have been published. In this article, we contribute further data on 4 cases of this rare entity. Patients were 3 women and 1 man with an age range of 20 to 54 years (median, 23 years). Follow-up (range, 3-5 years; median, 4 years) did not reveal any metastatic events or recurrences. All tumors were well circumscribed and mostly encapsulated with homogeneous gray to tan cut surfaces. No necrosis was seen. All tumors displayed a solid or solid/alveolar architecture and contained occasionally long and branching tubular structures composed of discohesive neoplastic cells and pseudorosettes. The presence of pseudorosettes was a constant finding, but the number of pseudorosettes varied significantly among cases. All cases displayed focal immunoreactivity for the melanocytic marker HMB45, cathepsin K, and vimentin. Melan A, tyrosinase, cytokeratins, CD10, and microphthalmia transcription factor were each positive in 3 of 4 cases. On ultrastructural examination, numerous electron-dense secretory cytoplasmic granules with some resemblance to melanosomes were identified. The pseudorosettes were composed of reduplicated basement membrane material surrounded by small lymphocyte-like neoplastic cells. Using reverse transcription polymerase chain reaction, 2 tumors were positive for the Alpha-TFEB fusion transcript. The presence of the translocation t(6;11)(Alpha-TFEB) was confirmed in 2 analyzed cases. No von Hippel-Lindau tumor suppressor gene mutation, promotor methylation or loss of heterozygosity of 3p was found. Losses of part of chromosome 1 and chromosome 22 were found in one case., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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31. Bilateral renal tumors; conventional clear cell carcinoma and contralateral t(6;11)/t(X;17)-like tumor Histomorphologic, immunohistochemical, ultrastructural and molecular genetic studies including the report of a novel mutation in the VHL gene.
- Author
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Petersson F, Michal M, Vaněček T, Hora M, Trivunic S, Halbhuber Z, and Hes O
- Subjects
- Adult, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell surgery, Chromosomes, Human, 6-12 and X, Chromosomes, Human, Pair 17, Female, Humans, Immunohistochemistry, Karyotyping, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Pregnancy, Pregnancy Complications, Neoplastic pathology, Pregnancy Complications, Neoplastic surgery, Carcinoma, Renal Cell genetics, Kidney Neoplasms genetics, Mutation, Pregnancy Complications, Neoplastic genetics, Translocation, Genetic, Von Hippel-Lindau Tumor Suppressor Protein genetics
- Abstract
A 34-year-old pregnant woman with bilateral kidney tumors 9.5 and 2.5 cm in maximum diameter is presented. The larger tumor was clear renal cell carcinoma. The smaller contralateral tumor was focally HMB45 positive and had unusual histomorphology, including features resembling clear renal cell carcinoma with features of both t(6;11)- and t(X;17)/ASPL-TFE3 carcinomas. This tumor displayed a complex karyotype. A novel germ line mutation in the VHL gene (c.439A>G/p.I147V) was also identified in this patient., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
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32. Mutational analysis (c.402C>G) of the FOXL2 gene and immunohistochemical expression of the FOXL2 protein in testicular adult type granulosa cell tumors and incompletely differentiated sex cord stromal tumors.
- Author
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Hes O, Vaněček T, Petersson F, Grossmann P, Hora M, Perez Montiel DM, Steiner P, Dvořák M, and Michal M
- Subjects
- Adolescent, Adult, Aged, Cell Differentiation, Child, Child, Preschool, DNA Mutational Analysis, Female, Forkhead Box Protein L2, Forkhead Transcription Factors genetics, Genetic Association Studies, Granulosa Cell Tumor diagnosis, Granulosa Cell Tumor pathology, Humans, Immunohistochemistry, Infant, Male, Middle Aged, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Point Mutation genetics, Sex Cord-Gonadal Stromal Tumors diagnosis, Sex Cord-Gonadal Stromal Tumors pathology, Testicular Neoplasms diagnosis, Testicular Neoplasms pathology, Forkhead Transcription Factors metabolism, Granulosa Cell Tumor genetics, Ovarian Neoplasms genetics, Sex Cord-Gonadal Stromal Tumors genetics, Testicular Neoplasms genetics
- Abstract
Background: Recently a somatic point mutation in the FOXL2 gene has been characterized in ovarian adult type of granulosa cell tumor (ATGCT) (94.6%), thecomas (12.5%), but not in juvenile type of ovarian granulosa cell tumor, other ovarian sex cord tumors and ovarian surface epithelial neoplasms. Whether this mutation is present in testicular ATGCT or incompletely differentiated sex cord stromal tumor (ISCST) is not known., Design: Four ATGCTs, 4 ISCST were immunohistochemically investigated with anti-FOXL2 and 3 ovarian ATGCTs were used as positive control., Results: Weak-to-moderate immunoreactivity was found in all tested testicular and ovarian tumors. PCR and direct sequencing were used for detection of c.402C>G of the FOXL2 gene. No mutation was found in any of the testicular ATGCTs or ISCSTs whereas all ovarian tumors showed the c.402C>G point mutation of the FOXL2 gene., Conclusions: On the basis of this small series of these rare testicular neoplasms, it seems that the c.402C>G mutation of the FOXL2 gene frequently found in adult type of ovarian GCT does not play any significant role in the development of ATGCT and ISCST.
- Published
- 2011
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