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المؤلفون: Pankhuri Wanjari, Jeremy P. Segal, Melissa Y. Tjota, Tatjana Antic
المصدر: Human Pathology. 115:84-95
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Vimentin, Keratin-20, Chromophobe cell, Tuberous Sclerosis Complex 1 Protein, Pathology and Forensic Medicine, 03 medical and health sciences, Tuberous sclerosis, 0302 clinical medicine, Renal cell carcinoma, Tuberous Sclerosis Complex 2 Protein, Eosinophilic, Biomarkers, Tumor, medicine, Humans, Carcinoma, Renal Cell, Retrospective Studies, biology, TOR Serine-Threonine Kinases, Keratin-7, Middle Aged, medicine.disease, Kidney Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mutation, biology.protein, Immunohistochemistry, Female, TSC1, Unclassified Renal Cell Carcinoma
الوصف: Summary Unclassified renal cell carcinoma (RCC) accounts for ∼10% of renal tumors, and the most common histologic finding in these cases is eosinophilic cytoplasm. We previously demonstrated that a subset of eosinophilic renal tumors with heterogeneous morphology and immunohistochemical (IHC) staining harbored pathogenic mutations in tuberous sclerosis complex (TSC) or mammalian target of rapamycin (MTOR) as the primary defining mutation. We identified an additional 8 cases of eosinophilic tumors with unusual morphology that were originally diagnosed as chromophobe RCC (CHRCC) or CHRCC, eosinophilic variant. As a comparison, we included four classic CHRCC cases and one CHRCC, eosinophilic variant case. Gross examination revealed solid or solid and cystic patterns. The solid areas were composed of eosinophilic tumor cells divided by congested vessels, whereas the cystic areas were lined by cytologically bland eosinophilic cells with septae containing nests, ribbons, and single eosinophilic tumor cells. The tumor cells had abundant granular eosinophilic cytoplasm with round nuclei and inconspicuous nucleoli. IHC analysis demonstrated diffuse staining for CK7 and negative staining for CK20 and vimentin. Next-generation sequencing identified pathogenic variants in three genes: TSC1, TSC2, and MTOR. They also lacked significant copy number variations in contrast to our control cases. We have demonstrated with our expanded study that cases previously diagnosed as CHRCC or CHRCC, eosinophilic variant with discordant histology and IHC staining patterns may represent a separate subtype of RCC characterized by mutations in the TSC/MTOR pathway.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b475d7debf151e10aeecbd48ae538089Test
https://doi.org/10.1016/j.humpath.2020.12.006Test -
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المصدر: Human Pathology. 91:36-42
مصطلحات موضوعية: Adult, Male, Proto-Oncogene Proteins B-raf, 0301 basic medicine, endocrine system diseases, Thyroid Nuclear Factor 1, Thyroid Transcription Factor 1, Context (language use), Follicular cell, Disease-Free Survival, Pathology and Forensic Medicine, Papillary thyroid cancer, Cohort Studies, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Thyroid Neoplasms, Iodide transport, Thyroid cancer, business.industry, Thyroid, Middle Aged, medicine.disease, 3. Good health, DNA-Binding Proteins, 030104 developmental biology, medicine.anatomical_structure, Thyroid Cancer, Papillary, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, Neoplasm Recurrence, Local, business, Transcription Factors
الوصف: Summary Function of the thyroid follicular cell depends on nuclear expression of thyroid transcription factor 1 (TTF1). Regulation of this key protein regulating iodide transport is not well known, but its loss is linked to the most lethal of thyroid malignancies. We examined TTF1 nuclear expression in the context of adverse pathological features, disease recurrence, and BRAF status in papillary thyroid carcinomas with (n = 182) and without (n = 303) nodal metastases. Overall nuclear expression level of TTF1 was strong and diffuse in approximately 73%, whereas 27% exhibited lower levels or a paucity of nuclear staining. In the same cohort, approximately 59% exhibited the BRAF mutation. On univariate analysis, low levels of TTF1 nuclear expression was linked to vascular invasion, extrathyroidal extension, and nodal metastases. Multivariate analysis indicated that low levels of TTF1 were most strongly linked to nodal metastases and vascular invasion. Interestingly, TTF1 levels were not linked to the BRAF mutation. TTF1 staining alone predicted disease recurrence, but when combined with BRAF status, the 2 markers exhibited a more marked influence. Patients lacking the BRAF mutation and exhibiting normal levels of TTF1 exhibited very low levels of disease recurrence (11% at 10 years). Conversely, patient tumors with low levels of TTF1 and the BRAF mutation recurred in 31% of cases in the same time frame. The mixed expression of BRAF under varying levels of differentiation may explain, in part, the contradictory studies regarding the impact of BRAF mutations on patient prognosis and also indicates a complex genomic signature for dedifferentiated thyroid cancer.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db5a985a2fde8de6049154cb99acc890Test
https://doi.org/10.1016/j.humpath.2019.06.002Test -
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المؤلفون: Jason C. Chang, John H. Healey, Chad M. Vanderbilt, Meera Hameed, Marc Ladanyi, Sounak Gupta, Nasrin Islamdoust, Deepu Alex, Khedoudja Nafa, Tatsuo Ito, Yanming Zhang
المصدر: Hum Pathol
مصطلحات موضوعية: Adult, Male, Vascular Endothelial Growth Factor A, 0301 basic medicine, Adolescent, Gene Dosage, Bone Neoplasms, Core Binding Factor Alpha 1 Subunit, Locus (genetics), Genomics, Computational biology, Biology, Article, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Biomarkers, Tumor, medicine, Transcriptional regulation, Humans, Genetic Predisposition to Disease, Cyclin D3, Child, Gene, In Situ Hybridization, Fluorescence, Osteosarcoma, medicine.diagnostic_test, Hybridization capture, Gene Expression Profiling, Gene Amplification, High-Throughput Nucleotide Sequencing, Middle Aged, medicine.disease, RUNX2, Phenotype, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, Fluorescence in situ hybridization
الوصف: Prior cytogenetic profiling of osteosarcomas has suggested that amplifications at the 6p12-21 locus are relatively common alterations in these tumors. However, these studies have been limited by variable testing methodologies used as well as by the relatively small numbers of cases that have been analyzed. To better define the frequency of this alteration, 111 osteosarcomas were profiled using hybridization capture-based next-generation sequencing (NGS) platform (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) as part of an institutional clinical cancer genomics initiative. Using this platform, amplification at the 6p12-21 locus was determined by copy number assessment of the VEGFA and CCND3 genes. In addition, fluorescence in situ hybridization was used to assess copy number status for RUNX2, a known transcriptional regulator of osteoblastic differentiation which has previously been reported to be dysregulated in osteosarcomas. 6p12-21 amplification using NGS-based copy number assessment was confirmed in more than a fifth of all cases tested (24 of 111, 21.6%). Most of these cases, when tested using fluorescence in situ hybridization, were found to include RUNX2 within the amplified locus (17 of 18, 94.4%). Whereas many laboratories lack access to large-panel NGS assays, the use of fluorescence in situ hybridization to identify 6p12-21 amplification events by targeting RUNX2 represents a widely available diagnostic modality for the identification of such cases. This could help better define the role of RUNX2 in osteoblastic differentiation and serve as a surrogate for the identification of potentially targetable alterations such as VEGFA amplification at this locus.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::840a2759a6fccf2c691c936a476e2d3eTest
https://doi.org/10.1016/j.humpath.2019.09.010Test -
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المؤلفون: Anna Sebestyén, Yanyan Lou, Judit Pápay, Tracy L. Majewicz, Ildikó Krencz, Andras Khoor, Gabrielle F. Lutz
المصدر: Human Pathology. 93:74-80
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Lung Neoplasms, mTORC1, Mechanistic Target of Rapamycin Complex 1, Biology, RICTOR Gene, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Lymph node, In Situ Hybridization, Fluorescence, PI3K/AKT/mTOR pathway, Aged, medicine.diagnostic_test, digestive, oral, and skin physiology, Gene Amplification, Middle Aged, medicine.disease, Immunohistochemistry, Small Cell Lung Carcinoma, Primary tumor, Rapamycin-Insensitive Companion of mTOR Protein, 030104 developmental biology, medicine.anatomical_structure, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Cancer research, Female, Fluorescence in situ hybridization
الوصف: Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancers and remains a challenging disease, with no significant improvement in the field of targeted therapies. The RICTOR gene (rapamycin-insensitive companion of mTOR [mammalian target of rapamycin]), which encodes a key structural (scaffold) protein of mTOR complex 2), has recently been identified as one of the most frequently amplified genes and a potential therapeutic target in SCLC. The aim of this study was to compare immunohistochemical (IHC) expression of Rictor and phospho-Akt (a downstream target of mTOR complex 2) with RICTOR amplification as detected by fluorescence in situ hybridization (FISH) in SCLC. RICTOR FISH and Rictor and phospho-Akt IHC staining were performed on 100 formalin-fixed, paraffin-embedded SCLC samples. RICTOR amplification was detected in 15 samples (15%). IHC positivity for Rictor and phospho-Akt was observed in 37 (37%) and 42 (42%) samples, respectively. Considering FISH as the diagnostic standard, the sensitivity and specificity of Rictor IHC were 93% and 73%, whereas the sensitivity and specificity of phospho-Akt IHC were 80% and 65%, respectively. Rictor expression was higher in distant metastases than in primary tumor samples and lymph node metastases. There was no association between RICTOR amplification and clinical outcome. However, high expression of either Rictor or phospho-Akt was associated with significantly decreased overall survival. In conclusion, IHC expression of Rictor correlates highly with RICTOR amplification. Therefore, Rictor IHC can be used as a cost-effective method to select patients for RICTOR FISH and, potentially, for mTORC1/2 inhibitor therapy.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0421b513734ef0f75e10c46a2b5bf643Test
https://doi.org/10.1016/j.humpath.2019.08.018Test -
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المؤلفون: Marián Švajdler, Michal Michal, Peter Švajdler, Zdeněk Kinkor, Roman Mezencev, Nikola Ptáková, Michael Michal, Petr Martinek, Szépe P
المصدر: Human Pathology. 88:39-47
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Lamellar bone, Collagen Type I, Pathology and Forensic Medicine, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Musculoskeletal Diseases, Fasciitis, Overdiagnosis, Child, Gene Rearrangement, business.industry, Osteoid, High-Throughput Nucleotide Sequencing, Extremities, Gene rearrangement, Myositis ossificans, Fibroblasts, Middle Aged, medicine.disease, Collagen Type I, alpha 1 Chain, 030104 developmental biology, Myositis Ossificans, Child, Preschool, 030220 oncology & carcinogenesis, Osteosarcoma, Female, Sarcoma, Bone Diseases, Fibro-osseous pseudotumor, business, Ubiquitin Thiolesterase
الوصف: Myositis ossificans (MO) and fibro-osseous pseudotumor of digits (FOPD) are localized, self-limiting bone-producing pseudosarcomatous lesions characterized by nodular fasciitis-like proliferation and osteoid and immature woven bone production, which may eventually develop into more mature lamellar bone. Traditionally, MO and FOPD were thought to be of reactive, non-neoplastic nature. USP6 gene rearrangement was recently reported as a consistent finding in MO and FOPD, thus expanding the spectrum of transient, USP6-rearranged neoplasms. COL1A1 was described as the fusion partner of USP6 in a subset of MO cases, but the fusion partners of USP6-rearranged FOPD have not been uncovered so far. Initially, we carefully reviewed all 27 cases of MO/FOPD from our archives, documenting the remarkable morphological overlap between both lesions. Sixteen cases were seen in consultation, and our review was requested to rule in or rule out tentative diagnoses by referring pathologists. Malignant diagnosis (osteosarcoma) was suggested by the submitting pathologists in 3 cases, whereas 7 cases were sent by the referring pathologists to "rule out sarcoma." In the following step, using next-generation sequencing, we confirmed the COL1A1-USP6 rearrangement in 5/7 cases of MO and found the same abnormality in 4/5 of FOPD. Overall, 9 of the 12 analyzable cases (75%) of MO and FOPD harbored this gene fusion. The presence of COL1A1-USP6 gene rearrangement in MO/FOPD links these lesions to other USP6-driven tumors and represents a very useful supportive marker, which may help to avoid overdiagnosis of MO/FOPD as a sarcoma.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58ca7f8fac0fa49a3a859ae1c779c0e9Test
https://doi.org/10.1016/j.humpath.2019.02.009Test -
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المؤلفون: Gabriel Acosta-Gonzalez, Jonathan N. Glickman, Kara Lombardo, Shaolei Lu, Madhu M. Ouseph, Murray B. Resnick
المصدر: Human Pathology. 83:115-123
مصطلحات موضوعية: Adenoma, Adult, Male, 0301 basic medicine, CD3, Programmed Cell Death 1 Receptor, Adenocarcinoma, MLH1, B7-H1 Antigen, Article, Pathology and Forensic Medicine, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Tumor Microenvironment, Humans, Medicine, neoplasms, Aged, biology, business.industry, Microsatellite instability, Middle Aged, medicine.disease, digestive system diseases, Immune checkpoint, stomatognathic diseases, 030104 developmental biology, Hyperplastic Polyp, Dysplasia, 030220 oncology & carcinogenesis, Colonic Neoplasms, Disease Progression, Cancer research, biology.protein, Immunohistochemistry, Intraepithelial lymphocyte, Female, business
الوصف: The serrated neoplasia pathway accounts for approximately 20% of colorectal carcinomas (CRCs). Sessile serrated adenomas (SSAs), the main precursor lesion of the serrated pathway, are molecularly driven by MLH1 promoter methylation and microsatellite instability (MSI) in their progression to CRC. MSI-high (MSI-H) lesions are highly immunogenic and associated with a high density of tumor-infiltrating lymphocytes. Our study's aim was to determine how the kinetics of this immune environment relates to SSAs in their progression through low-grade (SSA-LD) to high-grade dysplasia (SSA-HD) and CRC. We analyzed 74 cases (16 CRCs, 14 SSAs-HD, and 44 SSAs-LD). Cases of hyperplastic polyp and SSA without dysplasia were analyzed for comparison. MSI status, intraepithelial lymphocyte (IEL) density, and immune checkpoint expression were assessed by immunohistochemistry for mismatch repair proteins, CD3, and PD-1/PD-L1, respectively. Average IEL density was 12, 18.6, 21.6, and 31 for SSA, SSA-LD, SSA-HD, and CRC, respectively, as opposed to 8.1 in normal colon (P < .0001). Average PD-1/PD-L1 lymphocytic expression was 1.1/1.0, 1.2/2.9, 4.8/6.9, and 12.4/15.2 in SSA, SSA-LD, SSA-HD, and CRC, respectively, compared with 0.5/0 in normal crypts (P < .0001). IEL and PD-1/PD-L1 lymphocytic expression values of MSI-H lesions were 22.6, 27.7, and 36.8, and 3/6.5, 6.2/10.6, and 18.3/17.6 in MSI-H SSA-LD, SSA-HD, and CRCs, respectively (P ranged from .0478 to .3529). PD-L1 epithelial expression was positive in 40% of SSAs, 59.1% of SSAs-LD, 100% of SSAs-HD, and 60% of CRCs (P < .0001). Increased IELs and PD-1/PD-L1 expression correlate with sequential progression of SSAs, through development of cytologic dysplasia, to CRC and MSI-H status.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::23b53c5a920c2a5297874c734902cd56Test
https://doi.org/10.1016/j.humpath.2018.08.020Test -
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المؤلفون: Shuchun Zhao, Kelly A. Devereaux, Matt van de Rijn, Vivek Charu, Charles D. Bangs, Yasodha Natkunam, Athena M. Cherry, Gregory W. Charville
المصدر: Human Pathology. 82:39-45
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Adolescent, Databases, Factual, Immune checkpoint inhibitors, Malignancy, medicine.disease_cause, B7-H1 Antigen, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Neoplasms, PD-L1, Biomarkers, Tumor, medicine, Humans, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, medicine.diagnostic_test, biology, business.industry, Cell Differentiation, Middle Aged, Immune dysregulation, Programmed Cell Death 1 Ligand 2 Protein, medicine.disease, Immunohistochemistry, Immune checkpoint, Blockade, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Female, Immunotherapy, Chromosomes, Human, Pair 9, business, Signal Transduction, Fluorescence in situ hybridization
الوصف: Undifferentiated malignancies (UMs) encompass a diverse set of aggressive tumors that pose not only a diagnostic challenge but also a challenge for clinical management. Most tumors in this category are currently treated empirically with nonspecific chemotherapeutic agents that yield extremely poor clinical response. Given that UMs are inherently genetically unstable neoplasms with the potential for immune dysregulation and increased neoantigen production, they are likely to be particularly amenable to immune checkpoint inhibitors, which target programmed cell death protein 1 (PD-1) or its ligands, PD-L1 and PD-L2, to promote T-cell antitumor activity. Aberrant expression of PD-L1 and, more recently, chromosomal 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) alterations can be used as biomarkers to predict responsiveness to checkpoint inhibitors. Here we evaluated 93 cases previously diagnosed as an "undifferentiated" malignancy and found that 56% (52/93) of UMs moderately to strongly express PD-L1 by immunohistochemistry (IHC). Concurrent CD274(PD-L1) and PDCD1LG2(PD-L2) fluorescence in situ hybridization (FISH) was performed on 24 of these cases and demonstrates a genetic gain at both loci in 62.5% of UMs. Genetic alterations at the CD274(PD-L1) and PDCD1LG2(PD-L2) loci were found to be completely concordant by FISH. Overall, we found that a significant proportion of UMs express PD-L1 and provide molecular support for using checkpoint inhibitors as a treatment approach for this class of tumors.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2224d4f590da0317c0534d167eb12094Test
https://doi.org/10.1016/j.humpath.2018.06.034Test -
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المؤلفون: Yanfeng Yang, Wansheng Gao, Yushi Zhang, Dongsheng Li, Zhi-yong Wang, Jin-xing Wei, Shuqiang Li
المصدر: Human Pathology. 82:61-67
مصطلحات موضوعية: Male, 0301 basic medicine, Biopsy, DNA Mutational Analysis, Gene mutation, Gastroenterology, Tuberous Sclerosis Complex 1 Protein, Tuberous sclerosis, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Genotype, Child, High-Throughput Nucleotide Sequencing, Kidney Neoplasms, Tumor Burden, Phenotype, medicine.anatomical_structure, Mutation (genetic algorithm), Female, Adult, China, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adolescent, Angiomyolipoma, Risk Assessment, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Internal medicine, Tuberous Sclerosis Complex 2 Protein, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Creatinine, business.industry, medicine.disease, nervous system diseases, 030104 developmental biology, chemistry, Mutation, Hemoglobin, TSC1, TSC2, Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
الوصف: TSC2 gene mutation was repeatedly reported to be associated with a more severe phenotype in patients with tuberous sclerosis complex (TSC). Our current study aims to further explore whether there is such a correlation in patients with TSC-associated renal angiomyolipoma (TSC-RAML). TSC1/TSC2 gene mutation was screened by high-throughput sequencing in 25 TSC-RAML patients from 2 medical centers. Clinical data were also carefully collected. Linear regression analysis and Student t-test were conducted by IBM SPSS Statistics Version 21.0 to analyze the genotypic-phenotypic relationship. The results indicated a high level of TSC gene mutation (80%; 20/25) in TSC-RAML patients, with higher frequency of TSC2 mutation (68%; 17/25) than TSC1 mutation (12%; 3/25). Seven novel mutation sites were detected in this study. In general, there were no significant correlations between tumor size and age (r = 0.134, P = .522), hemoglobin (r = 0.255, P = .219), and serum creatinine (r = 0.043, P = .839). Patients with larger tumor size have higher risk of bleeding. Specially, it was higher hemoglobin level in patients with TSC1 mutation than ones with TSC2 mutation and without TSC mutation (P.05). However, no difference was found in either tumor size or serum creatinine by TSC mutation genes (P.05). Furthermore, no difference was found in tumor size, hemoglobin, and serum creatinine by TSC mutation types (P.05). In conclusion, TSC-RAML is TSC2 mutation dominant, with the individual differences varying greatly. No definite genotype-phenotype correlation exists in patients with TSC-RAML, and it needs to be further explored.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7ffbca3bc34266cf2d80e1b6cf4cb94Test
https://doi.org/10.1016/j.humpath.2018.07.017Test -
9
المؤلفون: Roberta Cerutti, Nora Sahnane, Laura Mannarino, Laura Libera, Sergio Marchini, Cristina Riva, Daniela Furlan, Anna Maria Chiaravalli, Ilaria Craparotta
المصدر: Human Pathology. 81:235-244
مصطلحات موضوعية: 0301 basic medicine, ARID1A, Base Pair Mismatch, DNA Mutational Analysis, medicine.disease_cause, 0302 clinical medicine, Endometrial cancer, Lynch syndrome, MLH1 silencing, MMR defect, Targeted sequencing, 2734, High-Throughput Nucleotide Sequencing, Nuclear Proteins, Middle Aged, Immunohistochemistry, DNA-Binding Proteins, Phenotype, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, DNA mismatch repair, KRAS, MutL Protein Homolog 1, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Biology, Pathology and Forensic Medicine, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Predictive Value of Tests, Biomarkers, Tumor, medicine, Humans, PTEN, Genetic Predisposition to Disease, Gene Silencing, Epigenetics, Aged, Gene Expression Profiling, Microsatellite instability, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Endometrial Neoplasms, 030104 developmental biology, MSH2, Mutation, Cancer research, biology.protein, Transcription Factors
الوصف: Summary About one-third of endometrial carcinomas (ECs), mainly of endometrioid histology, harbor the mismatch repair (MMR) defects and microsatellite instability (MSI). Among these, ECs arising in women with Lynch syndrome (LS) account for a large proportion. To date, no somatic genetic analyses have been published comparing LS-ECs with sporadic ECs. In this work, we examined the mutational profiles of a well-characterized series of sporadic and LS-related ECs, performing exonic targeted sequencing of 16 genes mainly involved in MSI ECs. Next-generation sequencing analysis was performed in 35 ECs on the MiSeq platform (Illumina, San Diego, CA), and the mutational profile was analyzed integrating molecular and immunohistochemical data. PTEN, ARID1A, and ARID2 were the most frequently mutated genes regardless of MSI status or family history. MSI ECs showed a higher mutational load than MMR-proficient cases, exhibiting an MMR-deficient mutational signature. Among MSI tumors, LS-related and sporadic ECs exhibited similar mutational profiles, with MSH2 as the most commonly mutated gene. KRAS mutations seemed to be more common in sporadic MSI ECs than in LS-related ECs even if further studies are needed to confirm this finding. MMR-deficient ECs carried a higher mutational load and an excess of C>T transitions compared with MMR-proficient ECs, suggesting that the use of a small gene panel may be adequate to highlight significant differences between these 2 groups. An integrated analysis of genetic and epigenetic features of LS-related and sporadic ECs provides useful insights into disease biology and diagnostic classification of these tumors.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbd4f8da6df20ce2616636e1e5f58039Test
https://doi.org/10.1016/j.humpath.2018.06.029Test -
10
المؤلفون: Juliana Pereira, Jenna Weber, Shuchun Zhao, Benjamin A. Pinsky, Luis Alberto de Padua Covas Lage, Maria Claudia Nogueira Zerbini, Cristiane R. Ferreira, Malaya K. Sahoo, Yasodha Natkunam
المصدر: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USPمصطلحات موضوعية: Adult, Male, 0301 basic medicine, CD30, Regulatory T cell, T cell, Lymphoma, T-Cell, T-Lymphocytes, Regulatory, Pathology and Forensic Medicine, VÍRUS ONCOGÊNICOS, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, medicine, Humans, Cytotoxic T cell, Anaplastic Lymphoma Kinase, Anaplastic large-cell lymphoma, Aged, Human T-lymphotropic virus 1, business.industry, Lymphoma, T-Cell, Peripheral, Receptor Protein-Tyrosine Kinases, FOXP3, Forkhead Transcription Factors, Middle Aged, medicine.disease, Lymphoma, Leukemia, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Lymphoma, Large-Cell, Anaplastic, business, Biomarkers
الوصف: Summary Forkhead box P3 (FOXP3) is a specific marker for regulatory T-cells (Tregs). We report 6 cases of T-cell lymphomas with Treg phenotype based on diffuse positivity for FOXP3 in tumor cells. The patients showed a median age of 56 years with a male predominance. Sites of disease included lymph nodes (4), skin (2), subcutaneous tissue (1) and bone marrow (1). All cases showed monomorphic large cells, some with Hodgkin-like or anaplastic cells. All cases expressed pan T-cell markers and lacked cytotoxic markers; one case showed diffuse PD1 staining. Only one case harbored human T-lymphotrophic virus (HTLV)-1 DNA within tumor cells and was classified as adult T-cell leukemia/lymphoma (ATLL). Among 5 HTLV1-negative cases, 3 were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 2 fulfilled criteria for ALK-negative anaplastic large cell lymphoma (ALCL) with diffuse and strong CD30 positivity. We concluded that Treg phenotype may be rarely seen in HTLV1-negative cases, such as PTCL, NOS and ALK-negative ALCL. Our findings expand the spectrum of T-cell lymphomas with regulatory phenotype and suggest that consideration should be given to HTLV1 DNA testing in the appropriate clinical setting to rule out ATLL.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8cae297678d9483932624450a5b27054Test
https://doi.org/10.1016/j.humpath.2018.06.001Test
