ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2017
TFEB-VEGFA (6p21.1) co-amplified renal cell carcinoma: a distinct entity with potential implications for clinical management.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- New developments in existing WHO entities and evolving molecular concepts: The Genitourinary Pathology Society (GUPS) update on renal neoplasia.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Guideline
- Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer.The American journal of surgical pathology · 2020Guideline
- Sex- and age-specific associations ofAnnals of medicine · 2026Article
- Immunohistochemical expression of GPNMB in TFEB-rearranged and TFEB-amplified renal cell carcinomas.Virchows Archiv : an international journal of pathology · 2026Article
- Aggressive high-grade papillary-patterned renal cell carcinomas harboring FLCN mutations: expanding the clinicopathological spectrum in Birt-Hogg-Dubé syndrome and sporadic cases.Virchows Archiv : an international journal of pathology · 2026Article
- Review
- Molecularly defined renal cell carcinomas.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2026Review
- Review
- Systemic Treatment of Locally Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma.Cancers · 2025Review
- Bystin is a Prognosis and Immune Biomarker: From Pan-Cancer Analysis to Validation in Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- A clinicopathological and molecular series of five TFEB-altered renal cell carcinoma (RCC) cases: highlighting an aggressive subset of TFEB-rearranged RCC concomitant with TFEB amplification/gene copy number gains.Virchows Archiv : an international journal of pathology · 2024Article
- The Impact ofInternational journal of molecular sciences · 2024Article
- A rare case of TFEB/6p21/VEGFA-amplified renal cell carcinoma diagnosed by whole-exome sequencing: clinicopathological and genetic feature report and literature review.Diagnostic pathology · 2024Review
- Genomic profiling and molecular characterization of non-clear cell renal cell carcinoma: a narrative review from a clinical perspective.Therapeutic advances in medical oncology · 2024Review
- The post-translational regulation of transcription factor EB (TFEB) in health and disease.EMBO reports · 2023Review
- Clinical Characteristics of Molecularly Defined Renal Cell Carcinomas.Current issues in molecular biology · 2023Review
- Article
- Article
- Transcription factor EB as a key molecular factor in human health and its implication in diseases.SAGE open medicine · 2023Review
- Past, present, and future perspectives of transcription factor EB (TFEB): mechanisms of regulation and association with disease.Cell death and differentiation · 2022Review
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Authors and funding
11 authors.
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Abstract
A subset of renal cell carcinomas shows TFEB overexpression secondary to MALAT1-TFEB gene fusion. As alternate mechanisms of TFEB overexpression are likely to have the same effect, we sought to determine the frequency of amplification of TFEB and the adjacent VEGFA gene at 6p21.1. As patients with metastatic renal cell carcinomas are managed with anti-VEGF therapies, we retrospectively assessed therapeutic response in patients with amplified tumors. Amplification status was analyzed for 875 renal cell carcinomas from our institution, a consultative case and 794 cases from The Cancer Genome Atlas. Cases were classified as having low level (5-10 copies), and high-level amplification (>10 copies), and were further analyzed for adjacent oncogene copy number status (n=6; 3 single-nucleotide polymorphism genomic microarray, 3 The Cancer Genome Atlas) and structural rearrangements (n=1; mate-pair sequencing). These were then reviewed for histopathology, immunophenotype, and response to VEGF-targeted therapy on follow-up. In all, 10/875 (1.1%) institutional cases, 1 consultative case, and 3/794 (0.4%) of The Cancer Genome Atlas cases showed TFEB high-level amplification, while 14/875 (1.6%) cases showed TFEB low-level amplification. All cases had associated VEGFA amplification. This was confirmed with evaluation for copy number changes (n=6). The 6p21.1 high and low-level amplified tumors occurred in adults (mean age: 66), with over half being ≥pT3 (13/25, 52%), and most showed oncocytic, tubulopapillary features and high grade (≥grade 3: 20/22, 91%). These were aggressive tumors with metastasis and death from renal cell carcinoma in 11 (of 24, 46%) cases. Four patients received targeted therapy and had a mean survival of 31 months (range: 17-50) post nephrectomy. In summary, a group of aggressive renal cell carcinomas show genomic amplification of the 6p21.1 region including TFEB and VEGFA genes and share morphologic features. Additional studies are warranted to determine whether these patients respond to anti-VEGF therapy.
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