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TCEB1-mutated renal cell carcinoma: a distinct genomic and morphological subtype
- Source :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Integrated sequencing analysis identified a group of tumors among clear cell renal cell carcinomas characterized by hotspot mutations in TCEB1 (a gene that contributes to the VHL complex to ubiquitinate hypoxia-inducible factor). We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. All tumors were characterized by hotspot mutations in TCEB1 Y79C/S/F/N or A100P. Morphological and immunohistochemical characteristics of the tumors were assessed by two experienced genitourinary pathologists. Clinical and pathological variables, copy number alterations, mutations, and expression signatures were compared with a cohort of TCEB1 wild-type tumors. All TCEB1-mutated tumors were VHL and PBRM1 wild type and contained distinct copy number profiles including loss of heterozygosity of chromosome 8, the location of TCEB1 (8q21.11). All tumors lacked the clear cell renal cell carcinoma signature 3p loss and contained distinct gene expression signatures. None of the clear cell papillary tumors harbored TCEB1 mutations. Pathologically, all TCEB1-mutated tumors shared characteristic features including thick fibromuscular bands transecting the tumor, pure clear cell cytology frequently with cells showing voluminous cytoplasm, and clear cell renal cell carcinoma-like acinar areas associated with infolding tubular and focally papillary architecture. The presence of voluminous cytoplasm, absence of luminal polarization of tumor nuclei, and lack of extensive cup-like distribution of carbonic anhydrase-IX expression distinguish it from clear cell papillary carcinoma. None of the patients developed metastases at last follow-up (median 48 months). In sum, TCEB1-mutated renal cell carcinoma is a distinct entity with recurrent hotspot mutations, specific copy number alterations, pathway activation, and characteristic morphological features. Further clinical follow-up is needed to determine whether these tumors are more indolent compared with the conventional clear cell renal cell carcinoma.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
DNA Mutational Analysis
Elongin
Cell
Biology
Article
Pathology and Forensic Medicine
PBRM1
TCEB1
Renal cell carcinoma
VHL
Biomarkers, Tumor
Carcinoma
medicine
Humans
Carcinoma, Renal Cell
Aged
Renal Cell Carcinoma
Genomics
Middle Aged
medicine.disease
Clear cell papillary renal cell carcinoma
Immunohistochemistry
Kidney Neoplasms
3. Good health
Clear cell renal cell carcinoma
medicine.anatomical_structure
Cytoplasm
Mutation
Female
Clear cell
Transcription Factors
Subjects
Details
- ISSN :
- 08933952
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Modern Pathology
- Accession number :
- edsair.doi.dedup.....c32e1818303a7a02c5e170fcea8adfcd