PMID- 22892601
OWN - NLM
STAT- MEDLINE
DCOM- 20121203
LR  - 20211021
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 36
IP  - 10
DP  - 2012 Oct
TI  - Molecular confirmation of t(6;11)(p21;q12) renal cell carcinoma in archival 
      paraffin-embedded material using a break-apart TFEB FISH assay expands its 
      clinicopathologic spectrum.
PG  - 1516-26
LID - 10.1097/PAS.0b013e3182613d8f [doi]
AB  - A subset of renal cell carcinomas (RCCs) is characterized by t(6;11)(p21;q12), 
      which results in fusion of the untranslated Alpha (MALAT1) gene to the TFEB gene. 
      Only 21 genetically confirmed cases of t(6;11) RCCs have been reported. This 
      neoplasm typically demonstrates a distinctive biphasic morphology, comprising 
      larger epithelioid cells and smaller cells clustered around basement membrane 
      material; however, the full spectrum of its morphologic appearances is not known. 
      The t(6;11) RCCs differ from most conventional RCCs in that they consistently 
      express melanocytic immunohistochemical (IHC) markers such as HMB45 and Melan A 
      and the cysteine protease cathepsin K but are often negative for epithelial 
      markers such as cytokeratins. TFEB IHC has been proven to be useful to confirm 
      the diagnosis of t(6;11) RCCs in archival material, because native TFEB is 
      upregulated through promoter substitution by the gene fusion. However, IHC is 
      highly fixation dependent and has been proven to be particularly difficult for 
      TFEB. A validated fluorescence in situ hybridization (FISH) assay for molecular 
      confirmation of the t(6;11) RCC in archival formalin-fixed, paraffin-embedded 
      material has not been previously reported. We report herein the development of a 
      break-apart TFEB FISH assay for the diagnosis of t(6;11)(p21;q12) RCCs. We 
      validated the assay on 4 genetically confirmed cases and 76 relevant expected 
      negative control cases and used the assay to report 8 new cases that expand the 
      clinicopathologic spectrum of t(6;11) RCCs. An additional previously reported 
      TFEB IHC-positive case was confirmed by TFEB FISH in 46-year-old archival 
      material. In conclusion, TFEB FISH is a robust, clinically validated assay that 
      can confirm the diagnosis of t(6;11) RCC in archival material and should allow a 
      more comprehensive clinicopathologic delineation of this recently recognized 
      neoplastic entity.
FAU - Argani, Pedram
AU  - Argani P
AD  - Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 
      21231-2410, USA. pargani@jhmi.edu
FAU - Yonescu, Raluca
AU  - Yonescu R
FAU - Morsberger, Laura
AU  - Morsberger L
FAU - Morris, Kerry
AU  - Morris K
FAU - Netto, George J
AU  - Netto GJ
FAU - Smith, Nathan
AU  - Smith N
FAU - Gonzalez, Nilda
AU  - Gonzalez N
FAU - Illei, Peter B
AU  - Illei PB
FAU - Ladanyi, Marc
AU  - Ladanyi M
FAU - Griffin, Constance A
AU  - Griffin CA
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Validation Study
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (TFEB protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics/metabolism
MH  - Carcinoma, Renal Cell/*genetics/secondary
MH  - Child, Preschool
MH  - *Chromosomes, Human, Pair 11
MH  - *Chromosomes, Human, Pair 6
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Kidney Neoplasms/*genetics/pathology
MH  - Liver Neoplasms/genetics/secondary
MH  - Male
MH  - Middle Aged
MH  - Paraffin Embedding
MH  - *Translocation, Genetic
PMC - PMC4441265
MID - NIHMS682076
COIS- 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.
EDAT- 2012/08/16 06:00
MHDA- 2012/12/10 06:00
PMCR- 2015/05/22
CRDT- 2012/08/16 06:00
PHST- 2012/08/16 06:00 [entrez]
PHST- 2012/08/16 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2015/05/22 00:00 [pmc-release]
AID - 10.1097/PAS.0b013e3182613d8f [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2012 Oct;36(10):1516-26. doi: 10.1097/PAS.0b013e3182613d8f.