title: Utilization of a TFE3 break-apart FISH assay in a renal tumor consultation service.
abstract: Xp11 translocation renal cell carcinomas (RCCs) are characterized by chromosome translocations involving the Xp11.2 breakpoint, resulting in gene fusions involving the TFE3 transcription factor. In archival material, the diagnosis can often be confirmed by TFE3 immunohistochemistry (IHC), but variable fixation (especially prevalent in consultation material) can lead to equivocal results. A TFE3 break-apart fluorescence in situ hybridization (FISH) assay has been developed to detect TFE3 gene rearrangements; however, the utility of this assay in a renal tumor consultation practice has not been examined. We reviewed 95 consecutive renal tumor consultation cases submitted to rule in or rule out Xp11 translocation RCC. Thirty-one cases were positive for TFE3 rearrangements by FISH. Patients ranged from 6 to 67 years of age (mean=30 y; median=28 y). Novel or distinctive morphologic features of these cases included extensive cystic change simulating multilocular cystic RCC (3 cases), sarcomatoid transformation (3 cases), oncocytic areas mimicking oncocytoma (1 case), trabecular architecture mimicking a carcinoid tumor (1 case), colonization of renal pelvic urothelium mimicking urothelial carcinoma in situ (1), and focal desmin and diffuse racemase immunoreactivity (1 case each). Twenty-six of the 31 TFE3 FISH-positive RCCs were unequivocally positive for TFE3 by IHC, but 4 were equivocal, and 1 was negative. Of the 64 cases that were negative by TFE3 FISH, 50 were negative by TFE3 IHC, and 14 were equivocal. Thirty-two of the 64 TFE3 FISH-negative cases could be classified into other accepted RCC subtypes: 23 as clear cell RCC, 5 as papillary RCC, 3 as clear cell papillary RCC, and 1 as chromophobe RCC. The other 32 cases remained unclassified, including 3 cathepsin K-positive RCC that closely resembled Xp11 translocation RCC. In conclusion, TFE3 FISH is highly useful in renal tumor consultation material, often resolving cases with equivocal TFE3 IHC results. Given the difficulty of optimizing TFE3 IHC, TFE3 FISH is for most laboratories the optimal test for establishing the diagnosis of Xp11 translocation RCC.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Intuitions, Baltimore, MD 21231, USA.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Green
authors.forename: Raluca
authors.initials: R
authors.lastname: Yonescu
authors.forename: Laura
authors.initials: L
authors.lastname: Morsberger
authors.forename: Kerry
authors.initials: K
authors.lastname: Morris
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Mohamad
authors.initials: M
authors.lastname: Allaf
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Constance A
authors.initials: CA
authors.lastname: Griffin
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000032:analysis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002648:Child; D041321:Chromosomes, Human, X; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010338:Pathology, Clinical / Q000379:methods*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012017:Referral and Consultation; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D014408:Biomarkers, Tumor; C069203:TFE3 protein, human