title: t(6;11) renal cell carcinoma (RCC): expanded immunohistochemical profile emphasizing novel RCC markers and report of 10 new genetically confirmed cases.
abstract: Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cathepsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that metastasize.
authors.affiliation: Departments of *Pathology †Urology ‡Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD §Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY ∥Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Nathaniel E
authors.initials: NE
authors.lastname: Smith
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Mohamed
authors.initials: M
authors.lastname: Allaf
authors.forename: Nilda
authors.initials: N
authors.lastname: Gonzalez
authors.forename: Kerry
authors.initials: K
authors.lastname: Morris
authors.forename: Jessica
authors.initials: J
authors.lastname: Hicks
authors.forename: Angelo
authors.initials: A
authors.lastname: Demarzo
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor