title: Xp11.2 translocation renal cell carcinoma with NONO-TFE3 gene fusion: morphology, prognosis, and potential pitfall in detecting TFE3 gene rearrangement.
abstract: Xp11 translocation renal cell carcinomas are characterized by several different translocations involving the TFE3 gene. Tumors with different specific gene fusions may have different clinicopathological manifestations. Fewer than 10 renal cell carcinoma cases with NONO-TFE3 have been described. Here we examined eight additional cases of this rare tumor using clinicopathological, immunohistochemical, and molecular analyses. The male-to-female ratio of our study cohort was 1:1, and the median age was 30 years. The most distinctive feature of the tumors was that they exhibited glandular/tubular or papillary architecture that was lined with small-to-medium cuboidal to high columnar cells with indistinct cell borders and an abundantly clear or flocculent eosinophilic cytoplasm. The nuclei were oriented toward the luminal surface and were round and uniform in shape, which resulted in the appearance of secretory endometrioid subnuclear vacuolization. The distinct glandular/tubular or papillary architecture was often accompanied by sheets of epithelial cells that presented a biphasic pattern. Immunohistochemically, all eight cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, CD10, RCC marker, and PAX-8. None of the tumors were immunoreactive for CK7, Cathepsin K, Melan-A, HMB45, Ksp-cadherin, Vimentin, CA9, 34βE12 or CD117. NONO-TFE3 fusion transcripts were identified in six cases by RT-PCR. All eight cases showed equivocal split signals with a distance of nearly 2 signal diameters and sometimes had false-negative results. Furthermore, we developed a fluorescence in situ hybridization (FISH) assay to serve as an adjunct diagnostic tool for the detection of the NONO-TFE3 fusion gene and used this method to detect the fusion gene in all eight cases. Long-term follow-up (range, 10-102 months) was available for 7 patients. All 7 patients were alive with no evidence of recurrent disease or disease progression after their initial resection. This report adds to the known data regarding NONO-TFE3 renal cell carcinoma.
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu-Yuan
authors.initials: QY
authors.lastname: Xia
authors.affiliation: Department of Pathology, State Key Laboratory of Cancer Biology, Xi Jing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Hua-Lei
authors.initials: HL
authors.lastname: Gan
authors.affiliation: Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Teng
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Sheng-Bing
authors.initials: SB
authors.lastname: Ye
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Heng-Hui
authors.initials: HH
authors.lastname: Ma
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Lu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Rao
mesh_terms: D000328:Adult; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D050810:Octamer Transcription Factors / Q000235:genetics*; D050596:Oncogene Fusion; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; C069203:TFE3 protein, human