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Detection of the ASPL-TFE3 and PRCC-TFE3 gene fusion in paraffin-embedded Xp11 translocation renal cell carcinomas

2016-11-15 18:58:58

International Journal of Clinical and Experimental Pathology; 15 November 2016: /ISSN:1936-2625/IJCEP0030001

Zi-Yu Wang, Qiu-Yuan Xia, Shan-Shan Shi, Sheng-Bing Ye, Rui Li, Heng-Hui Ma, Zhen-Feng Lu, Xiao-Jun Zhou, Qiu Rao



Abstract


Xp11 translocation renal cell carcinomas (RCCs) are uncommon renal tumors, characterized by several
different translocations involving the TFE3 gene. In these diseases, the TFE3 gene is fused by translocation to 1
of several other genes, including ASPL, PRCC, NONO (p54nrb), CLTC, PSF, LUC7L3, KHSRP, PARP14 and unknown
genes on chromosomes 10. Tumors with different specific gene fusions may have slightly different clinical manifestations and morphologic features. In this study, we developed a FISH assay to detect the TFE3 gene rearrangement for the presence of the 2 most common fusion genes ASPL-TFE3 and PRCC-TFE3 inroutinely processed archival materials. 10 Xp11 translocation RCCs were detected TFE3 fusion genes. Cases 1-6 displayed fusion signals of ASPL-TFE3 and cases 7-10 demonstrated fusion signals of PRCC-TFE3. All cases contained a high percentage of
cells displaying fusion signals for ASPL-TFE3 (mean, 45%; range, 35% to 60%) and for PRCC-TFE3 (mean, 45%;
range, 35% to 60%). The sensitivity and specificity were both 100%. The interphase fluorescencein situ hybridization (FISH) assays should enable a more definitive identification of the ASPL-TFE3 and PRCC-TFE3 fusion gene in archival material and allow more meaningful clinicopathologic associations to be drawn.



Introduction


Xp11 translocation renal cell carcinomas (RCCs) are uncommon renal tumors, characterized by several different translocations involving the TFE3 gene. In these diseases, the TFE3 gene is fused by translocation to 1 of several other genes, including ASPL, PRCC, NONO (p54nrb), CLTC, PSF, LUC7L3, KHSRP, PARP14 and unknown genes on chromosomes 10 [1-8]. The t(X;17)(p11.2;q25) translocation with ASPLTFE3 fusion and the t(X;1)(p11.2;q21) translocation with PRCC-TFE3 fusion are the 2 most common forms. Tumors with different specific gene fusions may have slightly different clinical manifestations and morphologic features. For example, ASPL-TFE3-associated tumors frequently present at an advanced stage and distinctive features including voluminous clear cytoplasm, discrete cell borders, an alveolar or papillary growth pattern, and psammoma bodies, whereas PRCC-TFE3-associated neoplasms tend to possess a nested growth pattern, smaller cells with less abundant cytoplasm, and fewer calcifications. The difference and significance of clinical manifestations from different gene fusions remain to be explored.



Xp11 translocation RCCs can be diagnosed through detection of TFE3 protein overexpression by immunohistochemistry and TFE3 gene rearrangements by TFE3 break-apart fluorescencein situ hybridization (FISH) assays. However, both methods do not provide information as to the specific fusion partners of TFE3. Cytogenetic karyotypic analysis and reverse transcriptase polymerase chain reaction (RTPCR) are 2 common methodologies for identifying the specific gene fusions. Unfortunately, both methods are limited by the need for special handling techniques and are not always easy to apply in routine diagnostic practice. Therefore the specific gene fusions of
Xp11 translocation RCCs were rarely confirmed and described in case reports or small series.



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Key Words

Xp11 translocation renal cell carcinoma | rearrangement | translocation | TFE3 | ASPL | PRCC | FISH | molecular genetics