TFE3 Break-Apart FISH Has a Higher Sensitivity for Xp11.2 Translocation-Associated Renal Cell Carcinoma Than TFE3 or Cathepsin K Immunohistochemical Staining Alone: Expanding the Morphologic Spectrum2013-06-01 18:34:02
The American Journal of Surgical Pathology; 2013 June; 37(6):804-15
Qiu Rao, Sean R Williamson, Shaobo Zhang, John N Eble, David J Grignon, Mingsheng Wang, Xiao-jun Zhou, Wenbin Huang, Puay-Hoon Tan, Gregory T MacLennan, Liang Cheng
Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by various translocations involving the TFE3 gene. Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by various translocations involving the TFE3 gene. Recognition commonly depends on nuclear overexpression of TFE3 protein by immunohistochemistry (IHC), although staining can be variable. Break-apart fluorescence in situ hybridization (FISH) for TFE3 has shown promise for detecting these gene alterations.
We assessed the utility of break-apart fluorescence in situ hybridization (FISH) in establishing the diagnosis for suspected or unclassified cases with negative or equivocal TFE3 immunostaining by analyzing 24 renal cancers with break-apart TFE3 FISH and comparing the molecular findings to the results of TFE3 and cathepsin K immunostaining in the same tumors. Ten tumors were originally diagnosed as Xp11.2 RCC based upon positive TFE3 immunostaining and 14 were originally considered unclassified RCCs with negative or equivocal TFE3 staining, but with a range of features suspicious for Xp11.2 RCC.
Seventeen cases showed TFE3 rearrangement associated with Xp11.2 translocation by FISH, including all tumors with moderate or strong TFE3 (n=10) or cathepsin K (n=7) immunoreactivity. FISH-positive cases showed negative or equivocal immunoreactivity for TFE3 or cathepsin K in seven and ten tumors, respectively. None had positive IHC but negative FISH. Morphologic features were typical for Xp11.2 RCC in 10/17 tumors. Unusual features included one melanotic Xp11.2 renal cancer, one tumor with mixed features of Xp11.2 RCC and clear cell RCC, and other tumors mimicking clear cell RCC, multilocular cystic RCC, or high grade urothelial carcinoma. Psammoma bodies, hyalinized stroma, and intracellular pigment were commonly present in FISH-positive cases compared to FISH-negative cases.
Our study supports the utility of break-apart FISH in enhancing the detection of Xp11.2 RCCs and further expands the histopathologic spectrum of these neoplasms to include tumors with unusual features.
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