Stimulator of interferon genes (STING) immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney

Angiomyolipoma is the prototype of renal perivascular epithelioid cell (PEC) lesions whose pathogenesis is determined by mutations affecting TSC genes, with eventual deregulation of the mTOR pathway. It is well known that mTOR complex protein is involved in autophagy, and recently the role of STING in this process has been demonstrated. Based on this background, we sought to investigate STING immunohistochemical expression in a series of PEC lesions of the kidney. Fifty classic angiomyolipomas, 14 epithelioid angiomyolipomas/pure epithelioid PEComas, two angiomyolipomas with epithelial cysts (AMLEC), and two intraglomerular PEC lesions were collected. Immunostaining for STING was carried out in all cases and FISH analysis using dual colour break apart TFE3 and TFEB probes was performed in all pure epithelioid PEComas and AMLEC. Control cases including 20 normal adult kidneys, five fetal kidneys, and 30 MiT family translocation renal cell carcinomas (the main differential diagnosis with epithelioid angiomyolipoma/pure epithelioid PEComa) were also immunohistochemically stained with STING. Strong and diffuse cytoplasmic expression of STING was observed in 100% of classic angiomyolipomas, AMLEC, and intraglomerular lesions, and in 79% (11/14) of epithelioid angiomyolipomas/pure epithelioid PEComas. TFE3 gene rearrangement was demonstrated in two epithelioid angiomyolipomas/pure epithelioid PEComas, both completely negative for STING. None of the MiT family translocation renal cell carcinomas expressed STING. In conclusion, we demonstrate the expression of STING in almost all PEC lesions of the kidney. This result provides novel insights into the possible role of autophagy in PEC lesions of the kidney. Moreover, this finding may be useful for diagnostic purposes, particularly in distinguishing epithelioid angiomyolipoma/pure epithelioid PEComa from MiT family translocation renal cell carcinoma and detecting intraglomerular PEC lesions.