Stimulator of interferon genes immunohistochemical expression in the spectrum of extrarenal perivascular epithelioid cell lesions.

Angiomyolipoma is the prototype of the perivascular epithelioid cells (PEC) lesions whose pathogenesis is usually determined by mutations of the TSC1/2 genes, with eventual deregulation of the mTOR pathway, whereas a small subset of PEComas is driven by rearrangements of the TFE3 gene. It is well known that the mTOR complex protein is involved in autophagy, and the role of STING has recently been demonstrated in this process. As relevant STING immunolabelling in the PEC lesions of the kidney has already been reported, we sought to further investigate the immunohistochemical expression of this marker in a series of extrarenal PEComas. Thirty-nine PEComas from different sites (17 uterus, 5 lungs, 4 pancreas, 4 retroperitoneum, 3 soft tissues, 3 liver, 1 lymph node, 1 bowel, and 1 urinary bladder) were collected from 36 patients, including 35 primary tumors and 4 distant metastases. The cohort encompassed 27 epithelioid PEComas, 8 clear cell sugar tumors, and 4 lymphangioleiomyomatoses. Immunostaining for STING was carried out. Strong and diffuse immunolabeling of STING was documented in 90% of PEComas (35/39), with concordant expression in primary and metastatic samples (4/4, 100%). No TFE3 gene rearrangement was documented by FISH, although one STING-negative case showed minimally split fluorescent signals separated by a signal diameter. Our findings support the hypothesis of a STING-mediated alteration of the autophagic process in the PEComas and suggest a potential biological and therapeutic role for this marker and its related pathway.