STING is a molecule involved in immune reactions against double-stranded DNA fragments, released in infective and neoplastic diseases, whose role in the interactions between immune and neoplastic cells in clear cell renal cell carcinoma has not been studied yet. We investigated the immunohistochemical expression of STING in a series of 146 clear-cell renal cell carcinomas and correlated it with the main pathological prognostic factors. Furthermore, tumoral inflammatory infiltrate was evaluated and studied for the subpopulations of lymphocytes. Expression of STING was observed in 36% (53/146) of the samples, more frequently in high-grade (G3-G4) tumors (48%,43/90) and recurrent/metastatic ones (75%, 24/32) than in low grade (G1-G2) and indolent neoplasms (16%, 9/55). STING staining correlated with parameters of aggressive behavior, including coagulative granular necrosis (p = 0.001), stage (p < 0.001), and development of metastases (p < 0.001). Among prognostic parameters, STING immune expression reached an independent statistical significance (p = 0.029) in multivariable analysis, along with the stage and the presence of coagulative granular necrosis. About tumor immune-environment, no significant statistical association has been demonstrated between tumor-infiltrating lymphocytes and STING. Our results provide novel insights regarding the role of STING in aggressive clear cell renal cell carcinomas, suggesting its adoption as a prognostic marker and a potentially targetable molecule for specific immunotherapies.
Virchows Archiv : an international journal of pathology. 2023 Apr 29 [Epub ahead of print]
Stefano Marletta, Anna Caliò, Giuseppe Bogina, Mimma Rizzo, Matteo Brunelli, Serena Pedron, Lisa Marcolini, Lavinia Stefanizzi, Stefano Gobbo, Alessandro Princiotta, Camillo Porta, Angela Pecoraro, Alessandro Antonelli, Guido Martignoni
Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Largo L. Scuro 10, 37134, Verona, Italy., Department of Pathology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy., Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy., Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Italy., Department of Translational Medicine, University of Ferrara, Ferrara, Italy., Department of Urology, University of Verona, Verona, Italy., Interdisciplinary Department of Medicine, University of Bari "A. Moro,", Bari, Italy., Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy., Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Largo L. Scuro 10, 37134, Verona, Italy. .