{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:21:09Z","timestamp":1784042469519,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:p><jats:italic>RICTOR<\/jats:italic> gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. <jats:italic>RICTOR<\/jats:italic> amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare <jats:italic>RICTOR<\/jats:italic> amplification detected by fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. <jats:italic>RICTOR<\/jats:italic> amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted <jats:italic>RICTOR<\/jats:italic> amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between <jats:italic>RICTOR<\/jats:italic> amplification and PD-L1 expression; <jats:italic>RICTOR<\/jats:italic> amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; <jats:italic>RICTOR<\/jats:italic> copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between <jats:italic>RICTOR<\/jats:italic> amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with <jats:italic>RICTOR<\/jats:italic> amplification. Since a significant proportion of PD-L1 negative SCC cases harbor <jats:italic>RICTOR<\/jats:italic> amplification, analyzing PD-L1 negative tumors by <jats:italic>RICTOR<\/jats:italic> FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.<\/jats:p>","DOI":"10.3389\/pore.2024.1611593","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T04:11:56Z","timestamp":1713499916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell 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