Background/aim: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors.
Patients And Methods: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed.
Results: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable.
Conclusion: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.
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http://dx.doi.org/10.21873/anticanres.14985 | DOI Listing |
Diagn Pathol
January 2025
Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, Prague, 12800, Czech Republic.
Background: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT.
Methods: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated.
Int J Mol Sci
December 2024
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Substantial loss of cardiomyocytes during heart attacks and onset of other cardiovascular diseases is a major cause of mortality. Preservation of cardiomyocytes during cardiac injury would be the most effective strategy to manage these diseases in clinic. However, there is no effective treatment strategy that is able to prevent cardiomyocyte loss.
View Article and Find Full Text PDFEMBO J
January 2025
Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China.
Small GTPase RHEB is a well-known mTORC1 activator, whereas neddylation modifies cullins and non-cullin substrates to regulate their activity, subcellular localization and stability. Whether and how RHEB is subjected to neddylation modification remains unknown. Here, we report that RHEB is a substrate of NEDD8-conjugating E2 enzyme UBE2F.
View Article and Find Full Text PDFIn Vivo
December 2024
Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;
Background/aim: Soft tissue sarcoma (STS) is a mesenchymal tumor affecting multiple organs in dogs. Previous studies identified activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB, AKT) pathway in canine STS cell lines and clinical samples, but the underlying mechanism remains unclear. This study investigated PTEN loss, PIK3CA mutation, and EGFR over-expression as potential drivers of PI3K/AKT pathway activation in STS.
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