Inactivation of phosphatase and tensin homolog (PTEN) is caused by multiple mechanisms, and loss of PTEN activity is related to the progression of various cancers. In gastric cancer (GC), the relationship between the loss of PTEN protein expression and various genetic alterations remains unclear. The effects of microsatellite instability (MSI), Epstein–Barr virus (EBV), HER2 overexpression, and PD-L1 expression on PTEN mutation have not been fully explored. We performed comprehensive cancer panel tests with a cohort of 322 tumor samples from patients with advanced GC. Immunohistochemistry for PTEN protein was performed in all cases, and the loss of protein expression was defined as a complete absence of nuclear staining. In total, 34 cases (10.6%) had pathogenic PTEN mutations, of which 19 (55.9%) showed PTEN protein loss. The most common PTEN variants associated with protein loss were p.R130 (n = 4) followed by p.R335, p.L265fs, and deletions (n = 2). All the ten nonsense mutations identified in the samples resulted in PTEN inactivation. In the remaining 288 GC cases with wild-type PTEN, protein loss was found in 35 cases (12.2%). Thus, PTEN mutations were significantly associated with PTEN protein loss (p = 5.232 × 10⁻¹⁰), high MSI (p = 3.936 × 10⁻⁸), and EBV-positivity (p = 0.0071). In conclusion, our results demonstrate that loss-of-function mutations in PTEN are a frequent genetic mechanism of PTEN inactivation in GC.

Exosomes are a subtype of extracellular vesicles ranging from 30 to 150 nm and comprising many cellular components, including DNA, RNA, proteins, and metabolites, encapsulated in a lipid bilayer. Exosomes are secreted by many cell types and play important roles in intercellular communication in cancer. Viruses can hijack the exosomal pathway to regulate viral propagation, cellular immunity, and the microenvironment. Cells infected with Epstein-Barr virus (EBV), one of the most common oncogenic viruses, have also been found to actively secrete exosomes, and studies on their roles in EBV-related malignancies are ongoing. In this review, we focus on the role of exosomes in EBV-associated gastric cancer and their clinical applicability in diagnosis and treatment.

BCOR-rearranged sarcoma was classified by the World Health Organization in 2020 as a new subgroup of undifferentiated small round-cell sarcoma. It is known to occur very rarely in the kidney. This report presents the first case of a primary renal BCOR::CCNB3 sarcoma in a 22-year-old woman. An 8-cm cystic mass was identified in the left kidney by abdominal pelvic computed tomography. Histopathologic examination revealed the mass to be composed of small round to oval or spindle cells with fibrous septa and a delicate vascular network. A BCOR::CCNB3 fusion was detected by next-generation sequencing–based molecular testing. BCOR::CCNB3 sarcoma presents diagnostic difficulties, highlighting the importance of recognizing its histological features. Immunohistochemical markers are helpful for diagnosis, but genetic molecular testing is necessary for accurate diagnosis. These tumors have a very poor and aggressive prognosis, and an optimal therapeutic regimen has not yet been defined. Therefore, further studies are needed.

Undifferentiated pancreatic carcinoma with osteoclast-like giant cells (UC-OGC) is uncommon, accounting for only 1% of all pancreatic carcinomas. We report a case of a 39-year-old man with undifferentiated pancreatic carcinoma with osteoclast-like giant cells who underwent successful surgical resection and chemotherapy.