Most follicular lymphomas (FLs) demonstrate an indolent clinical course with favorable outcomes; however, a fraction of patients experiences progression of disease within 24 months (POD24) and has adverse outcomes. This study aimed to determine the predictive risk factors for POD24 in patients with FL, and the characteristics of the microenvironment in FL with POD24. By multivariate analysis, we revealed that increased Ki-67 expression was associated with POD24 events in patients with FL (hazard ratio [HR]: 6.29, 95% confidence interval [CI]: 1.96–20.22, p = 0.0020). Additionally, patients with FL with POD24 demonstrated immune cell reduction by immunohistochemistry analysis. Our results help better understand the therapeutic strategies for FL with POD24.

The interplay between TP53 alterations and Wnt/β-catenin signaling in colorectal cancer (CRC) remains unclear regarding mismatch repair (MMR) status, tumor budding (TB), poorly differentiated cluster (PDC), and prognosis. We analyzed 146 resected CRC cases, quantifying p53, Wnt3, and β-CTN indices and assessing MMR by PMS2 and MSH6 immunohistochemistry. p53 overexpression was associated with younger patients, left-sided tumors, nodal metastasis, and advanced stage, whereas wild-type tumors showed more mucinous differentiation. Deficient MMR was enriched among wild-type p53 cases. Principal component analysis identified distinct axes defined by p53, Wnt3, and β-CTN. Despite comparable Wnt3 levels, nuclear β-CTN accumulation was enhanced in tumors with aberrant (overexpression or null) p53 tumors, with increased TB and PDC indices. Low nuclear β-CTN independently predicted recurrence in stage I–III disease and worse overall survival in proficient MMR tumors (HR 3.07 and 2.52; p = 0.03 for both). A composite score integrating p53 binary status (aberrant vs. wild) with Wnt3 and whole β-CTN indices predicted survival beyond stage; each 1-point increase conferred a 2.56- and 1.77-fold higher risk of cancer-specific and overall mortality (p = 0.004 and 0.04). These findings suggest that p53 dysfunction is associated with alterations in Wnt/β-CTN signaling and that integrating signaling markers with staging may improve prognostic assessment in colorectal cancer.

Objectives: Tenascin-C (TNC) is an extracellular matrix protein associated with tissue remodeling, tumor progression, and poor prognosis in breast cancer. Although TNC has attracted interest as a potential stromal biomarker, its baseline histopathological distribution in untreated breast cancer has not been fully characterized. This exploratory pilot study aimed to characterize the immunohistochemical distribution of TNC in representative treatment-naïve breast cancer tissues. Methods: Immunohistochemical staining for TNC was performed in representative breast cancer tissue specimens obtained from 16 treatment-naïve patients encompassing major histological and molecular subtypes. Tumor and non-tumor areas were evaluated descriptively by two board-certified pathologists using consensus assessment. Results: Heterogeneous TNC expression was observed in the stroma surrounding invasive tumors in all cases. In most specimens, TNC staining was predominantly localized to the peritumoral stroma, whereas occasional staining was observed around non-invasive lesions. Non-tumor breast stroma was largely negative, although positive staining was observed in biopsy scars and sclerotic areas. No consistent subtype-specific pattern of TNC distribution or staining intensity was identified. Conclusions: TNC showed heterogeneous stromal expression in treatment-naïve breast cancer and was also detected in biopsy scars and areas of stromal remodeling. These findings provide baseline histopathological information regarding TNC localization in untreated breast cancer. Further studies are required to determine the potential clinical utility of TNC as a stromal biomarker, including its application in the post-neoadjuvant setting.

Background: Boron neutron capture therapy (BNCT) is a type of targeted radiotherapy with considerable therapeutic potential that may be combined with immune checkpoint inhibitors (ICIs) to enhance systemic antitumor immunity. Its efficacy relies on the efficient and safe delivery of boron to cancer cells. This study evaluated the acute toxicity of a self-assembling peptide-based boron carrier composed of A6K and sodium borocaptate (BSH) at a 1:10 molar ratio (A6K/BSH boron drug), which had previously shown excellent tumor-selective accumulation and prolonged intracellular retention. Methods: A single-dose intraperitoneal toxicity study was performed in 6-week-old BALB/c mice (n = 6 per group; 3 males and 3 females). Animals received BSH-equivalent doses of 0, 30, 100, 300, or 600 mg/kg and were observed for 14 days. Mortality, clinical signs, body weight, gross necropsy findings, and histopathological characteristics of major organs were then assessed. Results: No mortality or treatment-related clinical signs were observed. Body weight changes were comparable between the control and treated groups. Gross necropsy revealed no treatment-related abnormalities. Histopathology showed mild hepatocellular hypertrophy and granular degeneration without dose dependency. No other organ toxicities or sex-related differences were detected. Conclusions: A single intraperitoneal administration of the A6K/BSH boron drug up to 600 mg/kg (BSH-equivalent) produced no evident acute systemic toxicity, suggesting that the approximate lethal dose exceeds 600 mg/kg for both sexes. This initial safety assessment supports the further development of the A6K/BSH boron drug as a boron delivery agent for BNCT. Further studies are needed to confirm its safety under clinically relevant conditions.