Background: Isocitrate dehydrogenase (IDH) wild-type (wt) glioblastoma is an aggressive malignancy associated with poor clinical outcomes, marked by high heterogeneity and resistance to treatment. This study aims to investigate the prognostic significance of B7-H3 expression in IDH wt glioblastoma and its potential association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS). Additionally, the relationship between B7-H3 and PD-L1 expression was explored. Methods: A retrospective cohort of 86 IDH wt glioblastoma patients, all of whom underwent surgery, radiotherapy, and temozolomide treatment, was analyzed. B7-H3 expression was quantified using an immunoreactivity score (IRS), classifying samples as low (IRS ≤ 4) or high (IRS > 4). PD-L1 expression was evaluated based on tumor and immune cell staining, with >5% positivity indicating significant expression. Results: High B7-H3 expression was significantly associated with poorer OS and PFS. Co-expression of B7-H3 and PD-L1 was prevalent, particularly among younger male patients with unifocal tumors; however, PD-L1 expression did not show a significant correlation with clinical outcomes. Conclusions: B7-H3 appears to be a promising prognostic biomarker in IDH wt glioblastoma and may serve as a target for developing combination therapies, integrating B7-H3-targeting treatments with immune checkpoint inhibitors. Further prospective studies are necessary to validate these findings and to explore potential therapeutic strategies.
This study aimed to evaluate the prognostic and predictive significance of Claudin-6 and trophoblast cell surface antigen-2 (Trop-2) expression in serous ovarian carcinoma, assessing their influence on treatment efficacy and clinical outcomes. A retrospective cohort of 73 patients diagnosed with serous ovarian carcinoma was analyzed. All patients underwent standard cytoreductive surgery, with or without neoadjuvant or adjuvant chemotherapy. Immunohistochemistry was used to assess the expression levels of Claudin-6 and Trop-2. Survival outcomes were evaluated using Kaplan–Meier and Cox proportional hazards models, with overall survival (OS) as the primary endpoint. High Trop-2 expression was observed in 67.1% of the patients, while 46.6% exhibited high Claudin-6 expression. Both markers were more common in older, postmenopausal patients, those with larger tumors, and those with distant metastasis. However, no significant associations were found with clinical factors (P > .05). Survival analysis demonstrated that high Trop-2 and Claudin-6 expression were associated with shorter OS and progression-free survival (PFS). Patients with high Trop-2 expression exhibited a median OS of 38 months and PFS of 32 months, whereas those with low Trop-2 expression had a median OS of 62 months and PFS of 60 months (OS: P = .039, PFS: P = .020). Similarly, high Claudin-6 expression was associated with a median OS of 32 months and PFS of 21 months, compared to an OS of 60 months and PFS of 56 months in patients with low Claudin-6 expression (OS: P = .005, PFS: P = .003). Both univariate and multivariate analyses confirmed that advanced age, and high Trop-2, and high Claudin-6 expression were significant predictors of poor OS and PFS (P < .05). These findings underscore the prognostic significance of Claudin-6 and Trop-2 in ovarian cancer, with elevated expression correlating with poorer survival outcomes. These markers may serve as independent prognostic factors, and their targeting through antibody–drug conjugates offers a potential therapeutic strategy to improve survival outcomes and overcome treatment resistance.
Although many studies have been conducted to explore the relationship between mast cells (MC) and angiogenesis, comparison of this relationship with tumor necrosis has not been investigated to the best of our knowledge. Therefore, the relationship between MC and neovascularization in stomach,...
Isthmin-1 (ISM-1) is a multifunctional secreted protein expressed in various tissues, exhibiting biological activities that overlap with mast cell functions. To date, no study has demonstrated its expression in mast cells. This study presents the first evidence of ISM-1 immunoreactivity in mast cells and investigates its diagnostic relevance in cutaneous mastocytosis. Thirty-nine patients diagnosed with cutaneous mastocytosis from 2 tertiary centers were retrospectively evaluated. Formalin-fixed paraffin-embedded skin biopsy specimens were immunohistochemically stained using antibodies against ISM-1 and CD117. Expression levels were semiquantitatively scored, and associations with clinical, histopathological, and demographic variables were statistically analyzed. All cases exhibited ISM-1 positivity, with 69.2% demonstrating high expression. Notably, ISM-1 remained highly expressed in 2 cases with low CD117 immunoreactivity. While ISM-1 showed diagnostic sensitivity and specificity comparable to CD117, its distinct nuclear localization provided enhanced morphological clarity for mast cell identification. Cases with high ISM-1 expression showed increased eosinophil counts; however, this trend did not reach statistical significance. These findings suggest that ISM-1 may serve as a complementary immunohistochemical marker for mast cell detection, particularly in diagnostically challenging cases. Moreover, its nuclear staining introduces a novel morphological feature that may improve histopathological assessment of mastocytosis and warrants further investigation in mast cell-associated disorders.
17 March 2025 in Archives of Dermatological Research
Background and Objectives: Prostate cancer exhibits substantial biological heterogeneity. Although several biomarkers reflecting aggressive tumor behavior have been identified, molecular indicators related to biological adaptation to androgen deprivation remain limited. This study aimed to comparatively evaluate ISM-1 and B7-H3 expression in localized prostate cancer (LPC) and the pre-CRPC group (pre-treatment diagnostic biopsy tissue from patients who subsequently developed CRPC), and to investigate their clinicopathological associations in the pre-CRPC group. Materials and Methods: This retrospective study included 30 surgically treated LPC cases and 32 pre-CRPC cases with available prostate tissue samples obtained prior to the development of castration resistance. ISM-1 and B7-H3 expression levels were evaluated immunohistochemically using the H-score method (intensity 0–3 × proportion score 0–3 [0%, 1–19%, 20–50%, >50%]). Expression patterns were compared between LPC and pre-CRPC groups. Within the pre-CRPC group, associations with clinicopathological parameters were evaluated using H-scores as continuous variables, and time to castration resistance was analyzed using Cox regression. Results: ISM-1 expression was generally low in LPC cases, with a median H-score of 0, whereas pre-CRPC biopsy tissues demonstrated a marked increase in ISM-1 expression. B7-H3 expression was higher and more homogeneous in the pre-CRPC group compared with LPC. In the pre-CRPC group, ISM-1 and B7-H3 H-scores showed a strong positive correlation. No statistically significant associations were identified between ISM-1 or B7-H3 expression levels and most conventional clinicopathological parameters; however, both markers differed significantly across Grade Groups. Neither marker showed a statistically significant association with time to castration resistance, although ISM-1 demonstrated a non-significant trend toward a longer time to resistance. Conclusions: ISM-1 and B7-H3 exhibit distinct expression patterns across different stages of prostate cancer but show associated expression profiles in the pre-CRPC group. While B7-H3 appears to reflect aggressive tumor biology, the independent expression pattern of ISM-1 and its non-significant trend toward a longer time to resistance suggest a potential role in the clinical trajectory toward castration resistance. Combined assessment of ISM-1 and B7-H3 may contribute to a better understanding of tumor biology in patients who subsequently develop CRPC. These findings are descriptive and hypothesis-generating.