Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Background: The Dejour classification is widely accepted for grading the severity of trochlear dysplasia. However, whether it serves as a reliable prognostic marker for patellar instability surgery or a guide for clinical decision-making has yet to be established. Medial patellofemoral ligament (MPFL) reconstruction, with or without tibial tubercle osteotomy (TTO), yields comparable outcomes across Dejour grades. Nonetheless, we hypothesized that specific trochlear parameters would be more significant predictors of surgical results. Methods: This study included patients who underwent MPFL reconstruction, with or without TTO, for recurrent patellar dislocation at a single institution between 2010 and 2023. Patients with at least 1 year of follow-up were included. Preoperative demographics, radiographic measurements such as sulcus angle, lateral trochlear inclination (LTI), and trochlear depth, patient-reported outcome measures (PROMs), and intraoperative findings including cartilage status were analyzed. Severe trochlear dysplasia (STD) was categorized as Dejour B/D, while non-STD encompassed all other cases, and these 2 groups were compared. Postoperative PROMs were assessed at 1 year postoperatively and at the final follow-up. A noninferiority test was performed using Kujala, Lysholm, and International Knee Documentation Committee (IKDC) scores, with the inferiority margin defined by the minimal clinically important difference (MCID). Linear relationships between LTI, a widely used indicator of trochleoplasty, and PROMs were evaluated. Additionally, differences in the proportion of patients achieving MCID, substantial clinical benefit, and patient-acceptable symptom state were analyzed using odds ratios. Results: Forty-two knees (41 patients) were finally enrolled. Radiographic measurements, except for LTI at the most proximal trochlea, showed no significant differences between the STD and non-STD groups. Clinical outcomes also demonstrated no significant differences between the 2 groups, and noninferiority was confirmed. When analyzed based on LTI, no differences in PROMs were observed at the postoperative 1 year. However, at the final follow-up (mean, 37.27 months), the most proximal trochlear LTI showed significant correlations with both Kujala and Knee Injury and Osteoarthritis Outcome Score over the follow-up period. Conclusions MPFL reconstruction, with or without TTO, leads to similar clinical improvements for STD classified by Dejour criteria. However, when assessed using proximal LTI, dysplasia’s role as a prognostic factor should be considered.

Purpose: This study aimed to evaluate and optimize microbial DNA extraction methods from urine, a non-invasive sample source, to enhance DNA quality, purity, and reliability for urinary microbiome research and biomarker discovery in bladder cancer. Materials and Methods: A total of 302 individuals (258 with genitourinary cancers and 44 with benign urologic diseases) participated in this study. Urine samples were collected via sterile catheterization, resulting in 445 vials for microbial analysis. DNA extraction was performed using three protocols: the standard protocol (SP), water dilution protocol (WDP), and chelation-assisted protocol (CAP). DNA quality (concentration, purity, and contamination levels) was assessed using NanoDrop spectrophotometry.Microbial analysis was conducted on 138 samples (108 cancerous and 30 benign) using 16S rRNA sequencing. Prior to sequencing on the Illumina MiSeq platform, Victor 3 fluorometry was used for validation. Results: WDP outperformed other methods, achieving significantly higher 260/280 and 260/230 ratios, indicating superior DNA purity and reduced contamination, while maintaining reliable DNA yields. CAP was excluded due to poor performance across all metrics. Microbial abundance was significantly higher in WDP-extracted samples (p<0.0001), whereas SP demonstrated higher alpha diversity indices (p<0.01), likely due to improved detection of low-abundance taxa. Beta diversity analysis showed no significant compositional differences between SP and WDP (p=1.0), supporting the reliability of WDP for microbiome research. Conclusions WDP is a highly effective and reliable method for microbial DNA extraction from urine, ensuring high-quality and reproducible results. Future research should address sample variability and crystal precipitation to further refine microbiome-based diagnostics and therapeutics.

The deregulation of protein translational machinery and the oncogenic role of several translation initiation factors have been extensively investigated. This study aimed to investigate the role of eukaryotic translation initiation factor 2S2 (eIF2S2, also known as eIF2β) in cervical carcinogenesis. Immunohistochemical analysis of human cervical carcinoma tissues revealed a stage-specific increase in eIF2S2 expression. The knockdown of eIF2S2 in human cervical cancer (SiHa) cells significantly reduced growth and migration properties, whereas its overexpression demonstrated the opposite effect. Immunoprecipitation and Bimolecular fluorescence complementation (BiFC) assay confirmed the previous photo array finding of the interaction between eIF2S2 and SMAD4 to understand the tumorigenic mechanism of eIF2S2. The results indicated that the N-terminus of eIF2S2 interacts with the MH-1 domain of SMAD4. The interaction effect between eIF2S2 and SMAD4 was further evaluated. The knockdown of eIF2S2 increased SMAD4 expression in cervical cancer cells without changing SMAD4 mRNA expression, whereas transient eIF2S2 overexpression reduced SMAD4 expression. This indicates the possibility of post-translational regulation of SMAD4 expression by eIF2S2. Additionally, eIF2S2 overexpression was confirmed to weaken the expression and/or promoter activity of p15 and p27, which are SMAD4-regulated antiproliferative proteins, by reducing SMAD4 levels. Therefore, our study indicated the pro-tumorigenic role of eIF2S2, which diminishes both SMAD4 expression and function as a transcriptional factor in cervical carcinogenesis.

The deregulation of protein translational machinery and the oncogenic role of several translation initiation factors have been extensively investigated. This study aimed to investigate the role of eukaryotic translation initiation factor 2S2 (eIF2S2, also known as eIF2β) in cervical carcinogenesis. Immunohistochemical analysis of human cervical carcinoma tissues revealed a stage-specific increase in eIF2S2 expression. The knockdown of eIF2S2 in human cervical cancer (SiHa) cells significantly reduced growth and migration properties, whereas its overexpression demonstrated the opposite effect. Immunoprecipitation and Bimolecular fluorescence complementation (BiFC) assay confirmed the previous photo array finding of the interaction between eIF2S2 and SMAD4 to understand the tumorigenic mechanism of eIF2S2. The results indicated that the N-terminus of eIF2S2 interacts with the MH-1 domain of SMAD4. The interaction effect between eIF2S2 and SMAD4 was further evaluated. The knockdown of eIF2S2 increased SMAD4 expression in cervical cancer cells without changing SMAD4 mRNA expression, whereas transient eIF2S2 overexpression reduced SMAD4 expression. This indicates the possibility of post-translational regulation of SMAD4 expression by eIF2S2. Additionally, eIF2S2 overexpression was confirmed to weaken the expression and/or promoter activity of p15 and p27, which are SMAD4-regulated antiproliferative proteins, by reducing SMAD4 levels. Therefore, our study indicated the pro-tumorigenic role of eIF2S2, which diminishes both SMAD4 expression and function as a transcriptional factor in cervical carcinogenesis.

Purpose: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of collagen type VI alpha 1 (COL6A1), a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC. Materials and Methods: Samples from 298 BC patients were subjected to RNA sequencing and real-time polymerase chain reaction. Results: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1, which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan–Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283–86.095; p=0.001 and p=0.0002 [log-rank test]). Conclusions These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions.

Live-born cases of partial trisomy 12q are rare, and only a few fetuses with this unbalanced translocation have survived to term. To our knowledge, only about 40 patients have been reported as having 12q duplication, and among them are no Korean reports. Here, we report the first Korean case of siblings with a 12q24.22q24.33 duplication. An 11-year-old boy visited our clinic for short stature. He was born small for his gestational age and had distinctive facial features, a history of surgery for anorectal malformation, psychomotor delay, intellectual disabilities, and attention-deficit/hyperactivity disorder (ADHD). He had an older sister with similar clinical features. The chromosomal microarray of the patient and his sister showed identical results: a 16.2 Mb duplication of 12q24.22q24.33. They had an identical cutoff point, but their symptoms were not. Symptoms common to both included growth retardation, psychomotor delay, intellectual disability, ADHD, and small for their gestational age.

Background: In a previous study, rhinoplasty rasp was shown an effective method for removal of button osteoma (BO) of the skull. Objective: In the present study, our experience was presented and surgical outcome using high-speed burr in surgery for BO evaluated. Methods: The register-based surgery reports of patients who underwent local excision of BO (2010∼2023) at a single institution were reviewed. Demographics, photodocumentation, radiologic examinations, pathology reports, data of scar prevention, and surgical outcome in the BO study cohort were analyzed. Results: A total of 20 BO lesions in 18 patients (14 females and four males; mean age of 52.4±14.3 years) who underwent surgery using high-speed burr were assessed. The mean size of BO was 9.3 mm (range, 5∼17 mm).Most of the BOs were located on the forehead (19/20, 95.0%), which was associated with the course of the supratrochlear (n=13) or supraorbital nerve (n=6). Minimal hematoma was complicated in three patients (16.7%).Delayed complications, recurrence, and severe scarring during the mean follow-up of 3.1±3.5 months were not reported. Conclusion The use of high-speed burr for surface smoothening may provide good surgical results in minimally invasive BO surgery.

The deregulation of protein translational machinery and the oncogenic role of several translation initiation factors have been extensively investigated. This study aimed to investigate the role of eukaryotic translation initiation factor 2S2 (eIF2S2, also known as eIF2β) in cervical carcinogenesis. Immunohistochemical analysis of human cervical carcinoma tissues revealed a stage-specific increase in eIF2S2 expression. The knockdown of eIF2S2 in human cervical cancer (SiHa) cells significantly reduced growth and migration properties, whereas its overexpression demonstrated the opposite effect. Immunoprecipitation and Bimolecular fluorescence complementation (BiFC) assay confirmed the previous photo array finding of the interaction between eIF2S2 and SMAD4 to understand the tumorigenic mechanism of eIF2S2. The results indicated that the N-terminus of eIF2S2 interacts with the MH-1 domain of SMAD4. The interaction effect between eIF2S2 and SMAD4 was further evaluated. The knockdown of eIF2S2 increased SMAD4 expression in cervical cancer cells without changing SMAD4 mRNA expression, whereas transient eIF2S2 overexpression reduced SMAD4 expression. This indicates the possibility of post-translational regulation of SMAD4 expression by eIF2S2. Additionally, eIF2S2 overexpression was confirmed to weaken the expression and/or promoter activity of p15 and p27, which are SMAD4-regulated antiproliferative proteins, by reducing SMAD4 levels. Therefore, our study indicated the pro-tumorigenic role of eIF2S2, which diminishes both SMAD4 expression and function as a transcriptional factor in cervical carcinogenesis.

Purpose: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. Materials and Methods: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. Results: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). Conclusion Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.