This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

Objective: To investigate whether breast tissue composition on preoperative automated breast ultrasound (ABUS) is associated with the accuracy of cancer multiplicity evaluation and postoperative recurrence-free survival (RFS) in patients with early-stage breast cancer. Materials and Methods: This retrospective analysis included women with early-stage breast cancer (clinical Tis, T1–2/N0) who underwent ABUS and digital mammography (DM) between October 2019 and April 2021. Tissue composition on ABUS was assessed using the Breast Imaging Reporting and Data System background echotexture (BE) (homogeneous-fat, homogeneous-fibroglandular, or heterogeneous). In a subgroup of patients with mammographically dense breasts, the glandular tissue component (GTC) on ABUS were further stratified into high (moderate or marked) or low (minimal or mild).Multivariable logistic and Cox regression analyses were used to identify factors associated with accurate cancer multiplicity categorization (unifocal, multifocal/multicentric, or bilateral) using ABUS + DM, and with RFS, respectively. Results: Among 409 women (mean age ± standard deviation, 50.2 ± 8.7 years), ABUS combined with DM yielded accurate cancer multiplicity categorization in 368 patients (90.0%). Neither BE nor GTC on ABUS affected the accuracy of categorization when ABUS was combined with DM. Over a median postoperative follow-up of 3.5 years, 11 recurrences occurred. Heterogeneous BE on ABUS (hazard ratio [HR] 11.24 [95% confidence interval [CI]: 2.82–44.92]; P = 0.001), BRCA mutation (HR 15.94 [2.47–102.97]; P = 0.004), and pathologic index cancer size (HR per 1-cm increase 1.91 [1.13–3.23];P = 0.02) was independently associated with RFS. In patients with dense breasts, heterogeneous BE (HR 14.17 [95% CI:2.69–74.60]; P = 0.002) and high GTC (HR 10.32 [2.35–45.28]; P = 0.002) on ABUS, BRCA mutation (HR 24.34 [2.75– 215.06]; P = 0.004), and pathologic cancer size (HR per 1-cm increase 2.62 [1.50–4.59]; P = 0.001) was independently associated with RFS. Conclusion In patients with early-stage breast cancer, heterogeneous BE and high GTC on preoperative ABUS, along with larger cancer size and BRCA mutation, was associated with worse RFS. However, BE and GTC did not affect cancer multiplicity evaluation when ABUS was used in combination with DM.

Objective: To evaluate the performance of supplemental automated breast ultrasound (ABUS) added to mammography-based breast cancer screening for women with nondense breasts. Materials and Methods: A retrospective search of radiology databases at two tertiary institutions identified asymptomatic women with nondense breasts who underwent breast cancer screening using both digital mammography (DM) and supplemental ABUS between January 2020 and December 2023. We excluded women without sufficient follow-up data or those without an established final diagnosis, including histopathologic results. The performance measures of DM alone and ABUS combined with DM (ABUS plus DM) were compared. The primary outcome was the cancer detection rate (CDR), and the secondary outcomes were sensitivity and specificity. Subgroup analyses were performed for women with scattered fibroglandular density and almost entirely fatty breasts. Results: A total of 2,904 pairs of screening examinations were performed in 1,683 women (59 ± 10 years), detecting 26 cancers. In comparison with DM alone, ABUS plus DM showed higher CDR (9.0 vs. 7.9 per 1,000 examinations, P < 0.001), higher sensitivity (100% [26/26] vs. 88.5% [23/26], P < 0.001), and lower specificity (95.0% [2,735/2,878] vs. 97.9% [2,817/2,878], P < 0.001). In women with scattered fibroglandular density, ABUS increased the CDR from 7.4 to 8.5 per 1,000 examinations and improved the sensitivity from 87.0% [20/23] to 100% [23/23] (P < 0.001). In women with almost entirely fatty breasts, ABUS plus DM showed the same CDR (16.4 per 1,000 examinations) and sensitivity (100% [3/3]) as DM alone. Three cancers (11.5% [3/26]), all of which were stage T1N0, were detected only by supplemental ABUS. Conclusion Supplemental ABUS improved cancer detection and sensitivity in women with nondense breasts, with the benefits primarily observed in those with scattered fibroglandular density.

Autophagy is a conserved catabolic process that degrades proteins and damaged organelles to maintain cellular homeostasis, and its role in cancer depends on stage and context. Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) is an essential enzyme in the sterol branch of the mevalonate pathway, but its functions in hepatocellular carcinoma (HCC) and in the regulation of autophagy remain poorly understood. In this study, we show that FDFT1 acts as a negative regulator of autophagy in HCC cells. Loss of FDFT1 led to increased autophagosome formation and fusion with lysosomes, whereas its overexpression suppressed both basal and induced autophagy. These changes were associated with AMPK–ULK1 signaling, suggesting that FDFT1 influences a central pathway controlling autophagy. Our findings connect cholesterol metabolism with autophagy regulation and tumor growth, highlighting FDFT1 as a potential prognostic marker and therapeutic target in liver cancer.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Pediatric kidney disease has a relatively lower prevalence than do other pediatric conditions and has a notably different etiology from kidney diseases observed in adults. Furthermore, the pediatric population is unique in that they experience ongoing growth and development, distinguishing them from adult patients. Consequently, pediatric patients with kidney disease require more specialized and meticulous nutritional management than do adults. To address this need and promote optimal dietary practices for pediatric patients with kidney disease, pediatric nephrologists from the Korean Society of Pediatric Nephrology and nutritionists from the Korean Society of Clinical Nutrition have collaborated to establish nutritional guidelines specifically tailored to Korean dietary patterns. These guidelines offer detailed, nutrient-specific recommendations covering energy, protein, calcium, phosphorus, and potassium consumption while providing practical, culturally relevant guidance intended to support both pediatric patients and their caregivers.

Myofibromas are rare mesenchymal neoplasms that primarily affect infants and young children, most commonly arising in the skin, subcutaneous tissue, muscle, or bone. These tumors present with a broad clinical spectrum, ranging from self-limiting lesions to disseminated and fatal cases. In adults, the solitary form is encountered more frequently than the multicentric type. Although myofibromas may occur in the oral region of the head and neck, isolated cases involving the nasal septum are exceedingly rare. Here, we describe a case of solitary adult-onset myofibroma of the nasal septum that was successfully excised through transnasal endoscopic surgery.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.