Hoon Kyu Oh

Background: Digital cytopathology (DC) is emerging as a transformative approach in quality assurance programs (QAP), though its comprehensive evaluation remains limited. Since 2020, the Korean Society for Cytopathology has progressively incorporated DC into its national QAP, including digital proficiency testing (PT), sample adequacy testing (SAT), a customizable PT module, and a self-assessment module (SAM), aiming for full digital implementation by 2026. Methods: This 5-year study assessed diagnostic concordance between conventional and digital PT formats and analyzed participant feedback on service quality and digital image usability across PT, SAT, and SAM. Parallel testing was conducted during the transitional phase, and satisfaction was measured through structured surveys. Results: Participation in digital PT increased from 48 institutions in 2020 to 93 in 2024, while digital SAT participation rose from 29 to 71 between 2022 and 2024. In 2023, 56 institutions joined SAM. Diagnostic concordance rates were comparable between digital and conventional PTs (78.6%–84.6% vs. 82.0%–85.1%), including similar category C (major discordance) rates. Satisfaction with digital PT services and image quality exceeded 85%, and over 90% of institutions reported positive feedback on SAT and SAM. Over 80% were satisfied with the customizable PT module. Conclusions: DC is a reliable and effective modality for cytopathology QAP. It demonstrates diagnostic equivalence to conventional methods and high user satisfaction, supporting its broader implementation in national quality assurance frameworks.

Background: The Korean Society for Cytopathology introduced a digital proficiency test (PT) in 2021. However, many doubtful opinions remain on whether digitally scanned images can satisfactorily present subtle differences in the nuclear features and chromatin patterns of cytological samples.Methods: We prepared 30 whole-slide images (WSIs) from the conventional PT archive by a selection process for digital PT. Digital and conventional PT were performed in parallel for volunteer institutes, and the results were compared using feedback. To assess the quality of cytological assessment WSIs, 12 slides were collected and scanned using five different scanners, with four cytopathologists evaluating image quality through a questionnaire.Results: Among the 215 institutes, 108 and 107 participated in glass and digital PT, respectively. No significant difference was noted in category C (major discordance), although the number of discordant cases was slightly higher in the digital PT group. Leica, 3DHistech Pannoramic 250 Flash, and Hamamatsu NanoZoomer 360 systems showed comparable results in terms of image quality, feature presentation, and error rates for most cytological samples. Overall satisfaction was observed with the general convenience and image quality of digital PT.Conclusions: As three-dimensional clusters are common and nuclear/chromatin features are critical for cytological interpretation, careful selection of scanners and optimal conditions are mandatory for the successful establishment of digital quality assurance programs in cytology.

(1) Background: Ultrasound (US) elastography is an imaging technology that reveals tissue stiffness. This study aimed to investigate whether fibrotic focus (FF) affects elastographic findings in breast cancer, and to evaluate the clinical significance of US elastography and FF in breast cancer. (2) Methods: In this study, 151 patients with breast cancer who underwent surgery were included. Strain elastography was performed and an elasticity scoring system was used to assess the findings. The elasticity scores were classified as negative, equivocal, or positive. FF was evaluated in the surgical specimens. Medical records were reviewed for all patients. (3) Results: Elastographic findings were equivocal in 30 patients (19.9%) and positive in 121 patients (80.1%). FF was present in 68 patients (46.9%). There was no correlation between elastographic findings and FF. Older age, larger tumor size, lymph node metastasis, and higher tumor stage were associated with positive elastographic results. FF showed a positive correlation with age, postmenopausal status, tumor size, lymphovascular invasion, lymph node metastasis, tumor stage, and intratumoral and peritumoral inflammation. (4) Conclusions: Our study showed that positive elastographic results and FF were associated with poor prognostic factors for breast cancer. FF did not affect the elastographic findings of this study.

Original Article Tumor-treating fields in combination with sorafenib curtails the growth of colorectal carcinoma by inactivating AKT/STAT3 signaling Eun Ho Kim, Won Seok Lee, Hoon-Kyu Oh

Objective: This study aimed to investigate the neural elements of the subacromial bursa (SAB) in rotator cuff tears. Materials and methods: Twenty patients with rotator cuff tears were recruited, and their visual analog scale (VAS) score, duration of symptoms, and range of motion (ROM), including flexion, external rotation, and internal rotation were evaluated. Tear size was measured using magnetic resonance imaging (MRI). The SAB specimens obtained during arthroscopic rotator cuff repair were studied using routine hematoxylin and eosin staining and immunohistochemistry (S-100 protein and PGP 9.5 protein). The SAB specimen for the control group was obtained from 2 fresh cadavers and 2 patients with acute humeral shaft fracture. The Mann-Whitney U test was applied to assess the difference between histological findings of the rotator cuff tear group and control group. The correlation between the histological findings and clinical features was evaluated using the Spearman correlation coefficient. Results: The mean duration of symptom was 10.2 ± 6.4 months. The preoperative average VAS score was 2.9 ± 1.2. The degrees of preoperative ROM in forward flexion and external and internal rotations were 143.8 ± 19.5, 49.5 ± 23.1, and –4.3 ± 4.2, respectively. The tear was 2.0 ± 0.9 cm. For histological findings, the number of neural elements per low power field in the rotator cuff tear group was significantly less than the control group in both immunohistochemical stainings (S-100: 0.5 ± 0.7 vs 2.8 ± 0.5, p < .01; PGP 9.5: 0.4 ± 0.7 vs 3.5 ± 0.6, p < .01). During the correlation analysis, the number of neural elements in the PGP 9.5 staining was negatively correlated with the ROM in forward flexion and external rotation. Conclusion: This study revealed that chronic rotator cuff tears may induce degeneration of neural elements in SAB.

Cluster of differentiation (CD) 73, which is encoded by the NT5E gene, regulates production of immunosuppressive adenosine and is an emerging checkpoint in cancer immunotherapy. Despite the significance of CD73 in immuno-oncology, the roles of the NT5E gene methylation in breast cancer have not been well-defined yet. Therefore, we aimed to investigate the prognostic significance of the NT5E gene methylation in breast cancer. The DNA methylation status of the NT5E gene was analyzed using pyrosequencing in breast cancer tissues. In addition, the levels of inflammatory markers and lymphocyte infiltration were evaluated. The mean methylation level of the NT5E gene was significantly higher in breast cancer than in normal breast tissues. In the analysis of relevance with clinicopathologic characteristics, the mean methylation levels of the NT5E gene were significantly higher in patients with large tumor size, high histologic grade, negative estrogen receptor expression, negative Bcl-2 expression, and premenopausal women. There was no difference in disease-free survival according to the methylation status of the NT5E gene. We found that the NT5E gene methylation was related to breast cancer development and associated with poor prognostic factors in breast cancer. Our results suggest that the NT5E gene methylation has potential as an epigenetic biomarker in breast cancer.

The Korean Society for Cytopathology has conducted the Continuous Quality Improvement program for cytopathology laboratories in Korea since 1995. In 2018 as part of the program, an annual survey of cytologic data was administered to determine the current status of cytopathology practices in Korea. A questionnaire was administered to 211 cytopathology laboratories. Individual laboratories submitted their annual statistics regarding cytopathology practices, diagnoses of gynecologic samples, inadequacy rates, and gynecologic cytology-histology correlation review (CHCR) data for 2018. In addition, proficiency tests and sample adequacy assessments were conducted using five consequent gynecologic slides. Over 10 million cytologic exams were performed in 2018, and this number has almost tripled since this survey was first conducted in 2004 (compounded annual growth rate of 7.2%). The number of non-gynecologic samples has increased gradually over time and comprised 24% of all exams. The overall unsatisfactory rate was 0.14%. The ratio of the cases with atypical squamous cells to squamous intraepithelial lesions accounted for up to 4.24. The major discrepancy rate of the CHCR in gynecologic samples was 0.52%. In the proficiency test, the major discrepancy rate was approximately 1%. In the sample adequacy assessment, a discrepancy was observed in 0.1% of cases. This study represents the current status of cytopathology practices in Korea, illustrating the importance of the Continuous Quality Improvement program for increasing the accuracy and credibility of cytopathologic exams as well as developing national cancer exam guidelines and government projects on the prevention and treatment of cancer.

Since 1995, the Korean Society for Cytopathology has overseen the Continuous Quality Improvement program for cytopathology laboratories. The Committee of Quality Improvement has carried out an annual survey of cytology data for each laboratory and set standards for proficiency tests. Evaluations were conducted four times per year from 2008 to 2018 and comprised statistics regarding cytology diagnoses of previous years, proficiency tests using cytology slides provided by the committee, assessment of adequacy of gynecology (GYN) cytology slides, and submission of cytology slides for proficiency tests. A total of 206 institutes participated in 2017, and the results were as follows. The number of cytology tests increased from year to year. The ratio of liquid-based cytology in GYN gradually decreased, as most of the GYN cytology had been performed at commercial laboratories. The distribution of GYN diagnoses demonstrated nearly 3.0% as atypical squamous cells. The rate for squamous cell carcinoma was less than 0.02%. The atypical squamous cell/squamous intraepithelial lesion ratio was about 3:1 and showed an upward trend. The major discordant rate of cytology-histology in GYN cytology was less than 1%. The proficiency test maintained a major discordant rate less than 2%. The rate of inappropriate specimens for GYN cytology slides gradually decreased. The Continuous Quality Improvement program should be included in quality assurance programs. Moreover, these data can contribute to development of national cancer examination guidelines and facilitate cancer prevention and treatment.

A newly diagnosed or recurrent Glioblastoma multiforme (GBM) can be treated with Tumor-treating fields (TTFields), an emerging type of alternative electric field-based therapy using low-intensity electric fields. TTFields have a penchant to arrest mitosis, eventually leadingto apoptosis. Therefore, it is regarded as a potential anticancer therapy. However, in this study, we confirmed the combined efficacy of sorafenib and TTFields to improve the treatment efficiency of malignant GBM. Experimentation revealed the ability of sorafenib to decrease the signal transducer and activator of transcription 3 (STAT3) and this inhibition increased the sensitivity of TTFields in preventing tumor expansion. It was found that both combinatorial as well as monotherapy aimed to inhibit or reduce the level of STAT3, but the extent was different and based upon the reaction conditions. This drug is also capable of arresting multiple kinase pathways along with STAT3-related proteins (Mcl-1 and Survivin). STAT3 silencing can also be accomplished by RNA interference and can increase the TTFields-sensitizing effect of sorafenib. If the effects are reversed and gene regulating STAT3 is expressed more, it annihilates the effects of treatment. Moreover, sorafenib plus TTFields significantly inhibited xenograft tumor growth and combinatorial treatment reduced STAT3 expression more effectively in vivo. These in vitro and in vivo results indicate that sorafenib tends to sensitize GBM cells to TTFields-induced apoptosis by inhibiting STAT3.

The nuclear factor (NF)-κB family of transcriptional factors plays a critical role in inflammation, immunoregulation, cell differentiation, and tumorigenesis. This study aims to investigate the role of methylation of genes encoding for the NF-κB family in breast cancer. We analyze the DNA methylation status of the NFKB1 gene and the RELA gene in breast cancer using pyrosequencing. The expression of NF-κB1 and RELA proteins is assessed and the level of RNA transcripts in frozen tissue is determined using RT-PCR. There is no statistically significant difference in the methylation status of the NFKB1 and the RELA genes between tumors and normal tissues. The methylation status of the NFKB1 gene and the RELA gene is not significantly associated with the levels of NF-κB1 transcripts in tumor tissues. However, the methylation level of the RELA gene is significantly associated with the level of tumor necrosis factor (TNF)-α. In addition, the level of NF-κB1 transcripts was associated with the levels of TNF-α and IL-4. In tumors with positive TNF-α, the increased methylation level of the RELA gene is significantly associated with the positive expression of NF-κB1 transcripts. These results demonstrate that the level of the RELA gene methylation is related to the levels of NF-κB1 transcripts under the influence of TNF-α. Further study is needed to determine how TNF-α is involved in the methylation of the RELA gene and the subsequent expression of NF-κB1.