1.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
2.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
3.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
4.Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer
Il-Hyun PARK ; Dae-Soon SON ; Yoon-La CHOI ; Ji-Hyeon CHOI ; Ji-Eun PARK ; Yeong Jeong JEON ; Minseob CHO ; Hong Kwan KIM ; Yong Soo CHOI ; Young Mog SHIM ; Jung Hee KANG ; Suzy PARK ; Jinseon LEE ; Sung-Hyun KIM ; Byung-Chul LEE ; Jhingook KIM
Cancer Research and Treatment 2024;56(1):81-91
Purpose:
Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens.
Materials and Methods:
In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee.
Results:
The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients.
Conclusion
The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.
5.Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea
Hee Jeong LEE ; Iksung CHO ; Dae-Young KIM ; Jang-Won SON ; Kang-Un CHOI ; Seonhwa LEE ; In-Cheol KIM ; Kyu-Yong KO ; Kyung Eun HA ; Seo-Yeon GWAK ; Kyu KIM ; Jiwon SEO ; Hojeong KIM ; Chi Young SHIM ; Jong-Won HA ; Hyungseop KIM ; Geu-Ru HONG ; Jagat NARULA
Journal of Korean Medical Science 2024;39(17):e152-
Background:
The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth.
Methods:
From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed.
Results:
Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6–73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy.
Conclusion
This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.
6.Hepatocellular carcinoma incidence is decreasing in Korea but increasing in the very elderly
Young Eun CHON ; Seong Yong PARK ; Han Pyo HONG ; Donghee SON ; Jonghyun LEE ; Eileen YOON ; Soon Sun KIM ; Sang Bong AHN ; Soung Won JEONG ; Dae Won JUN
Clinical and Molecular Hepatology 2023;29(1):120-134
Background/Aims:
A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028.
Methods:
Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC.
Results:
The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028.
Conclusions
The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.
7.Survey on the Status of Breastfeeding in Korean Medical Institution Workers
Tae Hyeong KIM ; Sung-Hoon CHUNG ; Jun Hwan KIM ; Youngmin AHN ; Son Moon SHIN ; Woo Ryoung LEE ; Eui Kyung CHOI ; Juyoung LEE ; Hye-Jung SHIN ; Euiseok JUNG ; Ju Sun HEO ; Jin A LEE ; Soon Min LEE ; Seong Phil BAE ; Jeonglyn SONG ; Chae-Young KIM ; Dae Yong YI
Journal of Korean Medical Science 2022;37(15):e120-
Background:
Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers.
Methods:
A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded.
Results:
Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances.
Conclusion
In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.
8.Differences in Clinical Responses to Ustekinumab Treatment among Body Regions: Results from a Real-World Prospective, Observational, and Multi-Center Study in Korea
Sang Wook SON ; Dae Young YU ; Youngdoe KIM ; Hyo Hyun AHN ; Yong Hyun JANG ; Joo Young ROH ; Young Bok LEE ; Ji Yeoun LEE ; Myung Hwa KIM ; YoungJa LEE ; Gyeong-Hun PARK ; Hyun-Sun YOON ; Sang Woong YOUN ;
Annals of Dermatology 2022;34(1):14-21
Background:
In psoriasis treatment, not all body regions improve simultaneously after clinical interventions.
Objective:
This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans.
Methods:
This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis.
Results:
The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits.
Conclusion
We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment.
9.2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon HUR ; Min Kyong MOON ; Jong Suk PARK ; Soo-Kyung KIM ; Seung-Hwan LEE ; Jae-Seung YUN ; Jong Ha BAEK ; Junghyun NOH ; Byung-Wan LEE ; Tae Jung OH ; Suk CHON ; Ye Seul YANG ; Jang Won SON ; Jong Han CHOI ; Kee Ho SONG ; Nam Hoon KIM ; Sang Yong KIM ; Jin Wha KIM ; Sang Youl RHEE ; You-Bin LEE ; Sang-Man JIN ; Jae Hyeon KIM ; Chong Hwa KIM ; Dae Jung KIM ; SungWan CHUN ; Eun-Jung RHEE ; Hyun Min KIM ; Hyun Jung KIM ; Donghyun JEE ; Jae Hyun KIM ; Won Seok CHOI ; Eun-Young LEE ; Kun-Ho YOON ; Seung-Hyun KO ;
Diabetes & Metabolism Journal 2021;45(4):461-481
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
10.Inflammatory responses of C57BL/6NKorl mice to dextran sulfate sodium-induced colitis: comparison between three C57BL/6N sub-strains
Sou Hyun KIM ; Doyoung KWON ; Seung Won SON ; Tae Bin JEONG ; Seunghyun LEE ; Jae-Hwan KWAK ; Joon-Yong CHO ; Dae Youn HWANG ; Min-Soo SEO ; Kil Soo KIM ; Young-Suk JUNG
Laboratory Animal Research 2021;37(1):67-73
Background:
Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model.
Results:
Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains.
Conclusions
These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

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