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.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
5.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
6.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
7.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
8.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
9.Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea
Sehyun JUNG ; Soojin LEE ; Yaerim KIM ; Semin CHO ; Hyuk HUH ; Yong Chul KIM ; Seung Seok HAN ; Hajeong LEE ; Jung Pyo LEE ; Kwon Wook JOO ; Chun Soo LIM ; Yon Su KIM ; Dong Ki KIM ; Kyungdo HAN ; Sehoon PARK
Kidney Research and Clinical Practice 2024;43(2):202-215
Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. Methods: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. Results: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90–120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. Conclusion: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.
10.Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study
Sehoon PARK ; Seong Geun KIM ; Soojin LEE ; Yaerim KIM ; Semin CHO ; Kwangsoo KIM ; Yong Chul KIM ; Seung Seok HAN ; Hajeong LEE ; Jung Pyo LEE ; Kwon Wook JOO ; Chun Soo LIM ; Yon Su KIM ; Dong Ki KIM
Kidney Research and Clinical Practice 2023;42(4):460-472
Background:
The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function.
Methods:
Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed.
Results:
Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated.
Conclusion
Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

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