• Journal of Gastric Cancer
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• 제6권4호
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• pp.277-283
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• 2006

목적: 위암환자에서 위절제술 시행 시 절제연거리가 종양의 특성에 따라 재발률, 재발양상 및 예후에 어떠한 영향을 미치는지 명확히 알려져 있지 않다. 연구자들은 이런 관점에서 분석하여 보다 적극적인 치료가 필요한 대상환자를 선별하여 맞춤치료의 기준을 찾고자 한다. 대상 및 방법: 본원에서 1992년 6월부터 2005년 12월까지 위암으로 위절제술을 시행 받은 환자 중 절제연 암침윤 음성이었던 4,472명을 대상으로 후향적 연구를 시행하였다. 추적기간 중앙값은 37개월($1{\sim}162$개월)이었다. 결과: 조기위암 환자군에서 절제연거리가 2 cm 미만인 군과 이상인 군 사이에 재발률, 재발양상 및 5년 생존율에 차이가 없었다. 진행위암 환자는 절제연거리 3 cm를 기준으로 분류하였을 때 그 이상인 경우와 미만인 환자군의 생존율에 의미있는 차이가 있었다(P=0.02). 진행위암 환자 중 미만형, 위하부 1/3 위암, Borrmann 3, 4형은 절제연거리가 3 cm 이상인 군이 미만인 군에 비해 생존율의 의미 있는 차이를 보였다(P<0.05). 생존율에 영향을 미치는 인자는 다변량 생존분석 결과 연령, 병기, 수술방법, Borrmann형, 근치도가 독립적인 인자였다. 결론: 위암환자에서 위절제술 시행 시 종양의 변연부와 근위부 위절제연까지의 거리는 조기위암의 경우 재발률 및 생존율에 영향을 미치는 의미 있는 인자로 생각되지 않으며, 진행위암은 미만형, 하부 1/3, Borrmann 3, 4형의 경우에는 절제연을 3 cm 이상 확보하는 것이 환자의 생존율 향상에 중요할 것으로 판단된다.

• Journal of Gastric Cancer
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• 제20권4호
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• pp.408-420
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• 2020

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively). Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions: CLDN18.2 expression was reduced in patients with PM but significantly intact in those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

• Journal of Gastric Cancer
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• 제1권4호
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• pp.202-209
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• 2001

Purpose: When cancer cels invade the stroma, they should be dissociated from the adjacent cells at first. E-cadherin and $\beta-catenin$ constitute an important protein complex associated with cellular adhesion, development, and differentiation, especially in epithelial cells. The role of E-cadherin and $\beta-catenin$ in gastric carcinogenesis were studied. Materials and Methods: The expression of E-cadherin and $\beta-catenin$ in gastric adenocarcinomas by using immunohistochemical staining and the mutation by using polymerase chain reaction- single stranded conformation polymorphism (PCR-SSCP) and sequencing were performed in 40 adenocarcinomas and 5 dysplasia of stomach. Thirteen cases, which had lymph node metastasis, were also included for immunohistochemical staining. Results: Inappropriate cytoplasmic and/or nuclear expression of a E-cadherin-$\beta-catenin$ complex was more frequent in poorly differentiated, diffuse type signet ring cell carcinomas than in well-differentiated, intestinal type adenocarcinomas (P<0.05). However, the expression was not related with clinical stage or lymph node metastasis. Mutation of E-cadherin was detected in 4 cases by using PCR-SSCP, whereas mutation of $\beta-catenin$ was detected in 2 cases. Conclusion: E-cadherin and $\beta-catenin$ seem to be important in gastric carcinogenesis, especially in poorly differentiated diffuse type.

• Journal of Digestive Cancer Research
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• 제11권3호
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• pp.165-170
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• 2023

Gastric cancer is histologically classified into two types. One is the intestinal and diffuse type according to Lauren's classification, and the other is the differentiated and undifferentiated type based on Nakamura's classification. In 2007, Japanese groups proposed a new type of well-differentiated gastric adenocarcinoma in the gastric fundic glands with distinct endoscopic and clinicopathologic features. This is gastric adenocarcinoma of the fundic-gland type (GA-FG), a rare variant of gastric cancer. In a 2012 Korean study, of 6,000 cases of gastric cancer tissues, only three cases of GA-FG were identified. GA-FG is usually located in the upper third of the stomach and not known to be associated with the Helicobacter pylori infection. We herein report a case of GA-FG diagnosed in a 63-year-old man. A gastric polyp was incidentally detected during an upper endoscopy screening while conducting a health check-up, and he was diagnosed with GA-FG after an endoscopic mucosal resection (EMR) was conducted for diagnostic and therapeutic purposes. Our case suggests that for both diagnostic and therapeutic purposes, EMR may be beneficial in case of gastric polyps with suspected GA-FG.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.190-194
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• 2007

Gastric adenocarcinoma (GA) is a major tumor type of gastric cancers and subdivides into several different tumors such as papillary, tubular mucinous, signet-ring cell and adenosquamous carcinoma according to histopatholigical determination. In other hand, GA is also subdivided into intestinal and diffuse type of adenocarcinoma by the Lauren?fs classification. In this study, we have examined differential gene expression pattern analysis of three histologically different GAs of 24 samples by using DNA microarray containing approximately 19000 genetic elements. The hierarchical clustering analysis of 24 gastric adenocarcinomas (12 of intestinal type, 7 of diffuse type and 5 of mixed type) resulted in two major subgroup on dendrogram, and two subgroups included most of intestinal and diffused type of GAs respectively. Supervised analysis of 19 intestinal and diffuse type GAs by using Wilcoxon rank T-test (P<0.01) resulted in 100 outlier genes which exactly separated intestinal and diffuse type of GA by differential gene expression. In conclusion, genome-wide analysis of gene expression of GAs suggested that GAs may subclassify as intestinal and diffused type of GA by their characteristic molecular expression. Our results also provide large-scale genetic elements which reflect molecular differences of intestinal and diffuse type of GAs, and this may facilitate to understand different molecular carcinogenesis of gastric cancer.

• Journal of Gastric Cancer
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• 제3권1호
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• pp.44-49
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• 2003

Purpose: The aim of this study was to investigate the impact of survivin expression and the decrease or loss of KAI-1 on the clinical stage and the survival rate in gastric adenocarcinomas. Materials and Methods: Expressions of survivin and KAI-1 were immunohistochemically determined in 40 cases of gastric adenocarcinomas. The survivin and KAI-1 expressions were also analyzed by using western blots in 14 cases among them. Results: Resected gastric cancer specimens from 40 patients (intestinal type: 15 cases and diffuse type: 25 cases) were evaluated immunohistochemically. Survivin protein expressions were significantly higher in diffuse types (P=0.03) and in advanced clinical stages (UICC TNM II and III, P=0.02). In contrast, a decrease or loss of KAI-1 expression had no statistically significant correlation with the Lauren classification or the clinical stage. Survivin protein positivity was associated with an unfavorable prognosis. Decrease or loss of KAI-1 was associated with a shorter disease free survivial rate (P < 0.01). The western blot data (n=14) indicated that neither survivin protein over-expression nor KAI-1 down-expression had an significant correlation with the Lauren classification or the clinical stage. Conclusion: In gastric carcinomas, survivin over-expression and decrease or loss of KAI-1 were associated with unfavorable prognosis, being independent prognostic factors along with the clinical stage and the disease free survival rate.

• Journal of Gastric Cancer
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• 제1권1호
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• pp.4-9
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• 2001

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

• Journal of Gastric Cancer
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• 제7권1호
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• pp.23-30
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• 2007

목적: 위암 환자 수술 후 재발의 임상병리학적 특성에 대한 이해는 재발의 조기 발견과 이에 따른 보다 나은 치료 성적을 얻기 위하여 필수적인 정보이다. 즉 종양의 특성에 따른 재발의 유형, 재발시기, 재발 이후의 경과 등을 이해하고자 본 연구를 시행하였다. 대상 및 방법: 1992년 6월부터 2005년 12월까지 본원 외과에서 위암으로 근치적수술을 시행 받은 1,338명의 환자 가운데 재발 유형을 모르는 경우(n=60), 사고사 및 타 질환으로 사망한 경우(n=55)를 제외한 1,223명을 연구 대상자로 하였다. 재발예(n=241)와 비재발예(n=982) 사이의 임상병리학적 특성 및 재발예 가운데 재발의 유형에 따른 임상병리학적 특성을 비교 분석하였다. 결과: 재발예는 비재발예에 비하여 위전절제술, 진행된 병기, 림프관이나 혈관 침윤예, 위전벽암, 크기가 큰 암, 미분화암, 미만형, Borrmann 4형이 의미 있게 많았다. 복막파종은 여성, stage III, 위상부 및 위전벽암, 미분화암, 미만형, Borrmann 4형이 의미 있게 많았고, 혈행성전이는 조기위암, stage I, 국소전이는 Borrmann 1, 2, 3형이 의미 있게 많았다. 복막파종의 경우 혈행성전이나 국소전이에 비하여 재발 후 생존기간이 짧았다(7.0개월, 9.5개월, 12.5개월). 조기재발군은 병기3, 4기, N3, 림프관침윤율이 높았고, 후기재발군은 병기3기, N1이 조기재발군에 비해 의미 있게 많았다. 결론: 위암의 임상병리학적 특성에 대한 이해가 위암수술 후 재발을 조기에 발견하는 데 중요할 것으로 판단된다.

• Journal of Gastric Cancer
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• 제10권3호
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• pp.106-110
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• 2010

Purpose: The purpose of this study was to analyze the clinical courses of patients with gastric cancer and positive resection margins after a gastrectomy for gastric cancer who did not undergo subsequent surgery. Materials and Methods: Among 4,452 patients who underwent surgery for gastric cancer from January 2001 to December 2007, 20 patients with positive resection margins after gastrectomy for gastric cancer who did not undergo subsequent surgery were included. The recurrence patterns were confirmed by postoperative computed tomography and gastroscopy, which were performed on a planned schedule. All recurrence patterns after gastrectomy were classified as loco-regional, peritoneal, or distant metastases. Results: The patients with confirmed recurrence all had advanced stage cancer (III-IV), and the recurrence sites were variable. However, peritoneal and distant recurrences were more common than loco-regional recurrences. The patients with loco-regional recurrence also had peritoneal and/or distant recurrence. Conclusions: Patients with gastric cancer and a positive resection margin showed more frequent peritoneal and distant metastases than loco-regional recurrence. In addition, patients with loco-regional recurrence also had peritoneal and distant recurrence. A positive resection margin of gastric cancer was related with poor histological differentiation, diffuse type, and advanced stage (III-IV).

• Journal of Gastric Cancer
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• 제14권4호
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• pp.238-245
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• 2014

Purpose: Gastric cancer often occurs in the elderly but is uncommon in young individuals. Whether young patients have different clinical behaviors and outcomes from those of older patients remain unclear. Materials and Methods: We identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010. We then compared the clinicopathological features and survival among the different age groups. Results: The male : female ratio differed significantly between the younger and older patient groups (0.84 in age <50 years vs. 1.52>60 years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs. 19% patients ${\geq}70$ years, P<0.0001), while more older patients were Caucasian (49% patients ${\geq}70$ years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed histological type was more prevalent in younger patients (70% patients <40 years vs. 27% patients ${\geq}70$ years; P<0.0001), whereas the intestinal type was more frequent in older patients (71% in patients ${\geq}70$ years vs. 30% in patients <40 years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the younger patients (80% in patients <40 years vs. 60% in patients ${\geq}70$ years; P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing age (overall P=0.0002). Conclusions: Young patients with gastric cancer had more aggressive disease but higher overall survival rates than older patients. Younger Hispanic patients and older Caucasian patients were more likely to be diagnosed with gastric cancer. These differences may be due to biological predisposition and/or environmental exposure.