• 동의생리병리학회지
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• 제23권5호
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• pp.1041-1048
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• 2009

The development of skin metastasis is usually a morbid prognostic feature although they occur infrequently. Adenocarcinomas account for up to about 70% of all metastatic skin cancer. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site because they don't have distinctive histological features. For this reason, immunohistochemistry have been used to help identify the origin of metastatic adenocarcinomas. This study performed immunohistochemical staining with metastatic adenocarcinomas of the skin using a variety of antisera to find out characteristic immunohistochemical findings of them. This study was made upon the 29 cases of metastatic adenocarcinomas of the skin, which had been confirmed histopathologically in Chonbuk National University Hospital from January, 1986 to April, 2006, Paraffin blocks were colledted and homemade tissue arrays were made. We performed immunohistochemical staning using 12 antibodies (MUC1, 2, 5AC, 6, cytokeratin (CK) 7, 20, thyroid transcription factor-1 (TTF-1), estrogen receptor (ER), progesterone receptor (PR), beta-catenin, cox-2, claudin-1). The mean age at the time of diagnosis was 60.7 years and the male to female ratio was 1.2:1.0. The most common primary site was lung, followed by stomach and colorectum. MUC1 was expressed by most colorectal, breast and lung adenocarcinoma. MUC2 was expressed infrequently. MUCSAC was expressed by most gastric and colorectal cancer MUC6 was not specific of any primary site in this series. CK7+/CK20+immunophenotype was observed in gastric, lung, colorectal adenocarcinoma. CK7+/CK20- immunophenotype was observed in breast, lung, endometrial, uterine cervical, bile duct adenocarcinoma, while CK7-/CK20+ immunophenotype was observed only in colorectal adenocarcinoma. This results show the utility of TTF-1 to confirm the pulmonary origin. On the other hand ER and PR were not useful markers to assess the origin of primary tumor in this series.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2777-2783
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• 2015

Background: Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. Materials and Methods: The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Results: Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Conclusions: Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6067-6071
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• 2015

Background: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. Materials and Methods: A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Results: Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. Conclusions: On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.

• Journal of Gastric Cancer
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• 제23권2호
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• pp.289-302
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• 2023

Purpose: Liver metastasis (LM) is reported in approximately 40% of patients with advanced/metastatic gastric/gastroesophageal junction adenocarcinoma (metastatic esophagogastric adenocarcinoma; mGEA) and is associated with a worse prognosis. This post-hoc analysis from the RAINBOW trial reported the efficacy, safety, and biomarker outcomes of ramucirumab and paclitaxel combination treatment (RAM+PAC) in patients with (LM+) and without (LM-) LM at baseline. Materials and Methods: Patients (n=665) were randomly assigned on a 1:1 basis to receive either RAM+PAC (LM+: 150, LM-: 180) or placebo and paclitaxel (PL+PAC) (LM+: 138, LM-: 197). The overall survival (OS) and progression-free survival (PFS) were evaluated using stratified Kaplan-Meier and Cox regression models. The correlation of dichotomized biomarkers (VEGF-C, D; VEGFR-1,2) with efficacy in the LM+ versus LM- subgroups was analyzed using the Cox regression model with reported interaction P-values. Results: The presence of LM was associated with earlier progression than those without LM, particularly in patients receiving PL+PAC (hazard ratio [HR], 1.68). RAM+PAC treatment improved OS and PFS irrespective of LM status but showed greater improvement in LM+ than that in LM- (OS HR, 0.71 [LM+] vs. 0.88 [LM-]; PFS HR, 0.47 [LM+] vs. 0.76 [LM-]). Treatment-emergent adverse events were similar between patients with and without LM. No predictive relationship was observed between biomarker levels (VEGF-C, D; VEGFR-1,2) and efficacy outcome (OS, PFS) (all interaction P-values >0.05). Conclusions: RAM provided a significant benefit, irrespective of LM status; however, its effect was numerically stronger in patients with LM. Therefore, RAM+PAC is a clinically meaningful therapeutic option for patients with mGEA and LM.

• Journal of Gastric Cancer
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• 제1권3호
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• pp.150-154
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• 2001

Purpose: Multiple early gastric cancers were found in $6.9\∼11.7\%$ of patients with early gastric cancer. The goal of this study was to clarify the clinicopathologic features of and to investigate treatment strategy for multiple early gastric cancer. Materials and Methods: Of 967 patients with an gastric adenocarcinoma who were treated by surgical resection during the period of $1993\∼1998$ at the Department of Surgery, Korea University College of Medicine, 267 patients had early gastric cancer. A retrospective analysis of the clinicopathologic differences between the main and the accessory lesions in multiple early gastric cancer was carried out. A comparative analysis was also conducted between solitary early gastric cancer and multiple early gastric cancer. Results: Of 267 patients with early gastric cancer, multiple early gastric cancers were found in 12 patients ($4.5\%$), including 10 men and 2 women. Eleven patients with multiple early gastric cancer had one accessory lesion and 1 patient had 2 accessory lesions. Of the 13 accessory lesions, 7 ($53.8\%$) were located in the same region as the main lesion. The most frequent combination of macroscopic types for the main lesion and the accessory lesion were depressed and depressed types (6 cases, $46.1\%$). The most frequent histologic type of main lesion was a well differentiated adenocarcinoma in 7 ($58.3\%$) of the 12 cases; the accessory lesion was also well differentiated in 4 of those 7 cases. Of the 13 accessory lesions, 4 ($30.8\%$) had been overlooked preoperatively; most of them were located in the lower third of the stomach and were IIb or IIc type and measured less than 1 cm in diameter. Lymph node metastasis was detected in 1 patient ($8.3\%$). The clinicopathologic features of multiple early gastric cancer were not different from those of solitary early gastric cancer. Conclusion: In multiple early gastric cancer, the main and the accessory lesions showed similar differentiation, and lymph node metastasis was less frequent than in solitary early gastric cancer. Therefore, limited procedures, including endoscopic mucosal resection, may be indicated if each lesion of the multiple early gastric cancer fits the criteria for treatment strategy.

• Journal of Gastric Cancer
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• 제12권2호
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• pp.55-62
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• 2012

There has been a large amount of speculation concerning the differences in the outcomes in patients who have gastric cancer in the Eastern and Western worlds. The differences in biology, surgical and adjuvant treatment have been used to explain such differences. There are clear differences observed in the histology (diffuse vs. intestinal), tumor location (proximal vs. distal), environmental exposures, dietary factors and Helicobacter pylori status. A higher incidence of gastric cancer in the East has led to screening programs, and leading to an earlier stage at presentation. Surgical treatment differs in that the extended lymph node dissection is routinely practiced in the Asian countries. Additionally, different adjuvant therapeutic regimens are used in both regions. The purpose of this review is to describe the differences in both presentation and treatment between the East and the West.

• Journal of Gastric Cancer
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• 제1권1호
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

• Journal of Gastric Cancer
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• 제4권3호
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• pp.164-168
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• 2004

Purpose: The most feared complication of gastrointestinal tract operations is anastomotic leakage, not only because of the presumed individual surgeon's culpability but also because of the assumption that this event is often fatal. We have experienced 32 cases of anastomotic leakage after elective gastric resection during 8 years. The purpose of this study was to evaluate the result of their treatment. Materials and Methods: We evaluated the records of 1335 patients who had undergone elective gastric resection for an adenocarcinoma of stomach from January 1995 to October 2003 and conducted a retrospective, multivariate analysis. Results: Of the 1335 patients, 32 ($2.4\%$) sustained an anastomotic leakage. Anastomotic leakages usually developed on mean postoperative day $9.1\pm3.2$ (range:$1\∼18$ days).Overall, $31.3\%$ (10/32) of patients who sustained an anastomotic leakage died. The anastomotic leakages were identifed by radiological study or by operative finding at the site of the duodenal stump (20 patients), the esophagojejunostomy (7), the gastroduodenostomy (4), and the gastrojejunostomy (1). Fourteen patients ($43.8\%$) underwent a relaparotomy, a drainage procedure in the main, and 18 patients ($56.3\%$) were treated conservatively. The mortality rates were $42.9\%$ (6/14) and $22.2\%$ (4/18), respectively, but this difference was not statistically significant. A cox's proportional hazard analysis showed that a body-mass Index < 24 kg/m2 (odds ratio 5.55, $95\%$ CI: $0.69\∼44.82$) and non-enteral feeding (odds ratio 18.27, $95\%$ CI 2.22.150.69) were independent factors of mortality due to anastomotic leakage. Conclusion: Our observations show that anastomotic leakage after an elective gastric resection has a high risk of being fatal. Moreover, for a patient with a body-mass index lower than $24\;kg/m^{2}$ and/or non-enteral feeding, an anastomotic leakage after an elective gastric resection has a higher risk of being fatal.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.164-172
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• 2014

Purpose: To evaluate the incidence, clinicopathological characteristics, treatment outcomes, prognostic factors, and survival of gastric cancer patients with bone metastases. Materials and Methods: Of 4,617 gastric cancer patients who were treated between 2001 and 2013, 176 patients with bone metastases were analyzed. Results: The incidence of bone metastasis was 3.8%. The most common histopathological subtype was adenocarcinoma (79%) with poor differentiation (60.8%). The median interval from the diagnosis to bone metastasis was 11 months. The median survival time after bone metastasis was 5.4 months. Factors that were associated with longer median survival times included the following: isolated bone metastasis (P=0.004), well-differentiated tumors (P=0.002), palliative chemotherapy (P=0.003), zoledronic acid treatment (P<0.001), no smoking history (P=0.007), and no metastatic gastric cancer at the time of diagnosis (P=0.01). On the other hand, high levels of lactate dehydrogenase (LDH) (hazard ratio [HR]: 1.86; P=0.015), carcinoembryonic antigen (CEA) (HR: 2.04; P=0.002), and carbohydrate antigen (CA) 19-9 (HR: 2.94; P<0.001) were associated with shorter survival times. In multivariate analysis, receiving zoledronic acid (P<0.001) and performance status (P=0.013) were independent prognostic factors. Conclusions: Smoking history, poor performance status, poorly differentiated adenocarcinoma, and high levels of LDH, CEA, and CA 19-9 were shown to be poor prognostic factors, while receiving chemotherapy and zoledronic acid were associated with prolonged survival in gastric cancer patients with bone metastases.

• Journal of Gastric Cancer
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• 제3권3호
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• pp.145-150
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• 2003

Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than $10\%$), twelve cases as postive (more than $10\%$). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P<0.05), However, there was no significant correlation between p53 mutation observed by DNA sequencing after laser capture microdissection and expression of p53 oncoprotein. Conclusion: These result suggest that he expression of p53 oncoprotein not to be related to the mutation of p53 gene at exons 4 through 9 in gastric cancer.