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1.  CHD1L Is a Marker for Poor Prognosis of Hepatocellular Carcinoma after Surgical Resection 
Korean Journal of Pathology  2013;47(1):9-15.
Background
The gene for chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) was recently identified as a target oncogene within the 1q21 amplicon, which occurs in 46% to 86% of primary hepatocellular carcinoma (HCC) cases. However, the prognostic significance of CHD1L in HCC remains uncertain. In this study, we investigated the roles of CHD1L in the prognosis of HCC.
Methods
We investigated the expressions of CHD1L in tumor tissue microarrays of 281 primary HCC patients who underwent surgical resection using immunohistochemistry. Prognostic factors of HCC were examined by univariate and multivariate analyses. The median follow-up period was 75.6 months.
Results
CHD1L expression was observed in 48 of the 281 HCCs (17.1%). CHD1L expression was associated with a younger age (p=0.033), higher Edmondson grade (p=0.019), microvascular invasion (p<0.001), major portal vein invasion (p=0.037), higher American Joint Committee on Cancer T stage (p=0.001), lower albumin level (p=0.047), and higher α-fetoprotein level (p=0.002). Multivariate analyses revealed that CHD1L expression (p=0.027), Edmondson grade III (p=0.034), and higher Barcelona Clinic Liver Cancer stage (p<0.001) were independent predictors of shorter disease-free survival.
Conclusions
CHD1L expression might be a prognostic marker of shorter disease-free survival in HCC patients after surgical resection.
doi:10.4132/KoreanJPathol.2013.47.1.9
PMCID: PMC3589617  PMID: 23482400
CHD1L; Carcinoma, hepatocellular; Survival
2.  Low SP1 Expression Differentially Affects Intestinal-Type Compared with Diffuse-Type Gastric Adenocarcinoma 
PLoS ONE  2013;8(2):e55522.
Specificity protein 1 (SP1) is an essential transcription factor that regulates multiple cancer-related genes. Because aberrant expression of SP1 is related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. Although patient survival decreased as SP1 expression increased (P<0.05) in diffuse-type gastric cancer, the lack of SP1 expression in intestinal-type gastric cancer was significantly correlated with poor survival (P<0.05). The knockdown of SP1 in a high SP1-expressing intestinal-type gastric cell line, MKN28, increased migration and invasion but decreased proliferation. Microarray data in SP1 siRNA-transfected MKN28 revealed that the genes inhibiting migration were downregulated, whereas the genes negatively facilitating proliferation were increased. However, both migration and invasion were decreased by forced SP1 expression in a low SP1-expressing intestinal-type gastric cell line, AGS. Unlike the intestinal-type, in a high SP1-expressing diffuse-type gastric cell line, SNU484, migration and invasion were decreased by SP1 siRNA. In contrast to previous studies that did not identify differences between the 2 histological types, our results reveal that low expression of SP1 is involved in cancer progression and metastasis and differentially affects intestinal-type compared with diffuse-type gastric adenocarcinoma.
doi:10.1371/journal.pone.0055522
PMCID: PMC3577840  PMID: 23437057
3.  Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma 
Diagnostic Pathology  2012;7:102.
Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001
doi:10.1186/1746-1596-7-102
PMCID: PMC3487888  PMID: 22894753
Neuroendocrine tumor; Adenoma; Microcarcinoid; Diagnosis
4.  Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases 
Korean Journal of Pathology  2012;46(3):287-291.
Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.
doi:10.4132/KoreanJPathol.2012.46.3.287
PMCID: PMC3479759  PMID: 23110017
Stomach neoplasms; Fundic gland; Chief cells, gastric; Cell differentiation; Pepsinogen A
5.  Glomus Tumor of the Stomach: A Clinicopathologic Analysis of 10 Cases and Review of the Literature 
Gut and Liver  2012;6(1):52-57.
Background/Aims
Gastric glomus tumors are extremely rare, and presurgical confirmation is often impossible. The identification of clinical and radiologic characteristics of this tumor type is important for preoperative diagnosis and treatment planning.
Methods
In this study, we analyzed 10 cases of gastric glomus tumors resected at a single institute over 9 years.
Results
Eight of the patients were men and 2 were women, with a mean age of 49 years. Five patients presented with abdominal discomfort or pain, 1 presented with anemia, and the remaining 4 cases were found incidentally during endoscopic examinations. The most common location of the tumor was the antrum (n=7), followed by the low (n=2) and high body (n=1). Although the endoscopic ultrasonography findings were variable, contrast-enhanced computed tomography generally showed a strong homogeneous enhancement. The resected tumors were well-demarcated solid masses with sizes ranging from 1.0 to 3.6 cm. Microscopically, the masses were composed of abundant vascular channels with clusters of uniform and round glomus cells. There was no evidence of recurrence after complete surgical resection.
Conclusions
Gastric glomus tumors are unusual, distinct lesions that should be considered in the differential diagnosis of a gastric submucosal mass. Unlike their deep soft tissue counterparts, most glomus tumors in the stomach are benign.
doi:10.5009/gnl.2012.6.1.52
PMCID: PMC3286739  PMID: 22375171
Glomus tumor; Stomach; Endoscopy; Pathology; Radiology
6.  Diagnosis of gastric epithelial neoplasia: Dilemma for Korean pathologists 
The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei, high nuclear/cytoplasmic ratio, loss of nuclear polarity, thick and irregular nuclear membrane, and nucleoli.
doi:10.3748/wjg.v17.i21.2602
PMCID: PMC3110921  PMID: 21677827
Intraepithelial neoplasia; Stomach; Dysplasia; Adenoma; Carcinoma; Japanese; Western; Consensus; Vienna
7.  Prediction of Complete Necrosis of Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Prior to Liver Transplantation 
Gut and Liver  2009;3(4):285-291.
Background/Aims
Compact lipiodol uptake without enhancement on multiphasic helical computed tomography (CT) has been suggested as a radiologic response criterion in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) and subsequent partial hepatectomy. However, its usefulness has not been fully investigated in the explanted liver.
Methods
Between 1998 and 2007, 81 patients with HCC underwent 1-9 sessions of TACE followed by liver transplantation (LT). Thirty-nine tumors in 29 patients showed a radiologic response on CT performed prior to LT. The radiologic response criteria and the duration of the response were evaluated to predict total necrosis in the explanted liver.
Results
Among the 39 tumors, 34 nodules (87.2%) exhibited total pathological necrosis. While 13 out of 16 tumors (81.3%) with a radiologic response for 6 months or less were completely necrotic, 21 out of 23 tumors (91.3%) with a radiologic response of longer than 6 months showed total necrosis.
Conclusions
Our results suggested that the radiologic response criteria based on serial CT images might be useful for predicting total necrosis of TACE-pretreated HCC in LT.
doi:10.5009/gnl.2009.3.4.285
PMCID: PMC2852730  PMID: 20431762
Explanted liver; Pathology; Computed tomography; Radiologic response
8.  The Clinicopathological Features of Gastric Hyperplastic Polyps with Neoplastic Transformations: A Suggestion of Indication for Endoscopic Polypectomy 
Gut and Liver  2009;3(4):271-275.
Background/Aims
Although gastric hyperplastic polyps are usually considered as benign lesions, a low risk of carcinomatous conversion is currently recognized. We aimed to identify the characteristics of hyperplastic polyps undergoing neoplastic transformation.
Methods
A total of 269 gastric hyperplastic polyps from 216 patients removed by endoscopic polypectomy (EP) or surgical resection were enrolled in this study, and their endoscopic pictures and pathology slides were reviewed.
Results
Neoplastic transformation was detected on forceps biopsy specimen in 11 cases. However, the pathology findings from the EP or surgical specimen revealed neoplastic transformation in 14 cases (5.2%; 4 with dysplasia and 10 with adenocarcinoma). No significant difference was found between hyperplastic polyps with and without neoplastic transformation in age, sex, location, number of polyps or gross appearance. However, neoplastic transformations were more frequently found in gastric hyperplastic polyps >1 cm than in polyps ≤1 cm (12 of 143; 8.4% vs. 2 of 126; 1.6%) (p=0.013).
Conclusions
Neoplastic transformations were more frequently found in gastric hyperplastic polyps >1 cm. Therefore, EP should be considered for gastric hyperplastic polyps >1 cm for the accurate diagnosis and definitive treatment.
doi:10.5009/gnl.2009.3.4.271
PMCID: PMC2852734  PMID: 20431760
Hyperplastic polyp; Neoplastic transformation; Endoscopic polypectomy
9.  Carney Triad in an Adult with Aggressive Behavior: The First Case in Korea 
Yonsei Medical Journal  2009;50(5):709-712.
Carney triad is a rare syndrome of unknown etiology characterized by having at least two out of three following neoplasms: gastrointestinal stromal tumor, pulmonary chondroma and extra-adrenal paraganglioma. About 100 cases have been reported worldwide. We report a case of Carney triad in a 42-year-old woman presented with a gastrointestinal stromal tumor in the stomach and a malignant functioning paraganglioma in the retroperitoneum that was fatal five years after diagnosis. The gastrointestinal stromal tumor was diagnosed as intermediate-risk of aggressive behavior and diffusely positive for c-kit whereas the retroperitoneal paraganglioma was negative for c-kit. Genetic analyses showed no mutations of KIT, PDGFRA, SDHB, SDHC, and SDHD genes in both tumors. To our best knowledge, this is the first case of Carney triad in Korea.
doi:10.3349/ymj.2009.50.5.709
PMCID: PMC2768248  PMID: 19881977
Carney triad; gastrointestinal stromal tumor; paraganglioma; malignant
10.  Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q 
To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop useful prognosis predictors, it is necessary to identify biologically relevant genomic alterations in HCC. In our study, we defined recurrently altered regions (RARs) common to many cases of HCCs, which may contain tumor-related genes, using whole-genome array-CGH and explored their associations with the clinicopathologic features. Gene set enrichment analysis was performed to investigate functional implication of RARs. On an average, 23.1% of the total probes were altered per case. Mean numbers of altered probes are significantly higher in high-grade, bigger and microvascular invasion (MVI) positive tumors. In total, 32 RARs (14 gains and 18 losses) were defined and 4 most frequent RARs are gains in 1q21.1-q32.1 (64.5%), 1q32.1-q44 (59.2%), 8q11.21-q24.3 (48.7%) and a loss in 17p13.3-p12 (51.3%). Through focusing on RARs, we identified genes and functional pathways likely to be involved in hepatocarcinogenesis. Among genes in the recurrently gained regions on 1q, expression of KIF14 and TPM3 was significantly increased, suggesting their oncogenic potential in HCC. Some RARs showed the significant associations with the clinical features. Especially, the recurrent loss in 9p24.2-p21.1 and gain in 8q11.21-q24.3 are associated with the high tumor grade and MVI, respectively. Functional analysis showed that cytokine receptor binding and defense response to virus pathways are significantly enriched in high grade-related RARs. Taken together, our results and the strategy of analysis will help to elucidate pathogenesis of HCC and to develop biomarkers for predicting behaviors of HCC.
doi:10.1002/ijc.23901
PMCID: PMC2698448  PMID: 18803288
hepatocellular carcinoma; recurrently altered regions; array comparative genomic hybridization; KIF14; TPM3
11.  SPIO-Enhanced MRI Findings of Well-Differentiated Hepatocellular Carcinomas: Correlation with MDCT Findings 
Korean Journal of Radiology  2009;10(2):112-120.
Objective
This study was designed to assess superparamagnetic iron oxide (SPIO)-enhanced MRI findings of well-differentiated hepatocellular carcinomas (HCCs) correlated with their multidetector-row CT (MDCT) findings.
Materials and Methods
Seventy-two patients with 84 pathologically proven well-differentiated HCCs underwent triple-phase MDCT and SPIO-enhanced MRI at a magnetic field strength of 1.5 Tesla (n = 49) and 3.0 Tesla (n = 23). Two radiologists in consensus retrospectively reviewed the CT and MR images for attenuation value and the signal intensity of each tumor. The proportion of hyperintense HCCs as depicted on SPIO-enhanced T2- or T2*-weighted images were compared in terms of tumor size (< 1 cm and > 1 cm), five CT attenuation patterns based on arterial and equilibrium phases and magnetic field strength, by the use of univariate and multivariate analyses.
Results
Seventy-eight (93%) and 71 (85%) HCCs were identified by CT and on SPIO-enhanced T2- and T2*-weighted images, respectively. For the CT attenuation pattern, one (14%) of seven isodense-isodense, four (67%) of six hypodense-hypodense, four (80%) of five isodense-hypodense, 14 (88%) of 16 hyperdense-isodense and 48 (96%) of 50 hyperdense-hypodense HCCs were hyperintense (Cochran-Armitage test for trend, p < 0.001). Based on the use of multivariate analysis, the CT attenuation pattern was the only factor that affected the proportion of hyperintense HCCs as depicted on SPIO-enhanced T2- or T2*-weighted images (p < 0.001). Tumor size or magnetic field strength was not a factor that affected the proportion of hyperintense HCCs based on the use of univariate and multivariate analysis (p > 0.05).
Conclusion
Most well-differentiated HCCs show hyperintensity on SPIO-enhanced MRI, although the lesions show various CT attenuation patterns. The CT attenuation pattern is the main factor that affects the proportion of hyperintense well-differentiated HCCs as depicted on SPIO-enhanced MRI.
doi:10.3348/kjr.2009.10.2.112
PMCID: PMC2651447  PMID: 19270856
Well-differentiated hepatocellular carcinoma; Superparamagnetic iron oxide-enhanced MRI, MDCT
12.  Early Hepatocellular Carcinoma: Three-Phase Helical CT Features of 16 Patients 
Korean Journal of Radiology  2008;9(4):325-332.
Objective
To evaluate the three-phase helical CT features of early hepatocellular carcinomas, based on the new Japanese classification.
Materials and Methods
Over the course of an eight-year period, we collected 16 pathologically proven early hepatocellular carcinomas from 16 patients having undergone a three-phase helical CT prior to surgery. The three-phase CT images were acquired at 20-35 sec (arterial phase), 70 sec (portal phase), and 180 sec (equilibrium phase) from the begining of intravenous injection of contrast material. All the CT images were retrospectively analyzed by two radiologists in consensus, based on their description of morphologic (size, margin, fibrous capsule and mosaic pattern) and enhancement patterns of tumors.
Results
Only seven (44%) of the 16 early hepatocellular carcinomas having undergone a CT were described (mean diameter, 1.2 cm; range, 0.4-2.5 cm). All the tumors had an ill-defined margin with no fibrous capsule. The mosaic pattern was found in only one tumor. Only three (43%) of the seven tumors detected on CT were hyperattenuating during the arterial phase. The four remaining tumors (25%) were hypoattenuating throughout the three phases.
Conclusion
Despite the higher resolution provided by the three phase scans, the contrast-enhanced CT provides only limited detection of the variable morphologic and enhancement features of early hepatocellular carcinomas.
doi:10.3348/kjr.2008.9.4.325
PMCID: PMC2627272  PMID: 18682670
Hepatocellular carcinoma; Liver neoplasms; Computed tomography (CT)
13.  Endoscopic Screening for Remnant Gastric Cancer: Points to be Considered 
Gut and Liver  2007;1(1):22-26.
Background/Aims
It is difficult to detect early gastric cancer (EGC) during endoscopic surveillance because the remnant stomach is usually deformed after surgical resection and the mucosa at the gastric stump are changed due to bile reflux. In this study, we aimed to determine the characteristic endoscopic findings of cancer in the remnant stomach.
Methods
Fifty-five remnant gastric cancer (RGC) patients were classified into three groups according to location and elapsed time after surgery. Among 32 RGCs that developed less than 10 years after surgery, 21 lesions were located close to the anastomosis site (recurrent cancers), whereas 11 lesions were not (residual cancers). Twenty-three cancers developed at least 10 years after surgery (newly developed cancers). The endoscopic features were compared among these groups.
Results
Most patients (29/32, 91%) with residual or recurrent cancer developed their tumors within five years after surgery, and the proportion of EGC was 43.8% (14/32). However, 91.3% (21/23) of newly developed cancers were advanced gastric cancers. When classified according to the Japanese classification system for EGC, 71% (5/7) of the residual cancers were of the elevated type, whereas 86% (6/7) of the recurrent cancers were of the depressed type (p=0.00).
Conclusions
During the first 5 years after subtotal gastrectomy, endoscopists should mainly try to find depressed lesions on the anastomosis site as well as elevated lesions on the non-anastomosis site.
doi:10.5009/gnl.2007.1.1.22
PMCID: PMC2871652  PMID: 20485654
Gastric cancer; Stump; Gastrectomy
14.  Gastric Syphilis Mimicking Adenocarcinoma: A Case Report 
Journal of Korean Medical Science  2006;21(3):559-562.
Syphilis is an unexpected diagnosis in the stomach, and the reduced incidence of syphilis has made its clinical presentation less widely appreciated. We report a 43-yr-old man suffering from epigastric tenderness with an initial diagnosis of gastric carcinoma; gastric syphilis was confirmed by demonstrating spirochetes in a gastric biopsy specimen by silver impregnation. Excessive lymphoplasmacytic infiltration with diffuse thickening of gastric rugae should raise suspicion of gastric syphilis, which should be considered in the differential diagnosis of diffuse erosive gastritis and infiltrative lesions of the stomach.
doi:10.3346/jkms.2006.21.3.559
PMCID: PMC2729968  PMID: 16778406
Stomach; Syphilis; Gastritis; Treponema Pallium
15.  Isolated Biliary Granulocytic Sarcoma Followed by Acute Myelogeneous Leukemia with Multilineage Dysplasia: A Case Report and Literature Review 
Journal of Korean Medical Science  2006;21(3):550-554.
Granulocytic sarcoma is a rare extramedullary tumor composed of myeloid progenitor cells. Primary involvement of the biliary tract without evidence of leukemia is exceedingly rare. Here, we report an isolated biliary granulocytic sarcoma in a 30-yr-old man who presented with jaundice, fever, and chill without any evidence of leukemia. However, five months after the diagnosis, he developed acute myelogenous leukemia with multilineage dysplasia and chromosomal abnormality. A rare possibility of biliary granulocytic sarcoma should be considered as a differential diagnosis in patients with obstructive jaundice. A histologic evaluation by aggressive diagnostic intervention is important and may improve prognosis.
doi:10.3346/jkms.2006.21.3.550
PMCID: PMC2729966  PMID: 16778404
Sarcoma, Granulocytic; Leukemia; Jaundice, Obstructive; Bile Ducts
16.  Mesenchymal Hamartomas of the Liver: Comparison of Clinicopathologic Features between Cystic and Solid Forms 
Mesenchymal hamartoma (MH) of the liver is an uncommon benign lesion related to ductal plate malformation. It is usually cystic and mainly composed of myxoid mesenchymal tissue with tortuous or cystic bile ducts. In order to characterize the clinicopathological features of MH, the Korean Gastrointestinal Pathology Study Group collected a total of 17 MH cases diagnosed in 7 hospitals from 1992 to 2002 and compared the clinicopathologic findings of cystic MH with those of solid variant. Among the 17 cases, 7 (41%) were solid. The solid form showed a higher serum level of α-fetoprotein (AFP), the smaller bile ducts, and more frequent proliferation of vessels. Serum AFP level was related to the amount of hepatocytes. Two of seven solid cases harbored a larger amount of evenly distributed hepatocytes and proliferation of small duct with focal hepatocyte-bile duct transition. These histologic findings are similar to those of mixed hamartoma. Therefore, the mixed hamartoma and the MH of both solid and cystic types could be the variants of one disease spectrum. And hepatocytes within MH might be rather a genuine tumor component than entrapped into the tumor. In conclusion, MH can show various clinicopathological features and recognition of these features will facilitate accurate diagnosis of MH.
doi:10.3346/jkms.2006.21.1.63
PMCID: PMC2733981  PMID: 16479067
Liver; Hamartoma; Hamartoma, Mesenchymal; Hepatocyte; alpha-Fetoproteins
17.  Gastrointestinal Stromal Tumors in Koreans: It's Incidence and the Clinical, Pathologic and Immunohistochemical Findings 
Journal of Korean Medical Science  2005;20(6):977-984.
Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p=0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p=0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.
doi:10.3346/jkms.2005.20.6.977
PMCID: PMC2779330  PMID: 16361808
Gastrointestinal Stromal Tumors; Immunohistochemistry; Incidence; Esophagus; Stomach; Intestine, small; Colon; Rectum; Korean
18.  Promoter Methylation of E-cadherin in Hepatocellular Carcinomas and Dysplastic Nodules 
Journal of Korean Medical Science  2005;20(2):242-247.
In order to clarify the significance of E-cadherin methylation in multistep hepatocarcinogenesis, we examined the methylation status of the E-cadherin promoter region, using methylation-specific polymerase chain reaction in 64 hepatocellular carcinomas (HCCs) and 13 dysplastic nodules (DNs), and correlated these results with E-cadherin protein expression and clinicopathologic factors of HCCs. Promoter methylation was detected in 1 of 13 (7.7%) DNs, in 5 of 13 (38.5%) Edmondson and Steiner grade I HCCs, and in 27 of 51 (52.9%) grade II or III HCCs, and a significant correlation was observed between the methylation status and the stepwise progression of hepatocarcinogenesis (p=0.004). Reduced E-cadherin immunoreactivity was found in 18 of 64 (28%) HCCs, but in none of DNs. E-cadherin methylation status in HCCs was significantly correlated with microvascular invasion (p=0.02) and tumor recurrence (p=0.04), but not with reduced E-cadherin immunoreactivity. The Kaplan-Meier method showed that methylation status did not have a significant influence on the recurrence-free survival of HCC patients (p=0.15). Our results indicate that methylation of the E-cadherin promoter region is a frequent event in HCC, which may play an important role in the stepwise progression of hepatocarcinogenesis. And the promoter methylation of E-cadherin in HCC was found to be significantly correlated with microvascular invasion and recurrence.
doi:10.3346/jkms.2005.20.2.242
PMCID: PMC2808600  PMID: 15831995
Carcinoma, Hepatocellular; Dysplastic Nodule; Cadherins; DNA Methylation
19.  Correlation of mutation and immunohistochemistry of p53 in hepatocellular carcinomas in Korean people. 
Journal of Korean Medical Science  2002;17(6):801-805.
The degree of correlation between sequencing and immunohistochemisty (IHC) for detecting mutations of p53 has not been well established in human hepatocellular carcinoma (HCC). We analyzed 36 HCCs from Korean people for p53 mutation at exons 4-10 by PCR-SSCP and sequencing, and compared the results with the IHC positivity. p53 mutations were identified in 7 out of 36 HCCs (19.4%). These mutations were found widely throughout exons 4-8. No mutation was detected in codon 249. Among the 7 mutations, 6 missense mutations were detected in 15 HCCs with > or =5% immunoreactive tumor cells and one nonsense mutation was in 21 HCCs with <5% immunoreactive tumor cells. The sensitivity for p53 mutation was 85.7% (6/7), the specificity 69.0% (20/29), the predictive value of positive IHC 40.0% (6/15), and the predictive value of negative IHC 95.2% (20/21). Two missense mutations were detected in 25 cases with <10% immunoreactive tumor cells. Predictive values of both positive IHC and negative IHC were higher in > or =5% overexpression group than in > or =10% overexpression group or >0% overexpression group. This study suggests that 5% immunoreactivity is a reliable immunohistochemical threshold value to detect p53 mutations in HCCs and the spectrum of p53 mutations in HCCs in Korean people is different from that of high aflatoxin B1 exposure areas.
PMCID: PMC3054961  PMID: 12483005
20.  Early Recurring Hepatocellular Carcinoma after Partial Hepatic Resection: Preoperative CT Findings 
Korean Journal of Radiology  2000;1(1):38-42.
Objective
The purpose of this study was to determine the utility of preoperative CT in predicting early recurrence of hepatocellular carcinoma after partial hepatic resection.
Materials and Methods
Preoperative three-phase helical CT scans in 53 patients with hepatocellular carcinoma were retrospectively reviewed by two radiologists. In 27 patients (group I), HCC had recurred within six months, while 26 (group II) had remained disease free for at least two years. In each group, preoperative CT findings were evaluated in each group for the tumor size and number, the presence or absence of capsule, distinctness of tumor margin, perinodular extension, and the presence or absence of portal vein thrombosis.
Results
In group I, a tumor capsule of tumor was seen in five of 27 patients (19%), and in group II, in 16 of 26 (62%) (p = .001). The tumor margin was distinct in eight patients (30%) in group I and in 20 (77%) in group II (p = .001). Multiple tumors, perinodular extension, and portal vein thrombosis were more frequently seen in group I but the differences were not statistically significant (p > .05). Tumor size was similar in each group (p > .05).
Conclusion
Preoperative CT findings that may help predict the early recurrence of hepatocellular carcinoma after surgical resection are an absence of capsule of tumors and an indistinct margin. Reference to these findings during preoperative CT can guide clinicians in their choice of treatment.
doi:10.3348/kjr.2000.1.1.38
PMCID: PMC2718136  PMID: 11752927
Liver, CT; Liver neoplasms, CT
21.  The effect of alkaline phosphatase and intrahepatic metastases in large hepatocellular carcinoma 
Background
Hepatectomy is the standard treatment for HCC. However, large HCC poses a difficult challenge because of the technical complexity of surgical resection and the fear of postoperative hepatic decompensation. We analyzed the outcome and prognostic factors in patients with large hepatocellular carcinoma (HCC ≥10 cm) after surgery.
Methods
We retrospectively investigated the medical records of 91 patients who had undergone hepatectomy between January 2006 and June 2010. A survival analysis was performed utilizing the Kaplan-Meier method and prognostic factors were evaluated using Cox regression analysis.
Results
Of the 91 patients evaluated, most tumors were associated with hepatitis B virus (HBV). The median tumor size was 12.3 cm (range, 10 to 21 cm), with microvascular invasion present in most patients. The postoperative mortality rate was 2.2%. The median disease-free survival and overall survival were six months and 41 months. The one-year, two-year, and three-year disease-free survival rates were 33.5%, 29.3%, and 18.8%, respectively. The one-year, two-year, and three-year overall survival rates were 73.9%, 63.7%, and 54.8%, respectively. Of the 89 surviving patients, 69 patients (77.5%) developed HCC recurrence during the mean follow-up period of 23.4 ± 15.9 months. On multivariate analysis, the statistically significant factors that predicted HCC recurrence were ALP ≥ 80 IU/mL (P = 0.009) and intrahepatic metastases (P = 0.013).
Conclusions
Our study suggests that preoperative ALP levels (≥ 80 IU/L) and intrahepatic metastases could be utilized to monitor and predict recurrence in HCC patients.
doi:10.1186/1477-7819-11-40
PMCID: PMC3598399  PMID: 23432910
Hepatocellular carcinoma; Liver resection; Metastasis; Survival
22.  The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy 
BMC Cancer  2011;11:344.
Background
Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear.
Methods
A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status.
Results
CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022).
Conclusions
Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results.
doi:10.1186/1471-2407-11-344
PMCID: PMC3162585  PMID: 21827707
23.  Metastatic lymph node in gastric cancer; Is it a real distant metastasis? 
BMC Cancer  2010;10:25.
Background
Currently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.
Methods
Among data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.
Results
In 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.
Conclusion
In this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.
doi:10.1186/1471-2407-10-25
PMCID: PMC2848187  PMID: 20113485
24.  Depiction of Viable Tumor in Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: Multiphasic Helical CT with Review of the Previous Serial CT Images 
Korean Journal of Radiology  2005;6(3):153-160.
Objective
The purpose of our study was to assess whether a review of multiphasic helical CT combined with the previous serial CT images could be helpful to depict a viable tumor in hepatocellular carcinoma treated with transarterial chemoembolization.
Materials and Methods
Twenty-four consecutive patients with 35 hepatocellular carcinomas underwent transarterial chemoembolization followed by hepatic resection. First, three radiologists independently analyzed the last CT images taken before resection for the presence of viable tumor. A second analysis was then performed using the last CT combined with the previous serial CT images. The CT analyses were then compared with the pathologic results. The added value of the review of the previous serial CT images was evaluated by performing a receiver operating characteristic analysis. The sensitivity, specificity and diagnostic accuracy for the depiction of viable tumor were also assessed, and the characteristics of the false-negative lesions were pathologically evaluated.
Results
The mean diagnostic accuracies (Az values) for the depiction of viable tumor with using the last CT alone and with the review of the previous serial CT images for all observers were 0.885 and 0.901, respectively, which were not significantly difference (p > 0.05). However, the additional review of the previous serial CT images allowed the observers to render a correct diagnosis for three lesions that had been incorrectly diagnosed with the review of last CT alone. The sensitivity, specificity and diagnostic accuracy of the last CT along with the review of the previous serial CT images were 78%, 97% and 84%, respectively. All of the 16 false-negative lesions diagnosed by each observer showed 90% or greater necrosis on the pathologic examination.
Conclusion
For the depiction of viable tumor in hepatocellular carcinoma treated with transarterial chemoembolization, although the difference in the diagnostic accuracies was not statistically significant, a review of the multiphasic helical CT combined with the previous serial CT images could help reach a correct diagnosis for those lesions incorrectly diagnosed with the review of the last CT alone.
doi:10.3348/kjr.2005.6.3.153
PMCID: PMC2685038  PMID: 16145290
Liver, CT; Liver neoplasm, CT

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