Min A Kim

Seoul National University Hospital, Sŏul, Seoul, South Korea

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Publications (102)330.13 Total impact

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    ABSTRACT: Purpose The purpose of this study is to compare the MRI features of intestinal and endocervical mucinous borderline ovarian tumors (MBOT). Methods Fifty seven and 17 patients with histologically proven intestinal (n = 62) and endocervical (n = 22) MBOT, respectively, underwent preoperative MRI which were reviewed by two radiologists blinded to histology. An array of MRI features and clinical factors (age, cancer antigen 125 [CA-125]) were compared between intestinal and endocervical subtypes using the t test and Chi-square test. Univariate and multivariate logistic regression analyses were performed to evaluate for significant predictors of subtype. Results There was no significant difference in patient age of intestinal and endocervical MBOT (P = 0.423). CA-125 levels were higher in endocervical MBOT (P = 0.022). Regarding MR features, intestinal MBOT was larger, had more septations, more frequently demonstrated honeycomb loculi, and signal intensity discrepancy while endocervical MBOT was more frequently bilateral with papillary projections (P P = 0.034) and the presence of papillary projections (OR 11.441, P = 0.024) were the only independent predictive factors of endocervical MBOT. Conclusion Intestinal and endocervical subtypes of MBOT demonstrated significantly different features on MRI. The presence of papillary projection was the only independent MRI feature predictive of endocervical MBOT.
    Abdominal Imaging 12/2014; · 1.91 Impact Factor
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    ABSTRACT: Success factors of laparoscopic nerve-sparing radical hysterectomy (LNRH) to preserve bladder function are little known despite its widespread use. Thus, we conducted a protocol-based prospective cohort study to evaluate clinicopathologic factors for preserving autonomic nerves and its impact on duration of postoperative catheterization (DPC). From 2012 to 2014, 30 patients with stage IB1 to IIA2 cervical cancer were recruited prospectively to undergo LNRH. All procedures were performed on the left side of the patients by one gynecologic oncologist. Extent of resection and preservation of autonomic nerves were documented in the protocol during LNRH. All patients received laparoscopic type C1 radical hysterectomy, where extent of resection and preservation of autonomic nerves were not different between the right and left sides. Stage IB1 disease was associated with the reduced risk of injury of the left junctions between the hypogastric and the splanchnic nerves; between the splanchnic nerve and the vesical branch of the pelvic plexus (S-V junction) (adjusted odds ratios, 0.06 and 0.06; 95 % confidence intervals, 0.01-0.92 and 0.01-0.48); the right S-V junction with marginal significance (adjusted odds ratio, 0.18; 95 % confidence interval, 0.03-1.06). Furthermore, bilateral preservation of autonomic nerves decreased DPC significantly when compared with failure or unilateral preservation (median, 6 days vs. 34 days or 57 days; P < 0.05). LNRH has a higher likelihood of its success in stage IB1 than in stage IB2 to IIA disease. Moreover, preservation of bilateral autonomic nerves reduces DPC significantly in comparison with failure or unilateral preservation.
    Annals of Surgical Oncology 12/2014; · 4.12 Impact Factor
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    ABSTRACT: Diabetic patients with endometrial cancer had more lymph node metastasis than non-diabetic patients with endometrial cancer. L1 cell adhesion molecule (L1CAM) could be possibly associated with lymph node metastasis in diabetic patients with endometrial cancer via epithelial-mesenchymal transition. We aimed to investigate the association between L1CAM expression and lymph node metastasis in diabetic patients with endometrial cancer.
    Journal of cancer prevention. 09/2014; 19(3):231-9.
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    ABSTRACT: The aim of this study is to identify a patient group with a low-risk of parametrial involvement (PMI) in Stage IB1 cervical cancer using preoperative magnetic resonance imaging (MRI) parameters. In total, 190 Stage IB1 cervical cancer patients with clinically visible lesions who had undergone Type C2 radical hysterectomy and preoperative MRI were included in this study. Clinical records, pathology reports, and preoperative MRI findings were reviewed retrospectively. Of the 190 patients, 19 (10%) had pathologic PMI. The largest tumor diameter identified by MRI ranged from zero (no definite mass on the cervix) to 60mm, with a median of 21mm. Patients were identified as being either low-risk (tumor size≤25mm and no evidence of PMI, n=127) or high-risk (tumor size>25mm and/or findings indicating PMI, n=63) based on MRI parameters. The rate of pathologic PMI in low- and high-risk patients was 0.0% and 30.2%, respectively (P<0.001). Five-year progression-free survival in low-risk patients was 95.9%, which is significantly better than the rate of 85.6% for patients in the high-risk group (P=0.039). Preoperative MRI parameters can help identify patients with a low-risk of PMI and, therefore, possible candidates for trials on less radical surgery.
    Gynecologic Oncology 04/2014; · 3.93 Impact Factor
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    ABSTRACT: Melanoma that involves the upper gastrointestinal (GI) tract is rare and studies relating to endoscopic and pathologic findings with clinical outcomes are lacking. We reviewed the gross and microscopic patterns of the upper GI tract in primary and metastatic melanoma, and examined their association with clinical outcomes. Twenty-nine cases of primary esophageal (n = 19) and metastatic gastric and/or duodenal melanoma (n = 10) that were detected during upper GI endoscopy between 1995 and 2011 were retrospectively analyzed. Three types of gross patterns were recognized-nodular pattern in 7 cases, mass-forming pattern in 18 cases, and flat pigmented pattern in 4 cases. In primary esophageal melanoma, 13 patients (68.4 %) underwent surgery and 9 received palliative therapy. Of all cases, 22 patients (75.9 %) died of disease progression; the median overall survival period was 12 months (interquartile range [IQR] 4.5-24.5 months), and from recognition of upper GI tract melanoma the median overall survival period was 9 months (IQR 3.5-17.0 months). In primary esophageal cases, skin melanoma stage better discriminated the patients with good prognosis than the esophageal cancer stage. The flat pigmented gross pattern proved to be a good prognostic factor in primary and metastatic GI tract melanomas (p = 0.016 and p = 0.046, respectively). Melanoma of the GI tract is a highly aggressive disease with a poor prognosis, both in primary and metastatic cases. However, in primary esophageal melanoma, careful inspection of the mucosa during endoscopic examination followed by surgical resection may result in extended survival.
    Annals of Surgical Oncology 03/2014; · 4.12 Impact Factor
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    ABSTRACT: Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock. Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats. All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1β, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05). Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.
    The journal of trauma and acute care surgery. 03/2014; 76(3):771-778.
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    ABSTRACT: FOXO1, a forkhead box O (FOXO) transcription factor, and nuclear factor-κB (NF-κB) are prognostically significant transcription factors in gastric cancer. As their relationship has been inconsistent depending on the cell type, we aimed to investigate whether FOXO1 is associated with NF-κB p65 (RelA) in gastric cancer. Immunohistochemistry was performed on tissue array slides containing 298 gastric carcinoma specimens. We found that the cytoplasmic expression of pFOXO1, the inactive form of FOXO1, was positively correlated with nuclear RelA expression (p = 0.024). In addition, the expressions of pFOXO1 and RelA were positively related with cyclin D1 expression (p = 0.014 and p = 0.001, respectively) and Ki-67 labeling index (p = 0.025 and p = 0.017, respectively). However, they did not show association with the expressions of cyclin E, p53 and pRb. Cell culture experiments showed that FOXO1 overexpression by transfection of FOXO1 AAA mutant gene suppressed NF-κB activation in SNU-484 gastric cancer cells. These results suggest that FOXO1 and NF-κB are negatively associated and that FOXO1 is a negative upstream regulator of NF-κB in gastric cancer.
    Apmis 03/2014; · 2.07 Impact Factor
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    ABSTRACT: Gastric adenocarcinoma is the sixth most common and third most lethal cancer in the world. Except for HER2-targeted therapy, targeted agents against specific molecules participating in gastric carcinogenesis, including those in the mechanistic target of rapamycin (serine/threonine kinase) (mTOR) pathway have not been proved to be effective. However, some studies have suggested that dysfunction of TSC1 may augment mTOR inhibitor activity. We studied p-mTOR and TSC1 status by immunohistochemical analysis of gastric carcinoma samples using a tissue microarray method and expression values adopted from The Cancer Genome Atlas. High p-mTOR and low TSC1 expression status is associated with adverse clinicopathologic parameters. Patients with high p-mTOR levels showed poor survival. Patients with low TSC1 levels showed unfavorable survival status in the overall patients group. The combination of p-mTOR status and TSC1 status provided more strong survival information than using each parameter alone. In gastric cancer, high p-mTOR expression level is a statistically significant parameter in multivariate and Kaplan-Meier analyses (log-rank test). In addition to p-mTOR, TSC1 expression provided additional information to predict survival. We therefore suggest that evaluation of both p-mTOR and TSC1 status may be helpful in clinical trials related to mTOR inhibitors. J. Surg. Oncol. © 2014 Wiley Periodicals, Inc.
    Journal of Surgical Oncology 02/2014; · 2.64 Impact Factor
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    ABSTRACT: The aim of this study was to compare the survival outcomes of adenosquamous carcinoma (ASC) and adenocarcinoma (AC) of the cervix. We searched PubMed and Embase for observational studies that compared the outcomes of 2 histologic subtypes. Hazards ratios (HRs) with 95% confidence intervals (CIs) were calculated with a fixed effects model. A total of 17 studies were included in the analyses. Patients with ASC were associated significantly with poorer overall survival (death HR, 1.27; 95% CI, 1.12-1.43; I = 0%) and recurrence-free survival (recurrence HR, 1.43; 95% CI, 1.05-1.95; I = 19.4%) than those with AC. For clinical stages I and II in particular, ASC predicted significantly poorer outcomes compared with AC (death HR, 1.41; 95% CI, 1.17-1.70; I = 0%). This meta-analysis suggests that ASC may have poorer outcomes compared with AC of the cervix.
    International Journal of Gynecological Cancer 01/2014; · 1.94 Impact Factor
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    ABSTRACT: We investigated MET mRNA expression status using RNA in situ hybridization (ISH) technique in primary and metastatic lesions of 535 surgically resected gastric carcinoma (GC) cases. We compared the results with those of immunohistochemistry and silver in situ hybridization, and examined the association with clinicopathologic characteristics and prognosis. Among 535 primary GCs, 391 (73.1%) were scored 0, 87 (16.3%) were scored 1, 38 (7.1%) were scored 2, 12 (2.2%) were scored 3 and 7 (1.3%) were scored 4 by RNA ISH. High MET mRNA expression (score ≥3) was associated with lymph node metastasis (P = .014), distant metastasis (P = .001), and higher TNM stage (P<.001). MET mRNA expression was correlated with protein expression (r = 0.398; P<.001) and gene copy number (r = 0.345; P<.001). The patients showing high-MET mRNA in primary or metastatic lesions had shorter overall survival than those showing low-MET mRNA (primary tumors, P = .002; metastatic lymph nodes, P<.001). The patients showing positive conversion of MET mRNA status in metastatic lymph node had shorter overall survival than those with no conversion (P = .011). Multivariate analysis demonstrated that high MET mRNA expression in metastatic lymph node was an independent prognostic factor for overall survival (P = .007). Therefore, this study suggests that MET mRNA expression assessed by RNA ISH could be useful as a potential marker to identify MET oncogene-addicted GC.
    PLoS ONE 01/2014; 9(11):e111658. · 3.53 Impact Factor
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) has been suggested to contribute to tumor progression and acquisition of therapeutic resistance. To assess the clinical significance of EMT-associated proteins, we evaluated the expression of Snail and Slug, the key regulators of EMT, in the primary ovarian cancer samples (n = 103) by immunohistochemistry. Snail was differentially expressed according to the histologic subtype (P = 0.001) and was predominantly expressed in serous and endometrioid types. In the serous and endometrioid adenocarcinomas, the expression of Snail remained high across the stage and grade, suggesting its role in the early phase of carcinogenesis. However, the expression of Snail and Slug was not related to chemoresistance and poor prognosis and did not serve as independent predictive or prognostic marker.
    BioMed research international. 01/2014; 2014:495754.
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    ABSTRACT: We investigated the roles of Lethal giant larvae 2 (Lgl2), an epithelial cell polarity protein, during gastric carcinogenesis and gastric cancer (GC) progression and evaluated the correlation of Lgl2 with epithelial-mesenchymal transition (EMT) markers. Lgl2 protein and mRNA expression were determined by immunohistochemistry and mRNA in situ hybridization in a large series of GC and preneoplastic lesions. Additionally, expression of 7 EMT markers was examined by immunohistochemistry. Loss of membrane Lgl2 staining in GC was observed in 347 of 409 GCs. Lgl2 loss was associated with diffuse histological type (P < 0.001), advanced stage (P = 0.021), and worse prognosis (P = 0.047). Furthermore, Lgl2 loss correlated with reduced E-cadherin expression (P < 0.01) and increased expression of vimentin (P < 0.01). Combined analysis of Lgl2 and the EMT markers, S100A4 and MMP2, improved predictions of patient outcomes. During gastric carcinogenesis, membrane expression of Lgl2 was progressively lost in 4 % of normal mucosa, 75 % of intestinal metaplasia, 58 % of gastric dysplasia, 69 % of intestinal type GC, and 96 % of diffuse type GC. Our results suggest that Lgl2 loss occurs at an early stage of gastric carcinogenesis and contributes to GC progression.
    Gastric Cancer 12/2013; · 3.99 Impact Factor
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    ABSTRACT: Cisplatin (CDDP) is one of the most important chemotherapeutic agents in the treatment of advanced gastric cancer, but its efficacy is limited by CDDP resistance. Because the transcription factor FOXO1 is related to chemoresistance in various cancer cells, we investigated the function of FOXO1 in CDDP resistance in human gastric cancer cells. Human gastric cancer cell lines MKN45 and SNU-601 were used. FOXO1 activation was modulated by transfection of FOXO1 AAA mutant gene or FOXO1 shRNA. The effects of FOXO1 on cell growth and CDDP cytotoxicity were assessed by crystal violet assay. Protein expressions of FOXO1, p110α, pAkt, and Akt were analyzed by Western blotting, and FOXO1 mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction. FOXO1 activity was determined by luciferase reporter assay, and cell apoptosis was assessed by DAPI staining and Western blotting for PARP cleavage. Cisplatin treatment induced FOXO1 expression and activation in both gastric cancer cell lines. FOXO1 overexpression increased the CDDP resistance without changes in cell growth, whereas FOXO1 silencing enhanced CDDP cytotoxicity along with apoptotic characteristics. Both constitutive and CDDP-induced FOXO1 activations were accompanied by an increase in p110α and pAkt expression. Furthermore, Akt inhibition by LY294002 treatment restored the CDDP cytotoxicity that was suppressed by FOXO1 overexpression. FOXO1 inhibits CDDP-induced apoptosis in gastric cancer cells via activating PI3K/Akt pathway. Thus, FOXO1 may be an useful pharmacological indicator to predict CDDP efficacy in gastric cancer treatment.
    Gastric Cancer 11/2013; · 3.99 Impact Factor
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    ABSTRACT: Objectives: The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma. Methods: Two independent cohorts, a training set (n = 524) and validation set (n = 394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray. Results: ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival. Conclusions: This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.
    Pathobiology 08/2013; 81(1):25-35. · 1.95 Impact Factor
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    ABSTRACT: This aim of this study was to evaluate the relationship between hexokinase II expression and chemoresistance in epithelial ovarian cancer. One hundred and eleven paraffin-embedded specimens from patients with epithelial ovarian cancer were immunohistochemically stained for hexokinase II. Subsequently, the association between hexokinase II overexpression and clinicopathologic characteristics including chemoresistance was assessed. Survival analyses were also performed for evaluating the prognostic value of hexokinase II overexpression. Tumor recurrence within 6 months after termination of first-line chemotherapy was considered to indicate chemoresistance. Hexokinase II overexpression was associated with chemoresistance (p = 0.029) and was an independent risk factor for chemoresistance [odds ratio (OR) 3.37; 95 % confidence interval (CI) 1.07-10.62; p = 0.038] along with non-optimal debulking surgery (OR 4.93; 95 % CI 1.43-16.98; p = 0.011). Hexokinase II overexpression was significantly associated with decreased progression-free survival (p = 0.002) and showed a similar trend for overall survival (p = 0.101). Cox regression analysis revealed that hexokinase II overexpression was an independent prognostic factor for early recurrence (hazard ratio 2.63; 95 % CI 1.40-4.92; p = 0.002). Our findings suggest that hexokinase II overexpression is associated with short progression-free survival, which could be associated with chemoresistance in epithelial ovarian cancer.
    Clinical and Experimental Medicine 08/2013; · 2.83 Impact Factor
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    ABSTRACT: AIM OF THE STUDY: Valproic acid (VPA) has been known to reduce neuronal injury, have anti-inflammatory and anti-apoptotic effects as a histone deacetylase (HDAC) inhibitor. Thus, this study was performed to investigate the effects of VPA on survival and neurological outcomes in an asphyxial cardiac arrest model of rats. METHODS: Male Sprague-Dawley rats were subjected to asphyxial cardiac arrest. For survival study, rats were subjected to 450seconds of asphyxial cardiac arrest. Cardiopulmonary resuscitation (CPR) was performed and then rats were blindly allocated to one of two groups (control group, n=10; VPA group, n=10). Valproic acid (300mg/Kg) or vehicle (normal saline) was administered via tail vein immediately after return of spontaneous circulation (ROSC) and observed for 72hours. For neurological outcome study, rats (n=7 for each group) were subjected to same experimental procedures except duration of cardiac arrest of 360seconds. Neurological deficit scale (NDS) score was measured every 24hours after ROSC for 72hours and was ranged from 0 (brain dead) to 80 (normal). Brain tissues were harvested at 72hours for evaluation of apoptotic injury and acetylation status of histone H3. RESULTS: In survival study, 2 rats in VPA group were excluded because cardiac arrest was not achieved in predetermined time. Thus, 10 rats were allocated to control group and 8 rats were allocated to VPA group. The survival rates at 72hours after cardiac arrest were significantly higher in VPA group than in control group (6/8 in VPA group, 3/10 rats in control group; log rank test, p<0.05). In neurological outcome study, all rats survived for 72hours and NDS at 72hour were significantly higher in VPA group than in control group (p<0.05). In brain tissues, expressions of acetylated histone H3 were not significantly different. However, expressions of cleaved caspase-3 were significantly lower in VPA group than in control group (p <0.05). CONCLUSION: VPA increased survival rates and improved neurologic outcome in asphyxial cardiac arrest model of rats while decreasing expressions of cleaved caspase-3.
    Resuscitation 05/2013; · 4.10 Impact Factor
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    ABSTRACT: The prognostic significance of ataxia-telangiectasia mutated (ATM) expression in gastric cancer remains unclear. The functional loss of the ATM gene exhibits a biologic correlation with microsatellite instability (MSI). In this study, we investigated the significance of ATM expression with MSI by evaluating gastric cancer patients who had undergone curative resection. ATM expression was classified into low ATM expression (-,+/-,+) and high ATM expression (++,+++) using immunohistochemistry analysis. MSI status was classified as MSI-negative (MSS, MSI-Low) and MSI-positive (MSI-High). Of 321 patients, 205 (63.9%) exhibited low ATM expression and 116 (36.1%) exhibited high ATM expression. Low ATM expression was more frequently identified in patients of older age, more advanced stage, and with MSI-positive tumor (p=0.025, p=0.001, and p=0.014, respectively). The probability of 5-year disease-free survival (DFS) and overall survival (OS) was lower in low ATM expression group compared to the high ATM expression group (DFS: 62.5%, 76.4%, p=0.017, OS: 65.9%, 78.5%, p=0.027, respectively). According to MSI status, a subgroup of MSI-negative and low ATM expression cases exhibited the worst prognosis for DFS and OS; this subgroup also exhibited poorer DFS according to multivariable analysis (HR=1.8, 95% CI, 1.2-2.8, p=0.010), although prognostic value of ATM expression alone did not remain in the multivariable analysis. Taken together, these findings indicate that ATM expression with MSI status is an independent factor for gastric cancer prognosis in gastric cancer patients who received curative surgery. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2013; · 6.20 Impact Factor
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    ABSTRACT: BACKGROUND: We aimed to investigate the role of BRCA1 nuclear expression in sporadic gastric cancer; currently, the role remains unknown. METHODS: Patients with gastric cancer who received curative operation with D2 dissection were enrolled in this study. Adjuvant chemotherapy was administered at the discretion of the physician. According to BRCA1 nuclear expression analysis by immunohistochemistry (IHC) on tissue microarrays using anti-BRCA1 antibody MS110, BRCA1 expression was classified as negative, low expression, and high expression. RESULTS: Among 318 cases, 155 cases (48.7 %) were identified as BRCA1-negative by IHC and 96 cases (30.2 %) revealed BRCA1 low expression, 67 cases (21.0 %) showed BRCA1 high expression. The negative or reduced expression of BRCA1 was more frequent in more advanced-stage disease (p < 0.001) and was associated with perineural invasion (p = 0.032). Disease-free survival (DFS) was significantly decreased with reduced BRCA1 expression (p = 0.027). This tendency was also observed in overall survival (OS), although the difference was not significant. The poorer prognosis of BRCA1-negative tumors was overcome through adjuvant chemotherapy. The benefit of adjuvant chemotherapy for DFS and OS in stage III was enhanced only in BRCA1-negative tumors (p < 0.001, p < 0.001, respectively), but not in BRCA1-positive tumors (p = 0.236, p = 0.148, respectively). CONCLUSION: The reduction of BRCA1 nuclear expression is associated with advanced stage and perineural invasion. Moreover, negative BRCA1 nuclear expression is a predictive marker regarding the benefit of adjuvant chemotherapy in sporadic gastric cancer; these novel findings are of great importance, and further, larger studies are warranted.
    Cancer Chemotherapy and Pharmacology 04/2013; · 2.80 Impact Factor
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    ABSTRACT: ATM (ataxia telangiectasia mutated) is one of several DNA repair proteins that are suggested to sensitize tumor cells to the poly(ADP-ribose) polymerase inhibitor olaparib when deficient. The aim of this study was to assess the spatiotemporal concordance of ATM immunohistochemistry (IHC) in gastric cancer in order to determine if measurements made at the level of various sample types and times could be inferred as having the potential to be relevant to treatment decisions made at the patient level. Two independent cohorts composed of 591 gastric cancer patients divided into a gastrectomy cohort (n = 450) and a metastasis cohort (n = 141) were used in this study. A total of 2,705 ATM IHC samples were examined, including 450 whole tissue, 3 sets of 450 tissue microarray (TMA), 301 biopsy, 222 metastatic tumor and 2 additional whole tissue samples of 50 cases from the gastrectomy cohort, and 141 pairs of primary and metastatic tumors from the metastasis cohort. The prevalence of ATM negativity was 13.1% in biopsies, 13.9, 15.1, and 16.0% in TMAs and 15.9% in whole tissue samples of the gastrectomy cohort, and 21.4% in primary tumor and 21.5% in metastatic tumor samples of the metastasis cohort. coefficients were 0.341 for biopsy, 0.572 as the average of 3 TMAs and 0.415 for the largely synchronous metastatic tumors of the gastrectomy cohort, and 0.153 for the largely asynchronous metastatic tumors of the metastasis cohort. Using whole tissue sections from tumor resections or primary tumor, respectively, as the reference standards, specificity and sensitivity were 91.6 and 41.0% for biopsy, 93.9 and 61.9% as the average of 3 TMAs, and 86.6 and 58.8% for metastatic tumors of the gastrectomy cohort and 81.7 and 33.3% for metastatic tumors of the metastasis cohort, respectively. Although we have demonstrated that the IHC assay for ATM was robust and reproducible in gastric tumor samples, we have also found that measurements were subject to significant discordance across multiple sample types from the same patient. Further work will be necessary to determine if classification may be made more consistent by multiple sampling. However, the lack of agreement between primary and asynchronous metastatic samples suggests that such sampling would need to be performed at the time of any treatment decision.
    Pathobiology 01/2013; 80(3):127-137. · 1.95 Impact Factor
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    ABSTRACT: The transcription factor nuclear factor-κB (NF-κB) has been implicated in gastric cancer metastasis, but the underlying molecular mechanisms remain unclear. We investigated the role of the interaction between NF-κB and signal transducers and activators of transcription 3 (STAT3) in controlling metastatic potential of gastric cancer cells. Immunohistochemistry for NF-κB p65 (RelA), phospho-Tyr705-STAT3 (pSTAT3), or matrix metalloproteinase 9 (MMP9) was performed on tissue array slides containing 255 gastric carcinoma specimens. NF-κB inhibition in SNU-638 and MKN1 gastric cancer cell lines were performed by transduction with a retroviral vector containing NF-κB repressor mutant of IκBα, and STAT3 was silenced by RNA interference. We also did luciferase reporter assay, double immunofluorescence staining and immunoblotting. Cell migration and invasion were determined by wound-healing assay and invasion assay, respectively. NF-κB and STAT3 were constitutively activated and were positively correlated (P = 0.038) in gastric cancer tissue specimens. In cell culture experiments, NF-κB inhibition reduced STAT3 expression and activation, whereas STAT3 silencing did not affect NF-κB activation. Moreover, both NF-κB inhibition and STAT3 silencing decreased gastric cancer cell migration and invasion in a synergistic manner. In addition, both NF-κB activation and STAT3 activation were positively correlated with MMP9 in gastric cancer tissues (P = 0.001 and P = 0.022, respectively), decreased E-cadherin expression and increased Snail and MMP9 expressions in cultured cells. NF-κB and STAT3 are positively associated and synergistically contribute to the metastatic potential of gastric cancer cells. Thus, dual use of NF-κB and STAT3 inhibitors may enhance the efficacy of the anti-metastatic treatment of gastric cancer.
    BMC Gastroenterology 01/2013; 13:29. · 2.11 Impact Factor

Publication Stats

931 Citations
330.13 Total Impact Points

Institutions

  • 2005–2014
    • Seoul National University Hospital
      • • Department of Pathology
      • • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2012–2013
    • Seoul National University
      • • Department of Anatomy
      • • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2011
    • Cancer Research Institute
      New York City, New York, United States
  • 2009
    • Dongguk University
      • Department of Pathology
      Seoul, Seoul, South Korea
  • 2007
    • Seoul National University Bundang Hospital
      • Department of Pathology
      Seoul, Seoul, South Korea
  • 2004
    • Research Institute of Ophthalmology
      Al Qāhirah, Al Qāhirah, Egypt