Clinicopathological Features Of Gastric Cancer Research Articles

CD133 expression is correlated with chemoresistance and early recurrence of gastric cancer

CD133 has been suggested to be a cancer stem cell (CSC) marker in various types of cancers. The present study assessed the relationship between CD133 expression and clinicopathological features of gastric cancer. In addition, the prognostic value of CD133 for gastric cancer was evaluated. In total, 100 advanced gastric cancer patients who received curative gastrectomy and adjuvant chemotherapy were included. CD133 expression was determined by immunohistochemistry and clinicopathological results, including survival, were analyzed. CD133 was expressed in 23% of advanced gastric cancer patients (23/100). CD133 expression was significantly associated with serosal exposure (P = 0.036), venous invasion (P = 0.047), well and moderate differentiation (P = 0.002), and intestinal-type Lauren classification (P = 0.001). CD133-positive patients had a significantly worse 5-year disease-free (28.1% vs. 65.8%, P = 0.002) and overall (47.5% vs. 74.0%, P = 0.037) survival rate than those who were CD133-negative. A multivariate analysis suggested that CD133 expression significantly affected the 5-year disease-free and overall survival. CD133 may play an important role in chemoresistance and recurrence, thus representing a promising predictive marker for the prognosis of gastric cancer.

Agressivité du cancer gastrique chez le sujet jeune : mythe ou réalité ?

IntroductionAlthough gastric cancer (GC) is considered as a disease of middle-aged and elderly, 2%–15% of patients with CG are younger than 45 years and especially among women. Until now, many epidemiological and clinicopathological characteristics of gastric cancer, including risk factors, were conducted in the elderly. However, in young, only a few studies with small samples have been conducted. Within each study the results of these studies were highly variable, which may be due to low statistical power.Study purposeWe propose through this study a review of epidemiological, clinical and pathological characteristics of gastric cancer in young adults.Materials and methodsIt is a retrospective study including all patients sent to the hepato gastroenterology department of the University Hospital Hassan II for management of gastric adenocarcinoma gastric tumor between April 2001 and June 2010.We first described the demographic, clinical, endoscopic, histopathological, radiological treatments and also the outcome of gastric cancer in young patients and secondary we make a comparison with the characteristics of those over 45 years.ResultsTwo hundred and three patients were included during this period. Patients aged under 45 accounted for 25% (n=50). There was a female predominance in this group of patients (p=0.05), familial forms were not more frequent (p=0.1). The location of the tumor does not differ between the 2 age groups (p=0.07). On the histological side Linitic form was more frequent in young adult (40%, p=0.01), they had more metastatasis at diagnosis (p=0.0001), mostly of peritoneal carcinomatosis (p=0.04).ConclusionIn our study, gastric cancer remains uncommon in younger patients (25% of all gastric cancers). This frequency is certainly not explained by familial forms (only 1.5%). Linitic forms seem to be more frequent in younger patients, and carcinomatosis is much more common at diagnosis.

The expression of ARHI in pT2a and pT2b stage gastric cancer and its clinical significance

ARHI is a novel tumor suppressor gene located on chromosome 1p31. Downregulation of ARHI expression has been detected in many types of cancer. However, the effects of ARHI in gastric cancer remain unclear. The aim of this study was to identify the relationship between ARHI expression and gastric cancer clinicopathological features. In this study, 81 pT2 stage gastric cancer specimens were subclassified by pT2a and pT2b stage. ARHI mRNA and protein levels were evaluated by real-time PCR and western blot analysis, respectively. Methylation plays an important role in suppressor gene silencing. We utilized methylation-specific PCR to identify the status of CpG islands in the ARHI gene. We used immunohistochemistry to determine the expression of the protein and analyzed clinicopathological features. The levels of ARHI mRNA in gastric cancer were lower compared to normal tissues (P<0.01). Similarly, the levels of ARHI protein in the cancer specimens were lower (P<0.05). DNA hypermethylation was identified in 79.1% of gastric cancer specimens without ARHI expression. Immunohistochemistry results were significantly correlated with the pT2 category (P<0.05). The cumulative survival rate of patients with ARHI expression was significantly higher compared to those without ARHI expression (P<0.05). ARHI as a suppressor is not only an important factor in the pathogenesis of gastric cancer, but also a potential factor for tumor aggravation. ARHI expression in gastric cancer can be employed to indicate favorable prognosis for the disease.

How should we treat gastric cancer in the very elderly?

We aimed to clarify the clinicopathological features of gastric cancer in very elderly patients and to identify appropriate surgical therapy for them, focused particularly on their prognosis. Patients who underwent gastrectomy for gastric cancer in Oita University Hospital were included in this study. The patients were divided into two groups: the very elderly group (80 years or older) (E group) and the middle-aged group (ranging from 40 to 79 years) (M group). Their clinicopathological features and postoperative survival were compared. Type 3,4 macroscopic types, INFγ and number of dissected lymph nodes were significantly less in the E group than in the M group (p=0.0092, p=0.0077, p=0.0475, respectively). Overall survival and disease-free survival were shorter for the E group (p=0.0898, p=0.0566, respectively). When other cause-related deaths were considered to be lost to follow-up, there was no significant difference between the E group and the M group. Whenever radical resection is possible, surgical resection for gastric cancer, even in the very elderly, should not be denied. Nevertheless, surgeons should try to do less invasive surgery, especially for the very elderly.

FGFR2 gene amplification and clinicopathological features in gastric cancer

Background:Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear.Methods:Drug sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay and fluorescence in situ hybridisation (FISH).Results:FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members (FGFR1, 3 and 4) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2-amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period.Conclusion:FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.

Reduced FAF1 Expression andHelicobacterInfection: Correlations with Clinicopathological Features in Gastric Cancer

Background. This study aimed to investigate possible associations between FAF1 expression and aspects of gastric cancer, in particular its clinical characteristics and Helicobacter infection. Materials and Methods. RT-PCR and immunohistochemistry were used to analyze expression of FAF1 mRNA and protein in 40 gastric cancer patients. H. pylori infection was detected by three staining protocols. Results. The expression level of FAF1 mRNA was significantly lower in gastric cancer tissue than in normal gastric mucosa from the same patient (P < 0.05). FAF1 mRNA expression was significantly lower in stage IV gastric cancer than in stage I+II or IIIA+IIIB (P = 0.004) and also significantly lower in gastric cancer with distant metastasis. FAF1 mRNA expression was higher in well-differentiated cancer than in poorly-differentiated cancer (0.39 ± 0.06 versus 0.19 ± 0.06, t = 9.966, P < 0.01). FAF1 protein was detected in 15 of 40 (37.5%) cancerous tissue samples and in 29 of 40 (72.5%) corresponding normal tissue samples (P < 0.01). FAF1 mRNA expression was lower in H. pylori-positive cancerous tissue samples than in H. pylori-negative ones (P < 0.05). Conclusions. Downregulation of FAF1 expression may be related to the carcinogenesis and progression of gastric cancer, and H. pylori infection during gastric carcinogenesis may downregulate FAF1 expression.

Genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene in Chinese patients with gastric cancer

We explored a possible correlation of genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene with clinicopathologic features of gastric cancer in Chinese patients and looked for molecular markers for diagnosing gastric tumor development. Microsatellite instability and loss of heterozygosity of the PAI-1 gene locus D7S515, D7S471 and pai-1 in 50 specimens of gastric cancer and relevant pericancerous tissues were detected by PCR-single strand conformation polymorphism (PCR-SSCP) with sliver staining. Methylation-specific PCR was used to detect CpG methylation in the 5'-flanking region of the PAI-1 gene. Microsatellite instability was significantly more common in the negative than in the positive serosa infiltration group of gastric cancer (42.86 vs 2.33%). The frequency of microsatellite instability was significantly lower in the cases with lymph node metastasis than in those without metastasis (18.18 vs 2.56%); however, it was significantly higher in the low differentiation group than that in the middle or high differentiation groups (21.05 vs 0.00%). CpG methylation in the 5'-flanking region of the PAI-1 gene did not differ significantly. Microsatellite instability and loss of heterozygosity of the PAI-1 gene apparently regulates the development of gastric cancer through different pathways. Microsatellite instability could be used as a molecular marker for the development of gastric cancer. CpG methylation in the 5'-flanking region of the PAI-1 gene appears not to be involved in the development of gastric cancer.

Clinical significance of human kallikrein 12 gene expression in gastric cancer

To investigate whether the expression of kallikrein 12 (KLK12) is related to the development of gastric cancer (GC) and to determine the role of KLK12 in gastric cancer cells growth, invasion and migration. Between September 2007 and March 2008, 133 patients with histologically confirmed GC were recruited for the study. Expression of KLK12 was detected in samples from GC patients by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry. The relationship between KLK12 protein expression and clinicopathological features of GC was analyzed. The difference in 5-year survival rates between the high KLK12 protein expression group and the low KLK12 expression group was compared. Additionally, the expression of KLK12 was examined in various human GC cell lines, including MKN-28, SGC-7901 and MKN-45. Small interfering RNA (siRNA) was used to inhibit KLK12 expression in MKN-45 cells. Cell clones stably transfected with KLK12 siRNA were tested for KLK12 expression by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. Furthermore, a series of functional assays were performed in this study to assess the biological features of transfected cells. Cell proliferation was assessed using the methylthiazolyltetrazoliumassay. Finally, cell migration and invasion were assessed using transwell chamber assays. Of the 133 GC patients included in the study, 126 (94.7%) showed a higher expression level of KLK12 mRNA when compared to noncancerous tissue specimens. Expression of KLK12 mRNA was significantly higher in GC tissues than in normal tissue (P < 0.001). KLK12 protein expression was detected in 96 of 133 (72.2%) GC samples with moderate or strong staining primarily in the cytoplasm. In contrast, negative immunostaining for KLK12 protein was observed in the corresponding normal gastric mucosal tissue. Overexpression of KLK12 protein was significantly associated with lymph node metastasis (P = 0.001), histological type (P < 0.001) and tumor-node-metastasis stage (P = 0.005), while no significant correlation was observed between expression of KLK12 protein and sex, age, depth of invasion, tumor size or lymphatic invasion. Furthermore, patients with high KLK12 expression had a significantly poorer 5-year survival rate than those with low KLK12 expression (P = 0.002). Expression of KLK12 mRNA was significantly higher in MKN-45 GC cells compared to normal mucosal cells or two other GC cell lines (P < 0.01). Expression of KLK12 in MKN-45 cells was downregulated after transfection with siRNA. Knockdown of KLK12 markedly decreased the proliferation of MKN-45 cells when compared with parent or mock-transfected cells (P = 0.001), especially from the 3rd to the 5th day of the assay. In migration assays, fewer KLK12 siRNA cells migrated through the chambers (22.00 ± 1.81) when compared to the parent (46.47 ± 2.42) or mock-transfected cells (45.40 ± 1.99); these differences were statistically significant (P < 0.001). However, in the invasion assay, the number of KLK12 siRNA cells that invaded the chambers was 18.40 ± 1.12, closely similar to both the parent (18.67 ± 0.98) and mock-transfected cells (18.53 ± 0.92). There was no significantly difference between the three groups in the invasion assay (P = 0.054). The KLK12 gene is markedly overexpressed in GC tissue, and its expression status may be a powerful prognostic indicator for patients with GC. KLK12 might serve as a novel diagnosis and prognosis biomarker in GC.

Clinical significance of microRNA-199a expression in gastric cancer

Objective To investigate the expression of miR-199a-3p and miR-199a-5p and its association with clinicopathologic features in gastric cancer.Methods The expression levels of miR-199a-3p and miR-199a-5p in 32 gastric cancers and their matched non-tumor adjacent tissue specimens were detected by using stem-loop real-time reverse transcription-polymerase chain reaction (RT-PCR),and their correlation with clinicopathologic features of gastric cancer was analyzed.Results Expression levels of miR199a-3p and miR-199a-5p were significantly higher in tumor tissues than in adjacent normal tissues ( P ＜0.05 ).The expression of miR-199a-3p was associated with lymph node metastasis positively (P ＜ 0.01 ),TNM stage (P ＜0.05) and cell differentiation (P ＜0.01 ).The expressions of miR-199a-5p was associated with cell differentiation ( P ＜ 0.01 ) and location ( P ＜ 0.05 ).ROC curve of miR-199a-3p and miR199a-5p about cell differentiation resulted in a diagnostic sensitivity of 93.3％ and spectificity of 71.4％.Conclusion The level of miR-199a-3p and miR-199a-5p expression may be a valuable adjuvant parameter in forecasting the poorly differentiated gastric cancer. Key words: microRNA; Gastric carcinoma; Cell differentiation

Expression of FHL1 in gastric cancer tissue and its correlation with the invasion and metastasis of gastric cancer

This study was performed to analyze the expression of four and a half LIM domains 1 (FHL1) in gastric carcinoma tissue and its correlation with the clinicopathological characteristics of gastric cancer. In addition, the role of FHL1 in the invasion and metastasis of gastric cancer cells was investigated to provide an experimental basis for future treatments of gastric cancer. FHL1 mRNA and protein expression in gastric carcinoma and the adjacent normal gastric mucosa tissue were determined using RT-PCR and western blots. Correlations of FHL1 expression with the incidence, progression, and clinicopathological characteristics of gastric cancer were analyzed. Changes in the invasion and metastatic potential of MKN45 human gastric cancer cells were observed after the transient transfection with an eukaryotic expression vector containing full-length FHL1. Expression of FHL1 mRNA in gastric carcinoma tissue was significantly lower than that in the adjacent normal tissue (P < 0.05). FHL1 expression in gastric carcinoma tissue from patients who were positive for lymph node metastasis was significantly lower than those in patients who were negative for lymph node metastasis (P < 0.05). Lower FHL1 expression was correlated with lower degrees of differentiation, higher TNM stages, and greater invasive potential of the gastric cancer (P < 0.05). The FHL1 mRNA and protein expression patterns were similar in gastric cancer. FHL1 protein expression in gastric carcinoma tissue was significantly lower than that in the surrounding normal tissue (P < 0.05). FHL1 protein expression was significantly lower in gastric carcinoma tissue from patients who were positive for lymph node metastasis than that detected in patients with no lymph node metastasis (P < 0.05). Lower FHL1 protein expression was correlated with lower degrees of differentiation, higher TNM stages, and greater invasive potential in gastric cancer (P < 0.05). However, the expression of FHL1 was independent of the patient's gender, age, and tumor size (P > 0.05). Overexpression of FHL1 in the MKN45 human gastric cancer cell line using an eukaryotic expression vector resulted in a significant reduction in the invasiveness and metastatic ability of these cells as determined using the Transwell chamber invasion assay (P < 0.05). The decrease in or loss of FHL1 expression may be related to the incidence, progression, invasiveness, and metastatic potential of gastric cancer.

Abnormal Expression of Adhesion Protein Bves is Associated with Gastric Cancer Progression and Poor Survival

Although many molecular and biological studies have shown risk factors for gastric cancer, the available knowledge is still insufficient to unveil the exact mechanism of gastric cancer. To investigate the relationships between Bves expression and the clinicopathologic features of gastric cancer and whether Bves can act as prognostic indicators in gastric cancer. Tissues were obtained from the gastrectomy specimens of 306 human gastric cancer and 78 noncancerous gastric tissue at the Department of Surgery and Pathology, the Second Affiliated Hospital of Kunming Medical University from February 1996 to March 2007. The method of immunohistochemistry was used to investigate the expression of Bves in them. The relationship between Bves expression and the survival times of the patients was retrospectively analysed. Reduced expression of Bves frequently occurred in gastric cancer tissue. Low expression of Bves correlated with histologic differentiation, depth of invasion, regional lymph nodes and distant metastasis, and TNM stages (P < 0.05). Bves expression did not correlate with age, gender, location of tumor, size of tumor and histologic type (P > 0.05); Further multivariate analysis revealed that lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), surgical treatment (P < 0.0001), and the expression of Bves (P < 0.0001) were independent prognostic factors in patients with gastric cancer; The Kaplan-Meier plot showed that survival times of patients with low Bves expression was significantly lower than those in patients with high Bves expression. Besides, low Bves expression had a much more significant effect on the survival of those patients with early stage tumors (χ2 = 131.216,P < 0.0001), highlighted by a >51.3% reduction in 3-year survival compared with that of patients with high Bves expression. In late stages, the difference was also significant (χ2 = 5.818,P = 0.016), with a 34.8% reduction in 3-year survival. Reduced expression of Bves in gastric cancer is associated with tumor progression and the patient's poor survival. This study showed that the studied protein has further provided a basis for the development of potential biomarker for gastric cancer prognosis.

Overexpression of G6PD is associated with poor clinical outcome in gastric cancer

This study aims to investigate the expression and significance of glucose-6-phosphate dehydrogenase (G6PD) in human gastric cancer progression and prognosis. Using immunohistochemistry and real-time RT-PCR assay, we identified abnormally elevated expression of G6PD in gastric cancer tissues compared to paired normal stomach mucosa tissues in 24 patients (p < 0.05). In order to investigate the correlations between G6PD and the clinicopathological features of gastric cancer, the expression of G6PD in 167 patients with gastric cancer were detected by immunohistochemistry, and the results showed that overexpression of G6PD was associated with the size of tumor (p = 0.039), depth of invasion (p = 0.039), lymph node metastasis (p = 0.044), distant metastasis (p = 0.003), TNM stage (p = 0.030), and survival rate (p = 0.010). Further, Cox multivariates analysis indicated that G6PD expression level was an independent prognostic factor for patients after radical resection (p = 0.013). In conclusion, overexpression of G6PD is closely related to progression of gastric cancer, and might be regarded as an independent predictor of poor prognosis for gastric cancer.

Overexpression of minichromosome maintenance 2 predicts poor prognosis in patients with gastric cancer

We examined the expression of minichromosome maintenance 2 (MCM2) in gastric cancer and adjacent normal tissues and estimated the possible value of MCM2 as a novel prognostic marker. Using real-time PCR, western blotting and immunohistochemistry, we examined the expression of MCM2 in gastric carcinoma and paired normal gastric mucosa. Statistical analysis of the expression of MCM2 mRNA and protein in gastric cancer and normal tissues was performed to evaluate the relationship between MCM2 expression and clinicopathological characteristics in gastric cancer. The expression of MCM2 mRNA and protein in gastric carcinomas was significantly higher compared to that in normal gastric mucosa (P=0.04). Immunohistochemistry analysis showed that MCM2 expression was significantly up-regulated in tumor and metastastic lymph node tissues compared with the corresponding non-cancerous mucosa (P<0.05). Positive expression of MCM2 was significantly associated with patient age, T category and the presence of lymph node metastasis (P<0.05). There were no differences between MCM2 expression and gender, tumor size, tumor location, M category, International Union Against Cancer (UICC) stage, vessel invasion and tumor differentiation. Patients with negative tumor MCM2 expression displayed a better survival time than those with positive MCM2 expression (P<0.05). Survival analysis showed that positive MCM2 expression (P<0.05), T stage (P<0.05) and N stage (P<0.05) were independent prognostic factors for disease-free survival (DFS) and overall survival (OS). Our data suggest that MCM2 could serve as a novel prognostic biomarker in gastric carcinoma.

Clinicopathological observation of gastric cancer with pathological complete response following neoadjuvant chemotherapy

To observe the clinicopathological characteristics of gastric cancer with pathological complete response(pCR) following neoadjuvant chemotherapy. Data of gastric cancer patients who received neoadjuvant chemotherapy from 2002 to 2008 in the Beijing Cancer Hospital were reviewed. Five cases were found to have pCR. The slides were reviewed by two experienced pathologists independently. Histological structure, morphology of tumor cells, morphology and quantity of stromal cells were evaluated. Structure of the gastric wall was distinguishable in all the 5 cases, while distortion and rupture of muscular layer were found in 2 cases. Exudative inflammatory reaction was present in the whole gastric wall including the serosa layer. Three patients had ulcerative lesions with epithelial layer shedding, and atypical hyperplasia was found around the border of the ulcer, and vascular endothelial cells were swollen. Residual distorted necrotic tumor cells resided in 1 case only and no residual tumor cells was present in the other 4 patients. Significant hyperplasia of fibroblasts was present in 4 cases, large amount of lymphocytes infiltration in 3 cases including concurrent plasma cell infiltration in 1 case, multinucleated giant cell reaction in the muscular layer of 1 case, and foam cells aggregation in 1 case with mucinous adenocarcinoma. In addition, there were 2 cases with pCR had lymph node metastasis. For cases with pCR following neoadjuvant chemotherapy, heterogeneity of stromal cells reaction is found in previous tumor site. Furthermore, the response of primary tumor does not necessarily parallel to that of lymph nodes.

E‐selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population

Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E-selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E-selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13-7.12). C allele of E-selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E-selectin variant did not affect the protein expression. E-selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor-node-metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36-2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20-2.35, respectively). Interleukin-4 receptor (IL-4R) variant rs2107356 presented negative correlations to E-selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E-selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E-selectin protein would promote progression of gastric cancer.

The E-cadherin (CDH1) −160C&gt;A Polymorphism Associated with Gastric Cancer Among Asians But Not Europeans

E-cadherin (CDH1) is a tumor suppressor gene involved in epithelial cell-cell interactions and plays important roles in the etiology of gastric cancer. Studies reporting conflicting results on the role of -160C>A polymorphism in the CDH1 promoter region on gastric cancer risk led us to perform a meta-analysis to investigate this relationship. Thirteen published case-control studies including 2509 gastric cancer cases and 3687 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, individuals with the variant genotypes were not associated with a significant gastric cancer risk (AA vs. CC: OR = 1.04, 95% CI: 0.74-1.48; CA vs. CC: 1.02, 0.85-1.21; AA/CA vs. CC: 1.03, 0.86-1.22; AA vs. 1.03, 0.74-1.43). However, in the stratified analysis by ethnicity, significantly decreased gastric cancer risk was found among Asians in dominant model (AA/CA vs. CC: 0.84, 0.72-0.99). Further, when stratified by clinicopathologic characteristics of gastric cancer, no statistically significant result was observed for any analysis. The results suggested that the CDH1 -160C>A polymorphism may contribute to susceptibility to gastric cancer among Asians. Additional well-designed large studies will be required to validate this association in different populations.

Clinicopathologic Characteristics of Gastric Cancer Patients according to the Timing of the Recurrence after Curative Surgery

PurposeThere are few studies that have focused on the predictors of recurrence after gastrectomy for gastric carcinoma. This study analyzed the patients who died of recurrent gastric carcinoma and we attempted to clarify the clinicopathologic factors that are associated with the timing of recurrence.Materials and MethodsFrom June 1992 to March 2009, 1,795 patients underwent curative gastric resection at the Department of Surgery, Hanyang University College of Medicine. Among them, 428 patients died and 311 of these patients who died of recurrent gastric carcinoma were enrolled in this study. The clinicopathologic findings were compared between the 72 patients who died within one year after curative gastrectomy (the early recurrence group) and the 92 patients who died 3 years after curative gastrectomy (the late recurrence group).ResultsCompared with the late recurrence group, the early recurrence group showed an older age, a more advanced stage, a poorly differentiated type of cancer and a significantly higher tendency to have lymphatic invasion, vascular invasion and perineural invasion.Especially in the gastric cancer patients with a more advanced stage (stage III and IV), the early recurrence group was characterized by a significantly higher preoperative serum carcino embryonic antigen level, perineural invasion and a relatively small number of dissected lymph nodes.ConclusionsThe clinicopathologic characteristics of recurrent gastric cancer are significantly different according to the stage of disease, and even in the same stage. For the early detection of recurrence after curative surgery, it is important to recognize the clinicopathological factors that foretell a high risk of recurrence. It is mandatory to make an individualized surveillance schedule according to the clinicopathologic factors.

Clinicopathological Characteristics of Gastric Cancer and Survival Improvement by Surgical Treatment in the Elderly

It has been known that elderly patients with gastric cancer show worse general condition and higher comorbidities. Therefore, few elderly patients undergo surgery. This study was designed to determine clinicopathological characteristics of gastric cancer in elderly patients and evaluate their survival improvements by the surgical treatment. Gastric cancer patients, diagnosed at Ewha Womans University Mokdong Hospital between 2000 to 2004, were divided into two groups those aged ≥65 years vs. <65 years. Clinicopathological characteristics, incidence of postoperative complications, and survival time of patients in each group were analyzed. Total 370 patients were subjected and divided into the elderly and the younger group (55.4% vs. 44.6%). The elderly group showed higher incidences of hypertension and cardiovascular disease. Well differentiated adenocarcinoma was more frequently found in the elderly group (19.0% vs. 10.0%, p=0.025). There were no differences of operation time (242.6±70.7 vs. 257.3±83.8 min, p=0.115), postoperative hospital stays (15.8±10.6 vs. 14.7±9.8 days, p=0.361), and incidence of any complications (6.7% vs. 9.9%, p=0.309) between the two subgroups. The significant factors related with the elderly patient's survival were the tumor-node-metastasis (TNM) stage (stage I, hazard ratio [HR] 1.00; stage II, HR 1.28, 95% confidence interval [CI] 0.44-3.72; stage III, HR 4.06, 95% CI 2.08-7.92, stage IV, HR 9.78, 95% CI 4.97-19.26; p<0.001) and the treatment modality (laparoscopy, HR 1.00; open surgery, HR 3.90, 95% CI 2.43-6.26; p<0.001). The elderly patients who underwent gastric cancer surgery showed prolonged survival on TNM stage I, II, and III than those who were treated conservatively. In the elderly patients with gastric cancer, those who had received surgical treatments showed significantly higher survival rate than those who had treated conservatively. Therefore, aggressive surgical treatments should be seriously considered even for the elderly patients with gastric cancer.

Expression of c-erbB2 andp53in Curatively Resected Gastric Cancer: Correlation with Clinicopathologic Features and Prognosis

Purpose: We investigated the correlation between expression of c-erbB-2 and p53 proteins and clinicopathologic features of gastric cancer to reveal prognostic factors. Methods: 125 patient records under going curative resection for gastric carcinoma at our institution from January 2000 to June 2003 were collected. Surgical specimens embedded in paraffin block were evaluated for p53 and c-erbB-2 protein as detected by immunohistochemistry. Results: Samples from 30 cases (24.0%) of 125 patients with gastric adenocarcinomas demonstrated positive staining for c-erbB-2 and 72 patients (57.6%) showed positive nuclear staining for p53 protein. c-erbB-2 stained tumors were significantly associated with the depth of tumor invasion (P=0.022), lymph node metastasis (P=0.004) and lymphatic invasion (P=0.019). In a subgroup of patients with gastric carcinoma not exposed to serosa (n=91), expression of both c-erbB-2 and p53 significantly related with poor disease-free survival (OR=5.107) and survival (OR=4.449) in multivariate analysis. Conclusion: When patients with gastric adenocarcinoma showed expression of c-erbB-2 with p53, they were associated with aggressive pathologic features. In the subgroup of patients with gastric adenocarcinoma that did not involve serosa, expression of c-erbB-2 combined with p53 could become a predictive factor for recurrence and survival in multivariate analysis.

Clinicopathologic Significance of Gastric Adenocarcinoma with Neuroendocrine Features

PurposeComposite neuroendocrine-exocrine carcinomas are malignancies that have two distinct components residing within the same tumor: an adenocarcinomatous portion and a neuroendocrine portion. This is rare in gastric cancers; however, poorly differentiated adenocarcinomas can sometimes reveal evidence of neuroendocrine features (NEF) or be 'mixed endocrine and exocrine carcinomas'. This study aimed to review NEF in gastric adenocarcinoma and to evaluate its prognostic significance.Materials and MethodsWe selected 29 patients who were diagnosed with gastric adenocarcinoma with NEF and received gastrectomies at the Department of Surgery, Ajou University Hospital between January 2001 and December 2009. We analyzed the clinicopathologic features of gastric cancer with NEF and the prognosis associated with such tumors.ResultsThe pathologic result with respect to TNM staging of the gastric cancers with NEF were as follows: 5 cases of T1, 5 cases of T2, 10 cases of T3, and 9 cases of T4. There were 7 cases of N0, 7 cases of N1, 8 cases of N2 and 7 cases of N3. The staging of patients with NEF was higher than that of patients without NEF. Especially tumor lymphovascular invasion rate was 82.8%. The overall survival of patients with gastric cancer characterized by NEF was 73.8 months.ConclusionsPositive NEF status might be correlated with clinicopathologic parameters such as a high stage and high frequency of regional lymph node metastasis.