Analysis of the Survival Period in Resectable Stage IV Gastric Cancer

Background: Patients with stage IV gastric cancer usually have a poor prognosis, but some patients with resectable cancer survive for more than 5 years. We aimed to study the correlation of protein expression and survival in resectable stage IV gastric cancer.Patients and Methods: Tissue samples of 42 patients with resectable stage IV gastric cancer were stained immunohistochemically for the mutant p53 protein and heat shock protein-27 (hsp27). The correlation between protein expression and clinicopathological factors was investigated. Furthermore, prognostic value of each factor was analyzed.Results: Univariate analysis showed that pN factors (Japanese classification, P = .028; International Union Against Cancer classification, P = .024), blood vessel invasion (P = .043), hsp27 overexpression (P = .019), and the index of p53 and hsp27 overexpression (P = .0026) had a prognostic influence. Only Lauren classification, however, revealed the prognostic influence in multivariate analysis (P = .046).Conclusions: These results suggest that immunostaining of tumor specimens for p53 and hsp27 and clinicopathological analysis may help predict the survival of patients with resectable stage IV gastric cancer.     

Cytoplasmic CD24 Expression Is a Novel Prognostic Factor in Diffuse-Type Gastric Adenocarcinoma

Background CD24, a mucin like cell surface adhesion molecule and a ligand for P-selectin, has been reported as a prognostic factor in a variety of human cancers. However, the role of CD24 in gastric adenocarcinoma remains largely unknown. Methods The expression pattern of CD24 in 103 gastric adenocarcinomas (31 diffuse type, 60 intestinal type, and 12 mixed type) was analyzed by immunohistochemistry. Results Cytoplasmic CD24 expression occurred in 50% of the gastric adenocarcinoma patients and was associated with high-stage tumor (Stage III–IV, P = .023), serosal invasion (SI, P = .010), lymphovascular invasion (LVI, P = .039), and lower 10-year survival (P = .0238). The CD24 staining pattern was different in intestinal and diffuse-type gastric adenocarcinomas. However, the tumor thrombi in lymphovascular spaces exhibited strong cytoplasmic CD24 expression in both types. Further analysis showed that cytoplasmic CD24 expression was, in fact, correlated with high-stage tumor, SI, LVI, and lower 10-year survival significantly (P = .020, P = .007, P = .018, P = .0285, respectively) in diffuse-type gastric adenocarcinoma. Moreover, multivariate analysis showed that cytoplasmic CD24 expression was an independent risk factor of SI and LVI respectively (P = .0083 and P = .0019), and thus it contributed to high-stage tumor and poor patient survival in diffuse- or mixed-type gastric adenocarcinoma. Conclusions Cytoplasmic expression of CD24 was associated with invasiveness and poorer prognosis and can serve as a novel target for prognostic prediction and adjuvant treatment of patients with diffuse-type gastric adenocarcinoma after tumor resection.     

Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance

Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.     

FBXO43在胃癌中的表达及其生物学功能与作用机制

背景与目的：F-BOX蛋白（FBP）家族成员F-box only protein 43 (FBXO43）在肝癌和结直肠癌等消化系统肿瘤中高表达,促进肿瘤恶性进展,且研究显示,FBXO43促进p53降解,发挥促瘤功能。为此本研究进一步探讨FBXO43在胃癌中的表达及其在胃癌恶性进展中的功能与相关机制。方法：基于TCGA、GTEx和Kaplan-Meier Plotter等在线数据库,分析FBXO43在胃癌组织中的表达及其与胃癌患者预后的相关性。用Western blot和qPCR检测FBXO43在胃癌细胞与正常胃黏膜上皮细胞中的表达水平;用免疫组化检测在胃癌组织与癌旁组织中FBXO43的蛋白水平。利用脂质体转染特异性靶向FBXO43和p53的小分子干扰RNA分子（siFBXO43和sip53）,分别或同时敲低HGC27和MGC803细胞中的FBXO43和p53的表达,利用CCK8、平板克隆形成、Transwell侵袭和迁移等实验,检测细胞生长、增殖、迁移和侵袭能力的影响;利用免疫共沉淀（Co-IP）检测FBXO43和p53的相互作用情况,以及敲低FBXO43后,p53的总泛素化水平。结果...     

Expression of p53 and RB Proteins in Squamous Cell Carcinoma of the Esophagus: Their Relationship With Clinicopathologic Characteristics

Background: Cancer of the esophagus is one of the most malignant tumors and has a poor prognosis. The p53 and retinoblastoma (RB) genes are involved in the regulation of cell population by suppressing cell proliferative activity. Our goal was to clarify whether expression of p53 and RB genes could be prognostic factors in squamous cell carcinoma of the esophagus.Methods: Tumor samples taken from 73 patients undergoing subtotal esophagectomy were immunohistochemically stained for the p53 and RB genes. An image analyzer was used for quantitative assessment of the staining, and clinicopathologic characteristics of those patients were investigated.Results: Patients in whom p53 expression was high had greater tumor diameter, deeper tumor invasion, and worse prognosis compared with patients in whom p53 expression was low. Patients in whom RB expression was low had a higher incidence of lymph node metastasis and more advanced disease than did those in whom RB expression was high. The combination of p53 and RB expression revealed that the cases with high p53 and low RB expression had significantly worse survival rates and deeper tumor invasion compared with other groups. In various clinicopathologic parameters, (e.g., age, sex, tumor-diameter, tumor type, location, differentiation, TNM classification,TNM stage) tumor type, tumor size, depth of invasion, lymph node involvement, distant metastasis, and combined p53 and RB expression showed significant differences in survival by univariate analysis. Among those six variables, only lymph node involvement showed an independent prognostic factor for survival (P = .0055) by multivariate analysis.Conclusions: The combination of p53 and RB expression is not a prognostic indicator in the surgical treatment of esophageal cancer.     

Lymph node metastasis as a significant prognostic factor in early gastric cancer: Analysis of 1,136 early gastric cancers

Background: Gastric cancer is the most frquent cancer and the leading cause of death from cancer in Korea. Early gastric cancer has been defined as a gastric carcinoma confined to mucosa or submucosa, regardless of lymph node status, and has an excellent prognosis with a >90% 5-year survival rate. From 1974 to 1992, we encountered 7,606 cases of gastric cancer and performed 6,928 gastric resections. Among them, 1,136 cases were early gastric cancer (14.9% of all gastric cancer cases and 16.4% of resected gastric cancer cases). Methods: A retrospective analysis of 1,136 cases of early gastric cancer was performed to evaluate the prognostic significance of clinicopathologic features (sex, age, tumor location, gross type, histologic type, depth of invasion, status of lymph node metastasis, resection type). Lymph node metastasis was classified into three groups: N(n=0) for no lymph node metastasis; N(n=1–3) for one to three lymph node metastases; and N(n>3) for more than three lymph node metastases. All patients received radical total or subtotal gastrectomy with lymph node dissection. Results: In univariate and multivariate analysis of these nine factors, the only statistically significant prognostic factor was regional lymph node metastasis (p<0.001). The others had no statistically significant association with prognosis. Lymph node metastasis was present in 178 cases (15.7%). The factors associated with the lymph node metastasis were depth of invasion and gross type [protruding type (e.g., types I, IIa)]. One hundred twenty-five of these patients had one to three lymph node metastases, and 53 cases had more than three lymph node metastases. The difference in 5-year survival rates among these groups was statistically significant: 94.5% for N(n=0), 88.3% for N(n=1–3), and 77.3% for N(n>3). Conclusion: We propose that for early gastric cancer, lymph node dissection is necessary in addition to gastric resection, at least in patients with a high risk of lymph node metastasis.     

Clinicopathologic significance of Her-2 and P53 expressions in gastric cancer

BackgroundTo detect the expression of HER-2 and P53 patients with gastric cancer and to analyze their correlation.MethodsA total of 249 gastric cancer patients with complete clinical data who received surgical treatment from China–Japan Union Hospital of Jilin University were selected. The expression of Her-2 and P53 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between HER-2 and P53 in gastric cancer were analyzed.ResultsThe positive rate of Her-2 and P53 expression was 37.3% (93/249) and 100% in all the specimens, respectively. The intensity of Her-2 expression was significantly different in patients with different degrees of gastric cancer cell differentiation (P = 0.012). Meanwhile, the expression of her-2 was closely related to whether the pathological type of gastric cancer was a signet-ring cell carcinoma (P = 0.022). Different percentage of positive P53 expression was closely related to the grade of tumor differentiation (P = 0.035) and positive Ki67 expression (P = 0.001). There was a significant positive correlation between HER-2 and P53 expression in gastric cancer (P = 0.003). These findings suggest that HER-2 and P53 have synergistic effects in gastric cancer.ConclusionHer-2 and P53 are important markers for invasion and metastasis of gastric cancer. Combined detection of P53 and Her-2 expression in gastric cancer tissue can be used to assess prognosis and screen cancer patients at high risk of metastasis.     

Prognostic Significance of p53 and Ki67 Proteins Expression in Greek Gastric Cancer Patients

Aim: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. Materials and methods: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. Results: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival.

Conclusions: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.     

p53、bcl-2和nm23基因在胃癌组织中的表达及其临床意义

目的　研究胃癌组织中bcl 2、p5 3和nm2 3基因的表达及其与临床病理的关系 ,探讨bcl 2、p5 3和nm2 3基因与胃癌生物学行为的相关性。方法　采用免疫组化方法对 80例胃癌组织、3 7例不典型增生癌旁组织及 2 0例正常胃粘膜组织中的bcl 2、p5 3和nm 2 3基因的表达情况进行检测。 结果　bcl 2蛋白在胃癌癌旁轻、中、重度不典型增生组织中的表达阳性率分别为 7.1%、18.1%和 2 5 .0 % ,其在各组间表达的差异无统计学意义 (P>0 .0 5 ) ,bcl 2蛋白在高分化胃癌组织中的表达阳性率为 78.2 % ,明显高于在低分化胃癌组织中的表达 (4 8.5 % ,P<0 .0 5 )。p5 3在高分化胃癌组织中的表达阳性率为 72 .5 % ,明显低于低分化胃癌组织的 86.2 % (P<0 .0 5 )。nm 2 3在高分化胃癌组织中的表达阳性率为84.3 % ,明显高于低分化胃癌组织的 17.2 % (P<0 .0 5 )。伴有淋巴结转移的胃癌组织中nm 2 3的表达阳性率为 5 4.5 % ,低于无淋巴结转移者的表达阳性率 (85 .7% ,P<0 .0 5 )。p5 3与bcl 2在胃癌组织中的表达呈明显负相关。结论　bcl 2、p5 3和nm 2 3的表达与胃癌细胞的分化程度密切相关 ,对患者预后有重要参考价值。     

突变型p53与Nampt在胃癌组织中的表达及其与预后的关系

目的：探讨突变型p53（mutp53）和尼克酰胺磷酸核糖转移酶（Nampt）在胃癌组织中的表达及其对患者预后的影响。方法：用免疫组化法检测68例胃癌患者胃癌组织及癌旁正常胃黏膜组织中p53（免疫组化检测到的p53主要为mutp53）与Nampt的表达,分析mutp53与Nampt表达与患者临床病理因素及预后的关系。 结果：胃癌组织中mutp53与Nampt的阳性表达率均明显高于癌旁正常胃黏膜组织（均P<0.05）;mutp53的高表达与肿瘤大小、浸润深度、淋巴结转移及TNM分期有关,而Nampt的高表达与肿瘤浸润深度、淋巴结转移及TNM分期有关（均P<0.05）。胃癌组织中,p53表达与Nampt表达呈明显正相关（r=0.982,P<0.05）。p53阳性表达患者的中位生存期明显短于阴性表达患者,且在p53阳性表达患者中,Nampt同时阳性患者的中位生存期明显短于Nampt阴性患者（均P<0.05）。结论：mutp53与Nampt的表达均与胃癌的恶性生物学行为相关,且两者存在一定的关联性,同时高表达患者预后差。

     

Protein Expression of bax, bcl-2, and p53 in Patients with Non-Hodgkin's Gastric Lymphoma: Prognostic Significance

The biologic significance of bcl-2, bax, and p53 gene expression in patients with non-Hodgkin's gastric lymphoma is unknown. We examined the prognostic value of these genes in 36 patients with gastric lymphoma treated in our clinic between 1990 and 1995. Paraffin-embedded specimens from 36 patients who underwent primary resection of the stomach for gastric lymphoma were analyzed immunohistochemically for p53, bax, and bcl-2 gene expression. Expression of bax was seen in 24 of 36 patients (66.7%), p53 expression was found in 8 of 36 tumors (22.2%), and bcl-2 cytoplasmic staining was detected in 6 of 36 patients (16.7%). We performed a univariate analysis to examine the possible correlation between the expression of these genes and the survival of our patients. Expression of bax protein proved to be a statistically significant prognostic factor (p= 0.049). Protein expression of p53 and bcl-2 did not statistically correlate with survival. In the bcl-2-negative (−) patient group (30 patients), those who were bax-positive had a statistically significant better survival than those who were bax-negative (63.3% vs. 36.7%, p= 0.03). There was also a statistically significant correlation between p53 expression and the grade of the tumor (p= 0.0014). P53 protein expression increased along with the grade. Expression of bax is a significant prognostic factor in patients with gastric lymphoma. Its prognostic value increases significantly when studied in bcl-2-negative patients; but expression of bax failed to be an independent prognostic factor. Expression of bcl-2 and p53 has no prognostic significance. Expression of p53 seems to represent a marker for loss of differentiation.     

Genomic and epigenetic profiles of gastric cancer: Potential diagnostic and therapeutic applications

Knowledge about the molecular profile of tumor tissues is crucial to effectively target cancer cells, because cancer is a genetic disease that involves multiple genetic and epigenetic alterations. Prominent aberrations include gene mutation, amplification, loss or deletion, as well as epigenetic alterations of the promoter DNA CpG islands. All of these aberrations can lead to dynamic changes in cancer cells, as demonstrated using resected tumor samples. There are two distinct pathological types of gastric cancer: the diffuse type and the intestinal type of gastric cancer. Diffuse type gastric cancer harbors aberrations in the FGFR2/ErbB3/PI3 kinase pathway, while intestinal type gastric cancer has an activated ErbB2 oncogenic pathway. On the other hand, the prometastatic oncogene PRL-3 is commonly activated in both types of advanced gastric cancer, and might represent a relevant therapeutic target for gastric cancer with lymph node metastasis or peritoneal dissemination. Numerous tumor suppressor genes can inhibit such oncogenic pathways, and DNA methylation in CpG islands of gene promoters is frequently found to suppress the expression of such genes in gastric cancer. Helicobacter pylori infection in normal gastric mucosa may cause p53 mutations through activation of activation-induced cytidine deaminase (AID) and/or promoter DNA methylation of E-cadherin, an initiator of gastric cancer, and such abnormalities are found even in the precancerous stage of gastric carcinogenesis. In addition, it has been demonstrated that there are highly relevant methylation genes involved in cancer (HRMGs) that exhibit very frequent cancer-specific methylation in gastric cancer. Such genes are potential targets for cancer treatment, and might also serve as biomarkers of gastric cancer for either the diagnosis or for determining the prognosis or the response to treatment.     

Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

Carcinomatous Lymphatic Invasion in Early Gastric Cancer Invading Into the Submucosa

Background: Lymphatic invasion is a risk factor for lymph node metastases in patients with gastric cancer. No studies have been reported, however, on the correlation between lymphatic invasion and lymph node metastasis in early gastric cancer invading into the submucosa.Methods: We performed a retrospective analysis of lymphatic invasion in 170 patients with early gastric cancer invading into the submucosa.Results: Lymphatic invasion was found in 76 patients. Lymphatic invasion correlated significantly with the presence of lymph node metastasis and vascular invasion (P < .05) and with the degree of cancerous submucosal involvement (P < .05). The presence of lymph node metastasis also correlated with the grade of submucosal invasion and lymphatic invasion. The 5-year survival of patients with lymphatic invasion was poorer than that of patients without lymphatic invasion (P < .05). Node-negative patients had similar survival, regardless of the presence of lymphatic invasion. All patients with severe lymphatic invasion had sm3 invasion and lymph node metastases.Conclusion: Although lymphatic invasion is the first stage of lymph node metastasis, lymphatic invasion in itself does not have clinical importance except for severe invasion in early gastric cancer. It is possible to predict lymph node metastases from the combined evaluation of degree of lymphatic invasion and submucosal involvement of the tumor in patients with early gastric cancer invading into the submucosa.     

Analysis of early (pT1) gastric cancer with submucosal invasion: surgical management and possibility to schedule less invasive surgery

Background: Early gastric cancer (EGC) is one of the popular targets of less invasive surgery. The aim of the present study is to clarify the possibility of scheduling a less invasive surgery for EGC cases with submucosal (SM) invasion.Methods: Eighty cases of EGC with SM invasion were analyzed clinicopathologically and immunohistochemically. Correlations between factors that reflect cancer progression and data from endoscopic examination were investigated.Results: Thirteen cases (16.3%) showed lymph node metastasis and the numbers of metastasis-positive lymph nodes ranged from 1 to 18. Two cases showed lymph node metastasis not only in the perigastric area, but also along the left gastric artery and the common hepatic artery. Only the tumor size showed a significant correlation with lymph node metastasis (P = .014) using the data from preoperative endoscopic examination. With respect to p53 overexpression, there was no significant correlation with pathologic factors in EGC with SM invasion. The simple protuberance types that were <2 cm in diameter had no lymph node metastasis.Conclusions: It seems difficult to predict the progression of EGC with SM invasion from the data currently obtained by preoperative endoscopic examination. It was suggested that less invasive surgery could be scheduled only for simple protuberance type cases that were <2 cm in diameter. Radical gastrectomy and D2 lymph node dissection is required, in open surgery or laparoscopic surgery, for any other type of EGC with SM invasion.     

Clinical Significance of Nuclear p53 Protein Accumulation in Bladder Cancer

Objectives: To investigate the correlation of nuclear p53 accumulation with disease outcome in a cohort of patients with transitional cell carcinoma of the bladder. Methods: A total of 90 patients (11 female, 79 male) with transitional cell carcinoma of the bladder were included in this study. Tumour samples from the primary tumour were analysed by immunohistochemistry for nuclear accumulation of p53 protein. Outcome of each patient was recorded and investigated for a possible relation with p53 status. Results: Nuclear p53 deposition was determined in 22 specimens. The nuclear p53 deposition was seen in less than 20% of the nuclei examined in 13 and more than 20% in 9 cases. No stromal staining was observed. Nuclear p53 deposition was present in 15.2% (7/46) of grade 2 tumours, and 34% (15/44) of grade 3 tumours (p=0.037). Stage distribution revealed 15.5% (5/33) positivity in stage pTa, 25.8% (8/31) in pT1 and 34% (9/26) in stage pT2–3 tumours. Tumours with p53 nuclear accumulation had a higher rate of recurrence and progression and shorter survival. Conclusion: Results of the current study indicate p53 as an important factor in determination of biological behaviour of bladder cancer.     

Nonpalliative Surgical Resection for Gastric Cancer Patients with Distant Metastasis

ABSTRACT

Objective: The purpose of this study was to determine the influence of clinicopathological and treatment factors on survival in gastric cancer patients with distant metastasis after gastrectomy. Methods: From 1990 to 2002, 111 gastric cancer patients with distant metastasis underwent nonpalliative gastrectomy at the Department of Surgery, Ruijin Hospital, China. Variables including demographic data, clinicopathological characteristics, and type of surgery were analyzed for survival by using univariate and multivariate methods. Results: The median overall survival for all patients was 11.8 months. The overall survival at one-, three-, and five-year was 48.5%, 12.4%, and 5.8%, respectively. Univariate analysis demonstrated that five-year survival of patients without liver metastasis was significantly longer than that of those with liver metastasis (5.3% versus 0%, p = .006). But, multivariate analysis showed that the status of liver metastasis, as well as the other variables including gender, age, location of tumor, Borrmann type, depth of tumor invasion, lymph node involvement, peritoneal dissemination, number of metastatic sites, pathological differentiation, and types of gastrectomy, was not an independent prognostic factor associated with survival. Conclusions: Long-term survival for gastric cancer patients with distant metastasis is very poor after gastrectomy. The multivariate analysis failed to determine the independent factors of improved survival. So, only highly selected candidates should be considered for management with surgical resection.     

MiRNA-199a-3p in Plasma as a Potential Diagnostic Biomarker for Gastric Cancer

Background

MicroRNA (miRNA) has been shown the potential of cancer diagnosis. We investigated whether plasma miRNA expression could discriminate between patients with and without gastric cancer.

Methods

This study was divided into three steps: (1) miRNA microarray profiling on plasma samples from 20 gastric cancer patients and 20 healthy controls; (2) miRNA selection by real-time qRT-PCR on 30 pairs of plasma from patients and controls; and (3) qRT-PCR validation on an independent set of plasma from 180 gastric cancer patients, 80 healthy controls, and 20 patients with gastric precancerous diseases.

Results

Of the 959 human miRNAs analyzed by microarray, 37 up-regulated miRNAs and seven down-regulated miRNAs were found in gastric cancer plasma. Of the seven discrepant miRNAs validated on the plasma from 30 gastric cancer patients and 30 healthy controls, both miRNA-199a-3p and miRNA-151-5p were significantly elevated (p < 0.05) and were significantly reduced after surgery (p < 0.05) in gastric cancer patients. Further large-scale validation showed that these two miRNAs expressions in plasma were significantly higher in gastric cancer patients than healthy controls and patients with gastric precancerous diseases, respectively. However, only the expression of miRNA-199a-3p in plasma was significantly associated with tumor invasion and with lymph node metastasis and tumor, node, metastasis stage. This marker yielded an area under the receiver operating characteristic curve area of 0.837 with 80 % sensitivity and 74 % specificity in discriminating gastric cancer patients from healthy controls. In gastric cancer tissue, miRNA-199a-3p was expressed in the cytoplasm of tumor cells.

Conclusions

miRNA-199a-3p in plasma could be a novel potential diagnostic biomarker for gastric cancer detection.

     

Clinical Significance of DNA Ploidy Pattern in Stage III Gastric Cancer

p value and Hazard ratio of the DNA ploidy patterns were 0.001 and 2.099, respectively. Consequently, it was a valuable independent prognostic factor that could be used in addition to lymph node metastasis and depth of invasion. For the most advanced subclass of stage III gastric cancer the 5-year survival rate of patients with a diploid tumor was significantly higher than that for those with aneuploid tumor. No difference was observed for the other subclasses. These results indicate that the DNA ploidy pattern is a valuable independent prognostic factor for gastric cancer, and that it is more useful for evaluating the prognosis of patients with more advanced lesions undergoing “curative resection.”     

Dual Roles of Peptic Ulcer in the Carcinogenesis or Extension of Early Gastric Cancer

Background: Early gastric cancer (EGC) often coexists with peptic ulcer. In this study we investigated the roles of peptic ulcer in the carcinogenesis and extension of gastric cancer.Methods: The clinicopathological characteristics of EGC and peptic ulcer and their relationship, as well as that of the background intestinal metaplasia, were compared among the following three groups: patients with peptic ulcer only inside the EGC (Contained group, 53 patients); patients with peptic ulcer only outside the EGC (Separate group, 26 patients); and patients of EGC with no peptic ulcer (Absent group, 43 patients).Results: In the Separate group, a male preponderance was observed (P = .006), and all EGCs developed in the middle or lower third of the stomach (P = .06). Most of the EGCs were an intestinal type of cancer with severe background intestinal metaplasia. Topographically, 88% of the peptic ulcers in the Separate group developed proximal to the EGC. On the other hand, in the Contained group, most EGCs developed in the middle third of the stomach with an intestinal/diffuse type ratio of 1:1. Peptic ulcers inside the EGC were significantly more shallow than those that developed outside the EGC (P = 0.008). Although the incidences of submucosal cancer were nearly the same among the three groups, the maximum cancer diameter tended to be increased in the Contained group compared to that in the Absent group, and the incidence of lymph node involvement tended to be higher in the Contained group (8%) as compared with the other two groups (4%–5%).Conclusions: These results suggest that peptic ulcer outside the EGC contributes to the development of the intestinal type of EGC, with the background of more severe intestinal metaplasia during the peptic ulcer healing processes, whereas peptic ulcer inside the EGC develops secondary to EGC and favors cancer extension and metastasis. Peptic ulcer associated with EGC can be considered to exert different biological roles in the carcinogenesis or extension of ECG according to the location of the peptic ulcer.