The significances of lymph node micrometastasis and its correlation with E-cadherin expression in pT1-T3N0 gastric adenocarcinoma

BACKGROUND: Recently, micrometastasis (MM) in the lymph node in gastric cancer has been detected by cytokeratin immunostaining. However, clinical significance of MM and its relationship with reduced expression of E-cadherin in primary lesion have not been well studied. METHODS: The 4,990 lymph nodes from 184 pT1~T3N0 patients from 1995 to 2000 at Korea University Hospital were immunostained with the anticytokeratin AE1/3 antibody for detection of micometastasis. The primary lesions were also immunostained for E-cadherin expression. RESULTS: MM in the lymph node of gastric cancer was found in 131 (2.6%) of total dissected nodes, and 31 of 184 patients (16.8%) were shown to have MM. The MM was significantly correlated with the depth of invasion, tumor size, operation method, Lauren classification, lymphovascular invasion and loss of E-cadherin expression in primary tumor. On multivariate analysis, the independent risk factors for MM were the depth of invasion and loss of E-cadherin expression. The patients with MM had significantly lower 5-year overall and disease free survival rate than those without MM. CONCLUSION: Lymph node MM in histologically node-negative gastric cancer was significantly correlated with poor 5-year survival rate. The determination of E-cadherin expression in primary gastric tumor may be useful in prediction of the MM.     

早期胃癌的浸润深度与淋巴结转移关系

目的：探讨早期胃癌的浸润深度、肿瘤大小与淋巴结转移之间的相关性。方法：收集103例外科手术切除的早期胃癌,统计不同时期早期胃癌的检出率,分析其临床及病理特点。结果：103例早期胃癌中黏膜内癌（M）31例,仅有1例（3％）淋巴结转移,黏膜下癌（SM）有63例,淋巴结转移率为17％,其中SM1：16．1％,SM2：34％,SM3：35％;肿瘤最大直径超过2cn的淋巴结转移率（20％）较直径≤2cm者（8．8％）高;肉眼类型中Ⅱ型最多见,并淋巴结转移率也最高;组织类型中高分化腺癌最多,其次为低分化腺癌;且低分化腺癌淋巴结转移率高。结论：早期胃癌的淋巴结转移与肿瘤的浸润深度、肿瘤的大小、肉眼所见及组织类型有关。     

早期胃癌淋巴结转移及临床意义

淋巴结转移是影响早期胃癌手术方式选择和预后的重要因素,对其转移规律和特点的认识及检测方法的掌握对于合理开展缩小手术至关重要。运用免疫组化和逆转录聚合酶链反应技术对早期胃癌前哨淋巴结检测不仅可以了解淋巴结站的转移特点、规律,而且可以发现微转移,从而指导术中淋巴结清扫范围而选择合理术式,避免标准根治术淋巴结清扫和扩大的手术方式对机体造成不必要的损害,减少手术创伤和术后并发症的出现,提高患者术后生存质量。     

Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer.

BACKGROUND AND OBJECTIVES: Limited operations for early gastric cancer (EGC) have been recommended based on data from lymph node (LN) metastasis detected by hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro-LN metastasis detected by cytokeratin (CK) immunostaining. Also, the correlation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated. METHODS: A total of 5,949 LNs from 160 patients with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were stained by CD. RESULTS: The incidence of LN metastasis increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro-LN metastasis increased according to the depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%). The CK-staining patterns were classified into the three subgroups (CK-negative, n = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage of CD-positive cancer cells of primary tumors in clustered type (17.2%) was significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P = 0.0036). CONCLUSIONS: The acidic protease CD may play an important role of cancer metastasis in EGC. The limited operation without lymphadenectomy should be indicated for EGC with CD-negative.     

Promoter hypermethylation of E-cadherin and its abnormal expression in Epstein-Barr virus-associated gastric carcinoma

Promoter hypermethylation of various tumor-related genes is extremely frequent in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC). To investigate the significance of the promoter methylation in EBVaGC, we focused on one of the important proteins in the carcinogenesis of the stomach, E-cadherin. Methylation-specific PCR analysis (MSP) was applied to surgically resected gastric carcinomas, together with immunohistochemistry, PCR-based analysis of mutations and allelic loss, and site-specific MSP of E-cadherin gene. By MSP, nearly all of the carcinomas showed aberrant methylation of E-cadherin promoter in EBVaGC (21/22), and the frequency of this aberration was significantly higher than that in EBV-negative gastric carcinoma (GC; 45/81; p = 0.0003). According to immunohistochemistry of E-cadherin, the frequency of abnormal staining pattern in EBVaGC (87%) was comparable to that in the diffuse type (80%), but higher than that in the intestinal type of EBV-negative GC (47%). Promoter methylation was well correlated with abnormal staining pattern in EBVaGC, but not in EBV-negative GC. Neither mutation nor allelic loss of E-cadherin was observed in EBVaGC. Methylation status of E-cadherin within each carcinoma was heterogeneous as far as examined. Thus, in addition to the known association involving p16, we determined that promoter methylation-mediated silencing of E-cadherin gene was also closely associated with the development of EBVaGC, although it becomes heterogeneous within a given tumor along its progression.     

CD44v6、E-cadherin蛋白表达与大肠癌浸润转移的关系

目的　探讨CD44v6和E cadherin(E cad)蛋白表达与大肠癌浸润转移的关系及相关性。方法　应用催化信号放大系统免疫组织化学技术 ,检测 90例大肠癌组织中CD44v6和E cadherin蛋白表达。结果　 90例大肠癌CD44v6和E cadherin蛋白阳性表达率分别为 75 .6%和 46.7%。CD44v6高表达及E cad低表达与大肠癌Dukes分期、浆膜浸润、淋巴结转移、肝脏转移均呈正相关 (P <0 .0 5 )。大肠癌中CD44v6表达与E cad表达呈负相关 (r =-0 .43 ,P <0 .0 0 5 )。结论　CD44v6和E cad表达具有负调节的协同作用。CD44v6和E cad表达与大肠癌浸润转移密切相关。检测CD44v6和E cad蛋白表达可作为判断大肠癌预后的客观指标。     

215例早期胃癌淋巴结转移的危险因素分析

  目的   探讨早期胃癌淋巴结转移的危险因素。   方法   回顾性分析2005年1月至2010年12月安徽医科大学附属省立医院普外科收治的215例早期胃癌患者的临床病理资料, 并研究早期胃癌淋巴结转移与临床病理因素的关系。   结果   215例患者中淋巴结转移者36例, 单因素分析显示: 肿瘤最大直径(P=0.022)、浸润深度(P=0.003)、Hp感染情况(P=0.004)均与早期胃癌淋巴结转移有关。Logistic多因素回归分析显示: 肿瘤的浸润深度与早期胃癌淋巴结转移有关(P=0.002)。   结论   肿瘤的浸润深度是影响早期胃癌淋巴结转移的独立危险因素。      

早期胃癌的淋巴结转移规律及预后分析

目的 分析早期胃癌的临床病理特征与预后之间的关系及早期胃癌的淋巴结转移规律.方法 对1994年1月～2005年10月手术治疗并有完整资料的255例早期胃癌的临床病理学资料进行回顾性分析.结果 255例患者的总5年生存率为91.4%.单因素分析显示,肿瘤浸润深度、脉管瘤栓和区域淋巴结转移与患者术后生存率有关;而性别、年龄...     

Identification of lymph node metastasis by computed tomography in early gastric cancer

ObjectiveLymph node status is critical when selecting treatment methods for patients with early gastric cancer (EGC). The aim of this study was to assess the diagnostic value of computed tomography (CT) for detection of lymph node metastasis (LNM) in patients with EGC.MethodsWe retrospectively analyzed patients who had pathologically confirmed EGC between November 2010 and January 2019. After 1:1 propensity score matching, 65 patients with LNM and 65 patients without LNM were retained for comparison. The long diameter (LD) and short diameter (SD) of all visualized lymph nodes in all stations were recorded. The diagnostic value of LNM was assessed with receiver operating characteristic analysis.ResultsAmong 130 patients, we found a total of 558 lymph nodes on the CT images. Among the diagnostic indicators, the number, sum of LD and sum of SD of lymph nodes greater than 3 mm had better discrimination. The areas under the curve were all greater than 0.75. As for different regions, the optimal cutoff values of number, the sum of LD and sum of SD were determined as follows: overall, ≥4, 19.9 mm and 13.5 mm; left gastric artery basin, ≥3, 15.7 mm and 8.6 mm; right gastroepiploic artery basin, ≥2, 8.6 mm and 7.0 mm.ConclusionsCT is valuable for diagnosing LNM in EGC patients. The number, sum of LD and sum of SD of lymph nodes greater than 3 mm are preferable indicators. Different regional lymph nodes have different optimal criteria for predicting LNM in ECG patients.     

Recurrence in early gastric cancer with lymph node metastasis

Background  Early gastric cancer (EGC) has an excellent prognosis, but some patients with lymph node-positive disease will develop recurrence. In this study we investigated the risk factors for recurrence in this selected group of patients. Methods  The clinical and pathological records of 2368 patients who underwent gastrectomy for solitary EGC between 1980 and 1999 at the National Cancer Center Hospital, Tokyo, were examined. Two hundred and thirty-eight patients (10%) were lymph node-positive (positive for lymph node metastasis) and form the population of this study. Results  Nineteen (8%) of the 238 patients with lymph nodepositive disease developed recurrence. The most common site of recurrence was lymph node (37%), followed by liver (21%). The interval between surgery and the detection of recurrence ranged from 3 to 98 months, with a median of 26 months. Multivariate analysis demonstrated that the number of metastatic nodes was an independent risk factor for recurrence. Patients with seven or more metastatic nodes had the highest rate of recurrence, at 38%. Conclusion  The number of nodes positive for metastasis was the only independent risk factor for recurrence after curative surgery in patients with lymph node-positive early gastric cancer. These high-risk patients may obtain additional survival benefit if targeted with adjuvant chemotherapy.     

Using nomogram,decision tree,and deep learning models to predict lymph node metastasis in patients with early gastric cancer: a multi-cohort study

The accurate assessment of lymph node metastasis (LNM) in patients with early gastric cancer is critical to the selection of the most appropriate surgical treatment. This study aims to develop an optimal LNM prediction model using different methods, including nomogram, Decision Tree, Naive Bayes, and deep learning methods. In this study, we included two independent datasets: the gastrectomy set (n=3158) and the endoscopic submucosal dissection (ESD) set (n=323). The nomogram, Decision Tree, Naive Bayes, and fully convolutional neural networks (FCNN) models were established based on logistic regression analysis of the development set. The predictive power of the LNM prediction models was revealed by time-dependent receiver operating characteristic (ROC) curves and calibration plots. We then used the ESD set as an external cohort to evaluate the models’ performance. In the gastrectomy set, multivariate analysis showed that gender (P=0.008), year when diagnosed (2006-2010 year, P=0.265; 2011-2015 year, P=0.001; and 2016-2020 year, P<0.001, respectively), tumor size (2-4 cm, P=0.001; and ≥4 cm, P<0.001, respectively), tumor grade (poorly-moderately, P=0.016; moderately, P<0.001; well-moderately, P<0.001; and well, P<0.001, respectively), vascular invasion (P<0.001), and pT stage (P<0.001) were independent risk factors for LNM in early gastric cancer. The area under the curve (AUC) for the validation set using the nomogram, Decision Tree, Naive Bayes, and FCNN models were 0.78, 0.76, 0.77, and 0.79, respectively. In conclusion, our multi-cohort study systematically investigated different LNM prediction methods for patients with early gastric cancer. These models were validated and shown to be reliable with AUC>0.76 for all. Specifically, the FCNN model showed the most accurate prediction of LNM risks in early gastric cancer patients with AUC=0.79. Based on the FCNN model, patients with LNM rates of >4.77% are strong candidates for gastrectomy rather than ESD surgery.     

Prognostic role of lymph node metastasis in early gastric cancer

Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.     

多基因蛋白联合检测在胃癌转移淋巴结中的表达及其相关性

目的研究多基因蛋白在胃癌及其转移淋巴结中的表达水平，探讨其在胃癌转移淋巴结中的临床意义。方法应用免疫组化法检测36例胃癌转移淋巴结中PCNA、C-erbB-2、bcl-2和p16的基因蛋白表达。结果PCNA、c—erbB—2和bcl-2在胃窦部癌转移淋巴结中N1站表达率高于N2、N3站；在各类型胃癌转移淋巴结中N2、N3站表达率呈降低趋势，p16在N3站表达率呈上升趋势；黏液腺癌转移淋巴结中p16表达率最低；分站淋巴结基因表达与原发灶的距离有关。结论联合基因蛋白检测胃癌转移淋巴结可以作为判断术后转移状况和预后的重要参考指标。     

Significance of proliferating cell nuclear antigen (PCNA) expression in gastric cancer in relation to lymph node metastasis

Proliferating cell nuclear antigen (PCNA) in gastric cancer was evaluated in relation to lymph node metastasis. A total of 125 gastric cancer patients who underwent gastrectomy were studied immunohistochemically. The PCNA-positive rate of the primary lesion with lymph node metastasis (47.6%) was significantly higher than that in those without metastasis (24.3%, P < 0.0001). The PCNA-positive rate of early gastric cancer was significantly higher in lesions with lymph node metastasis (36.9%) than in lesions without lymph node metastasis (14.7%). However, there was no significant difference between lesions with and without lymph node metastasis in advanced gastric cancer. In addition, the PCNA-positive rate in metastatic lesions (44.6%) was significantly higher than that in the primary lesion (40.0%, P = 0.001). It is concluded that gastric cancer with higher tumor growth activity has a higher rate of lymph node metastasis. Cancer cells in the metastatic foci of lymph node have a higher proliferating activity than that in the primary lesion. © 1996 Wiley-Liss, Inc.     

Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer

Background Correlations between the malignant potential and prognosis of cancer and abnormal control mechanisms of apoptosis have been discovered in a variety of cancers. Survivin is a member of the inhibiting apoptosis protein family that is abundant in embryonic and carcinoma tissues. We measured the expression of survivin mRNA in gastric cancer to determine whether levels of survivin mRNA expression could serve as an index of malignancy.Methods Expression of survivin mRNA was measured in samples of both gastric cancer and noncancerous tissue from 107 patients. Survivin mRNA was detected by the real-time polymerase chain reaction (PCR) method, and then the relationship between the survivin mRNA level and histological diagnosis was analyzed.Results Expression of survivin mRNA was observed in 105 of 107 cancerous tissues and in 101 of 107 noncancerous tissues. The Mean value of survivin mRNA expression in cancerous tissue was 5.18 ± 1.30, significantly higher (P 0.01) than that in noncancerous tissue, at 4.21 ± 1.48. No significant differences were found in the values of survivin mRNA expression according to histological classification or according to increasing depth of tumor invasion. However, survivin mRNA expression was significantly higher (P 0.01) in patients displaying lymph node metastasis (5.48 ± 1.01) than in patients without the metastasis (4.70 ± 1.55).Conclusions These results indicate that increased survivin mRNA expression begins in the early stages of gastric carcinogenesis. Moreover, the level of survivin mRNA expression may indicate the potential for lymph node metastasis in patients with gastric cancer.     

早期胃癌淋巴管密度预测淋巴结转移的研究

目的:检测淋巴管内皮标志物D2-40计算早期胃癌淋巴管密度(LVD),探讨LVD与早期胃癌有无淋巴结转移之间的关系.方法:用免疫组化SP染色法,对80例早期胃癌淋巴结未发生转移与20例早期胃癌淋巴结发生转移的癌周检测D2-40标记阳性LVD的表达水平,并进行统计学分析.结果:D2-40标记阳性LVD在早期胃癌伴有淋巴结转移癌周高于早期胃癌不伴有淋巴结转移癌周(P＜0.05),光镜下LVD的截断(cut-off)值为18.50个.结论:早期胃癌伴有淋巴结转移癌周的LVD高于早期胃癌不伴有淋巴结转移癌周,D2-40阳性LVD可用来判断有无淋巴结转移.