Prognostic Factor For Gastric Cancer Patients Research Articles

659P - The Log Odds of Positive Lymph Nodes is an Independent Prognostic Factor for Gastric Cancer Recurrence and Mortality After Curative Resection

ABSTRACT Aim: To evaluate the prognostic value of the log odds of positive lymph nodes (LODDS) system and lymph node ratio (LNR) compared with pathological nodal (pN; 7th edition UICC/ AJCC) stage in gastric cancer (GC) patients after curative resection. Methods: A total of 513 GC patients who underwent radical gastrectomy (R0) from Jan 2005 to Dec 2013 were analyzed. LNR was defined as the ratio of metastatic lymph nodes (LN) to total LN. LODDS was calculated as log[(pnod + 0.5)/ (tnod-pnod + 0.5)], where the pnod is the number of positive LN and tnod is the total number of LN retrieved. The primary endpoint of the study was overall survival. The patients were classified into four LNR (LNR0: 0; LNR1: > 0 to 0.2; LNR2: > 0.2 to 0.5 and LNR3: > 0.50 to 1.00) and four LODDS (LODDS1: -2 to ≤ -1, LODDS2: -1 to ≤ 0, LODDS3: 0 to ≤ +1 and LODDS4: +1 to ≤ +2) groups by the best cut-off approach. Kaplan-Meier analysis with log-rank test and Cox regression model were performed. Results: The median numbers of involved and dissected LN were 5 (0-50), and and 21 (2-91), respectively. The median follow-up period was 36.7 months. In multivariate analysis, LODDS system was independent prognostic factor for GC mortality (HR:2.02, 95%CI 1.61-2.54; p 0.05). LODDS system also significantly discriminated the prognostic groups both in the patients with D1 and D2 lymphadenectomy, as well as in patients who received adjuvant chemotherapy and radiotherapy. Conclusions: LODDS system is an independent prognostic factor for GC patients. It has more potential to minimize stage migration in patients with insufficient number of LN retrieved compared to the pN and LNR classifications. Although limited practical application due to calculation procedure, LODDS system should be recommended in the countries where both D1 and D2 lymphadenectomy are performed. Moreover, it would impact the selection of patients who may benefit most from the adjuvant treatments. Disclosure: All authors have declared no conflicts of interest.

The prognostic value of CD44 expression in gastric cancer: A meta-Analysis

Several studies have been conducted to examine the association between CD44 expression and the prognosis of gastric cancer (GC). However, the conclusions remain controversial. We conducted a meta-analysis study of 16 published studies with 2403 patients to evaluate the correlation between CD44 expression and clinicopathological characteristics and overall survival of the GC patients. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the correlation of CD44 expression with the clinicopathological features of GC patients. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to assess the association between CD44 and prognosis of GC patients. Total CD44 expression was detected in ten studies, and CD44v5 and CD44v6 expressions were detected in one and five papers, respectively. The results revealed that CD44 expression was associated with some clinicopahological features, such as lymph node metastasis (pooled OR=1.81, 95% CI=1.44–2.34, P=0.000), distant metastasis (pooled OR=3.29, 95% CI=1.90–5.67, P=0.001) and TNM stage (Pooled OR=1.84, 95% CI=1.13–2.99, P=0.014). Moreover, we also found that GC patients with positive CD44 expression had a worse prognosis than the ones with negative CD44 expression (HR=1.93, 95% CI=1.54–2.42, P=0.000). In stratified analysis, the combined HR with CD44 and CD44v6 was 2.20 (95% CI=1.81–2.67) and 1.70 (95% CI=1.00–2.90), respectively. These results suggested that positive CD44 expression could predict a lower overall survival rate and could be an independent dangerous prognostic factor in GC patients.

Thrombocytosis is a significant indictor of hypercoagulability, prognosis and recurrence in gastric cancer.

Although thrombocytosis has been reported in a variety of cancer types, the standard of thrombocytosis in gastric cancer (GC) and the association between thrombocytosis and the clinicopathological features of patients with GC remain unclear. In the present study, 1,763 GC patients were retrospectively filtered by preoperative thrombocytosis and compared with control group A (n=107) that had benign gastric lesions and control group B (n=100) that were GC patients with a normal platelet (PLT) count. Associations between clinical variables and preoperative PLT counts were assessed by univariate and multivariate analyses. Kaplan-Meier survival curves and Cox regression were used to evaluate the effect of thrombocytosis on prognosis. Sensitivities and specificities of the PLT counts in predicting recurrence were analyzed via area under the receiver operating characteristic curve (AUROC). The results indicated that the incidence of thrombocytosis in GC patients was higher than in benign gastric lesion patients, with 4.03% of GC patients having a PLT count >400×109/l (P=0.014) and 12.08% had a PLT count >300×109/l (P<0.001). For the patients with a PLT count >400×109/l, the frequency of abnormal PLT counts in GC correlated with tumor size (P<0.001), tumor, node and metastasis (TNM) classification (P=0.002), invasive degree (P=0.003) and D-dimer (P=0.013) and fibrinogen concentrations (P=0.042). Tumor size (P=0.002), TNM classification (P<0.001) and depth of penetration (P=0.001) were independent factors for thrombocytosis. However, thrombocytosis functioned as an independent prognostic factor for GC patients with a PLT count >400×109/l (relative risk, 1.538; 95% confidence interval, 1.041–2.271). In the majority of patients (17/24) with a high preoperative PLT count that decreased to a normal level following resection, PLT levels increased again at recurrence. Sensitivities and specificities of thrombocytosis for recurrence in those patients were 70.8 and 83.3%, respectively (AUROC, 0.847; P=0.01). Therefore, a PLT count of 400×109/l is a suitable threshold for defining thrombocytosis in GC. Thrombocytosis was shown to affect the blood hypercoagulable state and also have a negative prognostic value for GC patients. PLT monitoring following surgery was useful to predict the recurrence for specific GC patients that suffered preoperative thrombocytosis but had restored PLT levels following resection.

Overexpression of PrPc, combined with MGr1‐Ag/37LRP, is predictive of poor prognosis in gastric cancer

Prion protein (PrPc) has been previously reported to be involved in gastric cancer (GC) development and progression. However, the association between expression of PrPc and GC prognosis is yet poorly characterized. In the present study, the expressions of PrPc and MGr1-Ag/37LRP, a protein interacting with PrPc, were detected using the tissue microarray technique and immunohistochemical method to compare clinicopathological parameters of 238 GC patients. We found that the expressions of PrPc and MGr1-Ag/37LRP were upregulated in GC lesions compared with their expressions in adjacent noncancerous tissues (p < 0.01). High expression of PrPc was detected in 37.39% (89/238) of GC patients and positively correlated with the expression of MGr1-Ag/37LRP (r = 0.532, p < 0.001). PrPc expression was associated with a number of clinicopathological parameters including depth of invasion and lymph node metastasis of the tumor (p < 0.001). High expression of PrPc brought a poorer prognosis than low PrPc expression. Moreover, GC patients with high level of PrPc and high level of MGr1-Ag/37LRP had the poorest prognosis. Multivariate survival analysis suggested that, along with other parameters, combined expression of PrPc and MGr1-Ag/37LRP was independent prognostic factors for GC patients. These data indicates that overexpression of PrPc, combined with MGr1-Ag/37LRP, is predictive of poor prognosis in GC and thereby could be used to guide the clinical decision.What's new?Prion protein was originally exclusively associated with prion disease but has now been linked to other processes such as cancer and inflammation. Here the authors examined the role of prion protein and its receptor MGr1-Ag/37LRP in gastric cancer. They found that both factors were upregulated in gastric cancer, and not in neighboring healthy, tissues and established the combined expression of prion protein and MGr1-Ag/37LRP as an independent prognostic factor for gastric cancer patients. These studies support a new role of prion protein in cancer and identify a new biomarker for a more accurate prediction of prognosis in gastric cancer patients.

Overexpression of FOXC1 correlates with poor prognosis in gastric cancer patients

The aim of this study was to determine FOXC1 expression in gastric tissues, and the clinical significance of FOXC1 in the development, progression and metastasis of gastric cancer (GC). We screened GCs for the expression of FOXC1 using the Affymetrix U133 plus 2.0 Gene Chip Array, and found that expression was significantly higher in GC tissues than in controls. Furthermore, we validated the expression levels of FOXC1 using real-time quantitative RT-PCR (qRT-PCR), and of FOXC1 using immunohistochemistry (IHC). Our study showed that expression levels of FOXC1 mRNA and FOXC1 in GC tissues were significantly higher than those in corresponding non-tumour tissues. High FOXC1 expression correlated with the degree of histological differentiation (P<0.01), TNM stage (P<0.001), invasive depth (P<0.05), lymph node metastasis (P<0.05), and distant metastasis (P<0.01). Survival analysis revealed that patients with high FOXC1 expression had shorter overall survival than those with low expression (P<0.001). Multivariate analysis showed that high FOXC1 expression was an independent prognostic factor for GC patients (P<0.01). Overexpression of FOXC1 may play a key role in the progression of GC, and FOXC1 expression may serve as a useful marker for predicting the outcome of patients with GC.

Prognostic value of surgical margin status in gastric cancer patients

It has been reported that positive surgical margin is one of the most significant risk factors for local recurrence and poor survival. However, the survival of gastric cancer (GC) patients with positive margin is still controversial. A total of 1025 stage I-III GC patients who underwent gastrectomy with curative intent between January 2003 and April 2008 in our centre were enrolled in this study, of whom, 75 patients got a microscopic positive resection margin. Other 950 patients with negative resection margin were used for comparison. Borrmann type and extranodal metastasis were independent risk factors for positive margin. The 5-year overall survival for the patients with positive margin is merely 13.3%. Survival in such patients was similar to that of the patients staged IIIc with R0 resection. In multivariate analysis, surgical margin status was found to be an independent prognostic factor for GC patients, while histology, tumour location, TNM stage and chemotherapy were independently associated with overall survival for patients with positive margin. Surgical margin status is an independent prognostic factor for GC. Patients with positive margin have a poor prognosis, similar to that of IIIc stage disease. When the tumour demonstrates infiltrative growth pattern (Borrmann type III and IV) and the surgical margin status is difficult to determine, extended gastrectomy should be implemented to ensure an R0 resection. Those high-risk patients should be considered for postoperative chemotherapy.

Increased expression of α5β1-integrin is a prognostic marker for patients with gastric cancer

The study was to evaluate the association of expression level of α5β1-integrin with clinicopathologic features and prognosis in gastric cancer (GC). The expression of α5β1-integrin in normal gastric mucosa and GC tissue was detected with immunohistochemistry. The level of α5 and β1 mRNA in GC tissues and non-neoplastic tissues was evaluated in 48 paired cases by quantitative real-time polymerase chain reaction (qRT-PCR). Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. The α5β1-integrin expression was detected in 68.3 % (127/186) GC samples, and there was a significant difference on their positive expression rate between GC tissue and normal gastric mucosa (P < 0.001). The positive expression rate of α5β1-integrin in patients with poor histologic differentiation (P = 0.001), lymph node metastasis (P < 0.001), and recurrence (P < 0.001) group was heightened. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expresser of α5β1-integrin revealed a highly significant difference in human GC tissue (P = 0.002), which suggested that overexpression of α5β1-integrin is associated with a worse prognosis. Multivariate analyses showed that α5β1-integrin expression was independent risk factor predicting overall survival [Hazard ratio (HR) 1.594, 95 % confidence interval (CI) 1.236-2.408, P = 0.006] and disease-free survival [HR 3.952, 95 % CI 1.676-9.861, P = 0.003] in GC. The α5β1-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of GC. The current study shows that α5β1-integrin may be an independent prognostic factor for GC patients.

Double-positive expression of high-mobility group box 1 and vascular endothelial growth factor C indicates a poorer prognosis in gastric cancer patients

BackgroundAlthough many studies have indicated that high-mobility group box 1 protein (HMGB1) is associated with oncogenesis and a worse prognosis, the prognostic value of HMGB1 in gastric cancer (GC) remains unclear. In the present work, we aimed to evaluate the role of HMGB1 in GC and examined whether aberrant expression of both HMGB1 and vascular endothelial growth factor C (VEGF-C) increased the malignant potential of GC.MethodsA total of 166 GC patients and 32 normal subjects were enrolled. HMGB1 and VEGF-C expression was detected by tissue microarrays (TMAs) and immunohistochemical staining. The correlation between HMGB1 and VEGF-C expression and their relationships with clinicopathological GC variables were examined. Univariate and multivariate analyses were performed using the Cox proportional hazard model to predict the factors related to the patients‘ overall survival rates.ResultsHMGB1 and VEGF-C expression were observed in 81 (48.80%) and 88 (53.01%) tumors, respectively, significantly higher than the rates among the corresponding controls. In addition, HMGB1 and VEGF-C expression were positively correlated (R2 = 0.972). HMGB1 expression was also closely associated with tumor size, pT stage, nodal status, metastasis status, TNM stage, and poor prognosis. Multivariate survival analysis indicated that patients with HMGB1 and VEGF-C coexpression had the worst prognoses and survival rates (hazard ratio, 2.78; log rank P<0.001).ConclusionsHMGB1 is commonly expressed in GC. Combined evaluation of HMGB1 and VEGF-C may serve as a valuable independent prognostic factor for GC patients.

Abstract 1144: Expression of tropomyosin-related kinase B (TrkB) at the tumor invasive front as an independent prognostic factor in gastric cancer.

Abstract Background. Previously, we have reported the association between the expression of tropomyosin-related kinase B (TrkB) in tumor cells and gastric tumor progression, chemoresistance of esophageal cancer, and epithelial-mesenchymal transition in colorectal cancer. In gastric cancer, high tumoral TrkB mRNA level demonstrated to be an independent prognostic factor. Aim. In this study, we investigated the TrkB protein expression in tumor cells using immunohistochemistry, and evaluated its clinical and prognostic significance in patients with human gastric cancer (GC). Materials and methods. Three hundred and twenty (n=320) samples of GC patients were investigated for the TrkB protein expression in tumor cells using a standard immunohistochemistry (IHC). The IHC score of TrkB in tumor cells was determined on the basis of both staining intensity and the percentage of positive cells. The IHC score was dichotomized at the median value as a cutoff value. The association between the TrkB protein expression in tumor cells and clinicopathological features was analyzed. Impact of TrkB protein expression in tumor cells on overall survival (OS) was also analyzed using univariate and multivariate analyses. Results. Immunoreactive TrkB protein was localized in both cytoplasm and nucleus of gastric cancer cells. High cytoplasmic TrkB expression was significantly associated with larger tumor size (p &amp;lt;0.01), well differentiated histology (&amp;lt;0.01), advanced T stage (p &amp;lt;0.01), lymphovascular invasion (p &amp;lt;0.01), lymph node involvement (p &amp;lt;0.01), synchronous distant metastasis (p &amp;lt;0.01), and advanced UICC stage (p &amp;lt;0.01). Fifty patients (16%) showed a higher TrkB expression in either cytoplasm or nucleus of tumor cells at the tumor invasive front, as compared with the tumor center. In univariate analysis, higher TrkB expression at the tumor invasive front was significantly associated with poor prognosis [hazard ratio (95%): 4.50 (2.78-7.18), p&amp;lt;0.01]. High cytoplasmic TrkB expression did not reach statistical significance. In multivariate analysis, higher TrkB expression at the tumor invasive front retained an independent prognostic factor for GC patients [hazard ratio (95%): 1.77 (1.07-2.88), p=0.03]. Conclusions. Tumoral TrkB expression was associated with tumor progression in human gastric cancer. Increased TrkB at the tumor invasive front was an independent prognostic factor in patients with gastric cancer. Citation Format: Koji Tanaka, Tadanobu Shimura, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Masaki Ohi, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki. Expression of tropomyosin-related kinase B (TrkB) at the tumor invasive front as an independent prognostic factor in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1144. doi:10.1158/1538-7445.AM2013-1144

Abstract 1139: Prognostic value of angiopoietin-like protein 2 (ANGPTL2) at the tumor margins in patients with gastric cancer.

Abstract Background. Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family.It has been reported to act as a causative mediator of chronic inflammation andmetabolic abnormalities. In ovarian and lung cancer, ANGPTL2 expression in tumor cells was reported to be associated with unfavorable prognosis. So far,clinical and prognostic significance of ANGPTL2 in human gastric cancer remains unknown. Aim. This study investigated the expression of ANGPTL2 in tumor cells using immunohistochemistry and to evaluate its clinical and prognostic significance in patients with human gastric cancer (GC). Materials and methods. Two hundred and eighty two (n=282) samples of GC patients were investigated for the expression of ANGPTL2 in tumor cells using standard immunohistochemistry (IHC). The IHC score of ANGPTL2 in tumor cells was determined on the basis of both staining intensity and the percentage of positive cells. The IHC score was dichotomized at the cutoff value predictive of overall survival using a non-parametric receiver operating characteristic analysis. The association between the expression of ANGPTL2 intumor cells and clinicopathological features was analyzed. Impact of ANGPTL2 expression in tumor cells on overall survival (OS) was also analyzed usingunivariate and multivariate analyses. Results. ANGPTL2 protein was localized mainly in the cytoplasm of tumor cells, and partly in the nucleus. High cytoplasmic ANGPTL2 was significantly associated with higher age (p=0.04), larger tumor size (p &amp;lt;0.01), well differentiated histology (&amp;lt;0.01), advanced T stage (p&amp;lt;0.01), lymphovascularinvasion (p &amp;lt;0.01), lymph node involvement (p &amp;lt;0.01), synchronous liver metastasis (p&amp;lt;0.01), and advanced UICC stage (p &amp;lt;0.01). Twenty-four patients (8.5%) showed higher cytoplasmic ANGPTL2 staining at the tumor invasive margin, as compared with the tumor center. In univariate analysis, high cytoplasmic ANGPTL2 and higher cytoplasmic ANGPTL2 at the invasive margin were significantly associated with poor prognosis (p &amp;lt;0.01). In multivariate analysis, both high cytoplasmic ANGPTL2 and higher cytoplasmicANGPTL2 at the invasive margin retained an independent prognostic factor for GC patients [hazard ratio (HR)=2.67 (p=0.014) and 2.54 (p=0.015), respectively]. Conclusions. Tumoral ANGPTL2 expression was associated with gastric tumor progression. Increased ANGPTL2 at both tumor center and invasive margin were independent prognostic indicators in patients with gastric cancer. Citation Format: Tadanobu Shimura, Koji Tanaka, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Tsutomu Nobori, Masato Kusunoki. Prognostic value of angiopoietin-like protein 2 (ANGPTL2) at the tumor margins in patients with gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1139. doi:10.1158/1538-7445.AM2013-1139

Increased Myeloid-Derived Suppressor Cells in Gastric Cancer Correlate with Cancer Stage and Plasma S100A8/A9 Proinflammatory Proteins

Immune dysfunction may contribute to tumor progression in gastric cancer (GC) patients. One mechanism of immune dysfunction is the suppression of T cell activation and impairment of the efficacy of cancer immunotherapy by myeloid-derived suppressor cells (MDSCs). We assessed the phenotype and immunosuppressive function of MDSCs in GC patients. We further investigated the role of S100A8/A9 in GC and the relationship between S100A8/A9 and MDSC function. Lastly, the effect of MDSCs on survival rates and its potential as a prognostic factor in GC patients were investigated. MDSCs from PBMCs of GC patients were identified by comparing the expression of specific surface markers with PBMCs from healthy individuals. The ability of MDSCs to suppress T lymphocyte response and the effect of S100A8/A9 and RAGE blocking were tested in vitro by (autologous) MLR. GC patients had significantly more MDSCs than healthy individuals. These MDSCs suppressed both T lymphocyte proliferation and IFN-γ production and had high arginase-I expression. Levels of S100A8/A9 in plasma were higher in GC patients compared with healthy individuals, and they correlated with MDSC levels in the blood. Blocking of S100A8/A9 itself and the S100A8/A9 receptor RAGE on MDSCs from GC patients abrogated T cell effector function. We found that high levels of MDSCs correlated with more advanced cancer stage and with reduced survival (p = 0.006). S100A8/A9 has been identified as a potential target to modulate antitumor immunity by reversing MDSC-mediated immunosuppression.

Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer

Matrix metalloproteinase 2 (MMP-2) is able to degrade type IV collagen, and thus plays a key role in the migration of tumor cells. MMP-2 activity is inhibited by its tissue inhibitor (TIMP-2). The imbalance between MMPs and TIMPs may facilitate progression of cancer cells. The aim of this study was to compare the clinical importance of MMP-2 and TIMP-2 to that of classical tumor markers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in the diagnosis of gastric cancer (GC) by calculating the diagnostic criteria and estimating the levels of MMP-2, TIMP-2, CEA and CA 19-9 in GC patients in relation to clinicopathological features of cancer. We found that serum levels of MMP-2 and TIMP-2 were significantly lower, whereas serum tumor markers were higher, in GC patients than in healthy subjects. Moreover, concentrations of TIMP-2 and CEA correlated with gastric wall infiltration, while CA 19-9 levels correlated with gastric wall infiltration and the presence of nodal metastasis. None of the proteins tested was found to be an independent prognostic factor for GC patients' survival. The percentage of true positive results of TIMP-2 (61%) was higher than those of MMP-2 (54%) and the classical tumor markers CEA (21%) and CA 19-9 (31%). The highest diagnostic sensitivity was observed for the combined use of TIMP-2 with MMP-2 (77%). The results suggest the greater importance of serum MMP-2 and TIMP-2 than of the classical tumor markers CEA and CA 19-9 in the diagnosis of GC. But this issue requires further investigation.

CDH1 structural alterations as novel prognostic biomarker in gastric cancer patients.

42 Background: Loss of CDH1 function occurs in sporadic gastric cancer (GC) progression by different molecular mechanisms. Hypermethylation and somatic mutations are considered the most frequent events. About 50% of sporadic diffuse GC shows CDH1 promoter of hypermethylation and 30% harbor somatic mutations; loss of heterozygosity (LOH) is documented in only 5% of diffuse GC cases. The present study aims to asses CDH1 alterations in 246 GC and study associated clinicopathologic features and family history of GC. Methods: Bisulphite treated tumoral DNA was used for E-cad promoter methylation. A region of 221 bps was amplified using flanking primers and direct sequencing. To search for somatic mutations the hotspot region of E-cad was amplified and directly sequenced. For LOH analysis tumor and matched normal mucosae were amplified in three microsatellite markers (D16S3025, D16S496, D16S3067) flanking the CDH1 locus. Results: Promoter hypermethylation was the most frequent event occurring in 20.7% (51 of 246) of the cases. We found 26 (10.6%) cases affected by structural alterations (three with somatic mutations and 23 with LOH). Promoter CDH1 methylation is associated with the diffuse type of GC (p = 0.017) and the presence of distant lymph node metastasis (p = 0.043). We identified association between male gender and structural CDH1 alterations (p = &lt;0.001), R1/2 radicality of resection (p = 0.015). We verified a correlation between advanced stages and CDH1 promoter methylation (p = 0.033). Kaplan-Meier survival analysis estimates that CDH1 structural alterations participate as poor prognostic factor in GC patients (p = 0.017). Conclusions: Considering the reversible nature of hypermethylation phenomena, demethylating drugs have emerged as possible chemopreventive strategies in solid tumors. Moreover, we verify that epigenetic changes of E-cadherin leading to its decrease protein expression induce an invasive behaviour to neoplastic cells; as structural alterations of CDH1 gene is assess as predictive of worse prognosis we found a new molecular biomarker of prognosis in GC that can be used to predict the clinical prognosis of the patients. No significant financial relationships to disclose.