scholarly journals Somatic Mutations and Deletions of the E-Cadherin Gene Predict Poor Survival of Patients With Gastric Cancer

2013 ◽  
Vol 31 (7) ◽  
pp. 868-875 ◽  
Author(s):  
Giovanni Corso ◽  
Joana Carvalho ◽  
Daniele Marrelli ◽  
Carla Vindigni ◽  
Beatriz Carvalho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Survival Data ◽  
Survival Rates ◽  
Promoter Hypermethylation ◽  
Primary Tumors ◽  
Somatic Alterations ◽  
Patient Prognosis ◽  
Histologic Types ◽  
The Impact ◽  
E Cadherin

Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n = 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.

scholarly journals Impact of Palliative Gastrectomy in Patients with Incurable Gastric Cancer

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 198
Author(s):  
Ji Yeon Park ◽  
Byunghyuk Yu ◽  
Ki Bum Park ◽  
Oh Kyoung Kwon ◽  
Seung Soo Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Resection ◽  
Palliative Resection ◽  
Primary Tumors ◽  
Palliative Intent ◽  
Palliative Gastrectomy ◽  
Gastric Cancer Patients ◽  
The Impact

Background and Objectives: The prognosis of metastatic or unresectable gastric cancer is dismal, and the benefits of the palliative resection of primary tumors with noncurative intent remain controversial. This study aimed to evaluate the impact of palliative gastrectomy (PG) on overall survival in gastric cancer patients. Materials and Methods: One hundred forty-eight gastric cancer patients who underwent PG or a nonresection (NR) procedure between January 2011 and 2017 were retrospectively reviewed to select and analyze clinicopathological factors that affected prognosis. Results: Fifty-five patients underwent primary tumor resection with palliative intent, and 93 underwent NR procedures owing to the presence of metastatic or unresectable disease. The PG group was younger and more female dominant. In the PG group, R1 and R2 resection were performed in two patients (3.6%) and 53 patients (96.4%), respectively. The PG group had a significantly longer median overall survival than the NR group (28.4 vs. 7.7 months, p < 0.001). Multivariate analyses revealed that the overall survival was significantly better after palliative resection (hazard ratio (HR), 0.169; 95% confidence interval (CI), 0.088–0.324; p < 0.001) in patients with American Society of Anesthesiologists Physical Status (ASA) scores ≤1 (HR, 0.506; 95% CI, 0.291–0.878; p = 0.015) and those who received postoperative chemotherapy (HR, 0.487; 95% CI, 0.296–0.799; p = 0.004). Among the patients undergoing palliative resection, the presence of <15 positive lymph nodes was the only significant predictor of better overall survival (HR, 0.329; 95% CI, 0.121–0.895; p = 0.030). Conclusions: PG might lead to the prolonged survival of certain patients with incurable gastric cancer, particularly those with less-extensive lymph-node metastasis.

scholarly journals Pathologic Complete Response Following Neoadjuvant Therapy for Gastric Adenocarcinoma: A National Cancer Database Analysis on Incidence, Predictors, and Outcomes

2020 ◽  
pp. 000313482097208
Author(s):  
Christof Kaltenmeier ◽  
Alison Althans ◽  
Maria Mascara ◽  
Ibrahim Nassour ◽  
Sidrah Khan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Therapy ◽  
Gastric Adenocarcinoma ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Tumor Grade ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database ◽  
The Impact

Introduction With advances in multimodal therapy, survival rates in gastric cancer have significantly improved over the last two decades. Neoadjuvant therapy increases the likelihood of achieving negative margins and may even lead to pathologic complete response (pCR). However, the impact of pCR on survival in gastric cancer has been poorly described. We analyzed the rate and predictors of pCR in patients receiving neoadjuvant therapy as well as impact of pCR on survival. Methods We conducted a National Cancer Database (NCDB) analysis (2004-2016) of patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by surgical resection. Results The pCR rate was 2.2%. Following adjustment, only neoadjuvant chemoradiation, non-signet histology, and tumor grade remained as significant factors predicting pCR. pCR was a statistically significant predictor of survival. Conclusion In this NCDB study, pCR was a predictor of survival. Though chemoradiation rather than chemotherapy alone was a predictor of pCR, it was not a predictor of survival. Further studies are needed to elucidate the role of radiation in the neoadjuvant setting and to discern the impact of pCR on survival.

Prognostic Analysis of E-Cadherin Gene Promoter Hypermethylation in Patients with Surgically Resected, Node-Positive, Diffuse Gastric Cancer

2004 ◽  
Vol 10 (8) ◽  
pp. 2784-2789 ◽  
Author(s):  
Francesco Graziano ◽  
Federica Arduini ◽  
Annamaria Ruzzo ◽  
Italo Bearzi ◽  
Bostjan Humar ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gene Promoter ◽  
Promoter Hypermethylation ◽  
Diffuse Gastric Cancer ◽  
Node Positive ◽  
Prognostic Analysis ◽  
Resected Node ◽  
E Cadherin

The Impact of Herbivores on Regeneration in Four Trees From Arid Australia.

1995 ◽  
Vol 17 (2) ◽  
pp. 213 ◽  
Author(s):  
TD Auld
Keyword(s):  
Survival Data ◽  
National Park ◽  
Survival Rates ◽  
Ground Level ◽  
High Survival ◽  
Grazing Land ◽  
The Impact ◽  
Acacia Ligulata ◽  
Semi Arid ◽  
Survival Of Seedlings

The size distributions of populations of four semi-arid perennial trees were investigated within Kinchega National Park in western NSW. For Acacia ligulata, A, loderi and Alectryon oleifolius, it appears that regeneration has been eliminated or at best severely limited at most sites. Some regeneration has occurred through recruitment of vegetative suckers in Casuarina pauper. Currently these vegetative recruits have high survival rates under both rabbit and kangaroo grazing, although such grazing frequently reduces the height of vegetative suckers back to ground level. Survival of seedlings of Acacia ligulata was very limited, with highest survival when mammals were excluded. There was no survival of seedlings of Casuarina pauper in the presence of rabbits and survival was poor when rabbits were excluded. Many seedlings of both species die through desiccation. The survival data from seedlings and vegetative suckers reinforce the patterns observed in the size distribution of populations. Within Kinchega National Park, control of rabbits is essential to initiate regeneration. A reduction in the total grazing pressure (especially rabbits, sheep, cattle and goats) is necessary in critical dry periods on semi-arid and arid grazing land if regeneration of perennials is to be encouraged.

Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer

2018 ◽  
Vol 36 (2) ◽  
pp. 137-143 ◽  
Author(s):  
Hiroaki Saito ◽  
Yusuke Kono ◽  
Yuki Murakami ◽  
Yuji Shishido ◽  
Hirohiko Kuroda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Elderly Patients ◽  
Lymphocyte Count ◽  
Operating Characteristic ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Venous Invasion ◽  
Prognostic Indicator ◽  
Characteristic Analysis ◽  
Patient Prognosis

Background: Although preoperative lymphopenia is reportedly a prognostic factor in cancer patients, the association between postoperative lymphopenia and patient prognosis has not been widely studied. Methods: We enrolled 352 patients who underwent surgery for gastric cancer (GC) between January 2005 and April 2013 to analyze correlations among pre- and postoperative lymphocyte counts (LCs) and prognosis in GC patients. Results: Pre- and postoperative (obtained 1 day after surgery) LCs were significantly correlated (r = 0.496, p < 0.0001). Pre- and postoperative LCs of elderly patients were significantly lower than those of non-elderly patients. Postoperative lymphocyte count was significantly lower in patients with a differentiated tumor than in those with an undifferentiated tumor. Based on the results of receiver operating characteristic analysis, patients were classified into subgroups as: preoperative LC ≥1,676 (pre-LCHigh), preoperative LC <1,676 (pre-LCLow); and as postoperative LC ≥855 (post-LCHigh), and postoperative LC <855 (post-LCLow). Five-year overall survival rates significantly differed between pre-LCHigh (82.5%) and pre-LCLow (71.6%) groups (p = 0.023); and also between the post-LCHigh (81.5%) and post-LCLow (69.5%) groups (p = 0.0072). The 5-year disease specific survival rates were 91.3 and 82.4% in patients with post-LCHigh and those with post-LCLow, respectively, and differences were statistically significant (p = 0.015). Multivariate analysis indicated that postoperative lymphocyte count was an independent prognostic indicator, along with age, gender, tumor size, lymph node metastasis, and venous invasion. Conclusions: Postoperative lymphocyte count is a useful predictive factor for prognosis in GC patients.

Association of gene expressions of TOP2A, GGH, and PECAM1 with hematogenous, lymph-node, and peritoneal recurrence in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4019-4019
Author(s):  
Masanori Terashima ◽  
Wataru Ichikawa ◽  
Atsushi Ochiai ◽  
Koji Kitada ◽  
Issei Kurahashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Lymph Node ◽  
Peritoneal Recurrence ◽  
Stage Ii ◽  
Taqman Assay ◽  
Primary Tumors ◽  
Expression Levels ◽  
Biomarker Analysis ◽  
The Impact

4019 Background: Exploratory biomarker analysis was conducted to identify factors related to relapse sites in the ACTS-GC study, a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients (pts) with stage II/III gastric cancer. Methods: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 pts (78.3%), and 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were analyzed by quantitative RT-PCR after TaqMan assay-based pre-amplification. Gene expression levels were normalized to the geometric mean expressions of GAPDH, ACTB, and RPLP0, used as reference genes. The expression of each gene was categorized as lower or higher than the median value. The impact of gene expression on relapse site was analyzed using the 5-year relapse-free survival (RFS) data of the ACTS-GC. Results: Among the 829 pts, hematogenous, lymph-node, and peritoneal recurrence developed in 72, 105, and 138 pts, respectively. The hazard ratios (HR) (S-1 vs. surgery alone) were 0.79 (95%CI, 0.54-1.16) for hematogenous, 0.51 (95%CI, 0.31-0.82) for lymph-node, and 0.60 (95%CI, 0.42-0.84) for peritoneal recurrence. Among 63 screened genes, topoisomerase II alpha (TOP2A), gamma-glutamyl hydrolase (GGH), and platelet/endothelial cell adhesion molecule 1 (PECAM1) most strongly correlated with hematogenous, lymph-node, and peritoneal recurrence, respectively. Hematogenous RFS was significantly worse in TOP2A high pts than in low pts (HR, 2.35; 95% CI, 1.55-3.57). Lymph-node RFS was significantly worse in GGH high pts than in low pts (HR, 1.87; 95% CI, 1.13-3.08). Likewise, peritoneal RFS was significantly worse in PECAM1high pts than in low pts (HR, 2.37: 95% CI, 1.65-3.41). These factors were independent and stronger risk factors than tumor histological type on multivariate analysis. Conclusions: Expression levels of the TOP2A, GGH, and PECAM1 genes in primary tumors are respectively linked to high risks of hematogenous, lymph-node, and peritoneal recurrence in pts with stage II/III gastric cancer.

scholarly journals Evaluation of Androgen Receptor in Relation to Estrogen Receptor (AR/ER) and Progesterone Receptor (AR/PgR): A New Must in Breast Cancer?

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Giuseppe Bronte ◽  
Andrea Rocca ◽  
Sara Ravaioli ◽  
Emanuela Scarpi ◽  
Massimiliano Bonafè ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Survival Data ◽  
Epithelial Mesenchymal Transition ◽  
Case Series ◽  
Transition Process ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Early Primary ◽  
Patient Prognosis

Steroid nuclear receptors are known to be involved in the regulation of epithelial-mesenchymal transition process with important roles in invasion and metastasis initiation. Androgen receptor (AR) has been extensively studied, but its role in relation to breast cancer patient prognosis remains to be clarified. AR/ER ratio has been reported to be an unfavorable prognostic marker in early primary breast cancer, but its role in the patients with advanced disease has to be cleared. We retrospectively analyzed ER, PgR, and AR expression on a case series of 159 specimens of primary BC samples by using immunohistochemistry and 89 patients of these had luminal tumors for which AR and ER expression and survival data were available. For twenty-four patients both primary and metastatic tumors were available. A significantly shorter overall survival was observed in primary tumors with AR/PgR ratio ≥ 1.54 (HR = 2.27; 95% CI 1.30-3.97; p = 0.004). Similarly OS was significantly shorter when ER/PgR ratio ≥2 in primary tumors (HR = 1.89; 95% CI 1.10-3.24; p = 0.021). The analysis of the 24 patients who had biomarker determinations both in primary tumors and metastasis showed a better OS when AR/ER ratio in the metastasis was ≥ 0.90 (p = 0.022). Patients with a high AR/ER ratio in primary tumor that remained high in the metastasis had better prognosis in terms of OS (p = 0.011). Despite we suggested that the ratios AR/ER and AR/PgR could be used to identify patients with different prognosis, their real value needs to be better clarified in different BC settings through prospective studies.

Overview on new progress of hereditary diffuse gastric cancer with CDH1 variants

2020 ◽  
Vol 106 (5) ◽  
pp. 346-355
Author(s):  
Mu-Ni Hu ◽  
Shu-Hui Hu ◽  
Xing-Wei Zhang ◽  
Shu-Min Xiong ◽  
Huan Deng
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Promoter Hypermethylation ◽  
Hereditary Diffuse Gastric Cancer ◽  
Diffuse Gastric Cancer ◽  
Gene Therapies ◽  
Recommended Treatment ◽  
Prophylactic Gastrectomy ◽  
E Cadherin

Hereditary diffuse gastric cancer (HDGC), comprising 1%–3% of gastric malignances, has been associated with CDH1 variants. Accumulating evidence has demonstrated more than 100 germline CDH1 variant types. E-cadherin encoded by the CDH1 gene serves as a tumor suppressor protein. CDH1 promoter hypermethylation and other molecular mechanisms resulting in E-cadherin dysfunction are involved in the tumorigenesis of HDGC. Histopathology exhibits characteristic signet ring cells, and immunohistochemical staining may show negativity for E-cadherin and other signaling proteins. Early HDGC is difficult to detect by endoscopy due to the development of lesions beneath the mucosa. Prophylactic gastrectomy is the most recommended treatment for pathogenic CDH1 variant carriers. Recent studies have promoted the progression of promising molecular-targeted therapies and management strategies. This review summarizes recent advances in CDH1 variant types, tumorigenesis mechanisms, diagnosis, and therapy, as well as clinical implications for future gene therapies.

scholarly journals Association of CDH1 -160 C → A and -347 G→ GA polymorphisms and expression of E-cadherin and gastric cancer: A case-control study

2021 ◽  
Vol 37 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Adem Akçakaya ◽  
Nurcan Ünver ◽  
Tuğba Aydoğan Kiriş ◽  
Mehmet Güzel ◽  
Fatma Betül Akçakaya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Case Control Study ◽  
Demographic Data ◽  
Survival Rates ◽  
Case Control ◽  
Loss Of Function ◽  
Group A ◽  
Gastric Cancer Patients ◽  
Control Study ◽  
E Cadherin

Objective: The loss of function of the E-cadherin (CDH1) gene with -160 C→A and -347 G→GA polymorphisms is regarded as a critical step for gastric cancer. It was aimed to investigate possible association of these polymorphisms and immunoexpression of E-cadherin with gastric cancer. Material and Methods: Gastric adenocarcinoma patients and individuals with benign gastric pathologies were included in this case-control study. Demographic data and pathological findings were recorded. Immunohistochemical staining of E-cadherin expression and analysis of -160 C→A and -347 G→GA polymorphisms were done. Differences between allele frequencies of -160 C→A and -347 G→GA polymorphisms and expression of E-cadherin were the primary outcomes. Results: There were 78 gastric cancer patients (Group A) and 113 individuals with benign gastric pathologies (Group B). The number of male patients and mean age were higher in Group A (p< 0.001). -160 C→A and 347 G→GA polymorphisms and their allelic distributions showed no difference between the groups (p> 0.05 for all). There was a significant association between -160 C→A polymorphism and grade of E-cadherin expression (p= 0.013). There were no significant differences between survival rates with -160 C→A, 347 G→GA and intensity of E-cadherin expression (p> 0.05 for all). There was no significant association between -160 C→A and -347 G→GA polymorphisms and gastric cancer. Conclusion: There was no impact of E-cadherin expression on tumoral features and survival in gastric cancer. -160 C→A polymorphism may influence the expression of E-cadherin in gastric cancer.

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