Genetic Aspects of Gastric Cancer Instability

Hudler, Petra

doi:10.1100/2012/761909

Cited by 94 publications

(87 citation statements)

References 110 publications

(105 reference statements)

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“…Consistent with prior studies, loss of MLH1 and PMS2 was the predominant pattern. 40,45 The mechanism is predominantly hypermethylation of MLH1 promoter 6,46 and, less commonly, mutations in MLH1 and MSH2. 46 Notably, mismatch repair deficiency and TP53 mutations are not mutually exclusive carcinogenic pathways.…”

Section: Discussionmentioning

confidence: 99%

A protein and mRNA expression-based classification of gastric cancer

et al. 2016

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The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques. Gastric carcinoma is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. Despite better control over known risk factors and development of new chemotherapeutic and targeted agents, in the United States, the 5-year overall survival for gastric cancer patients is only 29%. 1 With regard to patient stratification, although several morphologic classifications have been developed, one broadly used system is the Lauren classification, which divides gastric adenocarcinoma into intestinal and diffuse types. 2 The simple two-tiered classification gives a general understanding of the histogenesis and biology of gastric cancer, and has been particularly helpful in evaluating the epidemiologic data. Another widely used system is the WHO classification, which is based on more precise histologic patterns. It is an all-inclusive system, which recognizes all the rare subtypes that were not identified in the Lauren classification. 3 Nevertheless, its clinical utility is doubtful as there is little difference in outcomes between the distinct histological subgroups.Following the successful Trastuzumab for Gastric Cancer (ToGA) trial, the only validated predictive biomarker for personalized therapy of gastric cancer is limited to human epidermal growth factor receptor (Her2) protein expression. 4 Recently, anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody (ramucirumab) has been FDA approved, and anti-epidermal growth factor receptor (EGFR) an...

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Section: Discussionmentioning

confidence: 99%

A protein and mRNA expression-based classification of gastric cancer

et al. 2016

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“…GC is derived by three known molecular mechanisms including chromosome instability, microsatellite instability and epigenetic alterations (Tan et al, 2012), which lead to deregulation of critical genes expression and cell signaling pathways, thoroughly (Hudler, 2012;Zabaleta, 2012). To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to determine DPPA2 protein expression in tumor tissues of GC and their related margin normal tissues to evaluate the probable associations between the protein expression and different clinicopathological variables of the patients.…”

Section: Dppa2 Protein Expression Is Associated With Gastric Cancer Mmentioning

confidence: 99%

“…The considerable geographical variations have been reported for GC distribution. While GC incidence rate in developed regions such as Norway is very low (6.9 and3.0 per 105 in males and females, respectively) (Hudler, 2012), in less developed areas, such as Eastern Asia, it is approximately 6-fold higher (42.4 and 18.3 vs. 6.9 and 3.0) (Ferlay et al, 2010).…”

Section: Introductionmentioning

confidence: 98%

DPPA2 Protein Expression is Associated with Gastric Cancer Metastasis

Shabestarian

Ghodsi²,

Mallak³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Gastric cancer (GC) as the fourth most common cause of malignancies shows high rate of morbidity appropriating the second leading cause of cancer-related death worldwide. Developmental pluripotency associated-2 (DPPA2), cancer-testis antigen (CT100), is commonly expressed only in the human germ line and pluripotent embryonic cells but it is also present in a significant subset of malignant tumors. To investigate whether or not DPPA2 expression is recalled in GC, our aim in this study was to elucidate DPPA2 protein expression in gastric cancer. Fifty five GC tumor and their related margin normal tissues were recruited to evaluate DPPA2 protein expression and its probable associations with different clinicopathological features of the patients. DPPA2 was overexpressed in GC cases compared with normal tissues (P < .005). While DPPA2 expression was detected in all GC samples, its high expression was found in 23 of 55 tumor tissues (41.8%). Interestingly, 50 of 55 normal samples (90.9%) were negative for DPPA2 protein expression and remained 5 samples showed very low expression of DPPA2. DPPA2 protein expression in GC was significantly correlated with lymph node metastasis (p = 0.012). The clinical relevance of DPPA2 in GC illustrated that high level expression of this protein was associated with lymph node metastasis supporting this hypothesis that alteration in DPPA2 was associated with aggressiveness of gastric cancer and may be an early event in progression of the disease. DPPA2 may be introduced as a new marker for invasive and metastatic GCs.

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“…It is a common topic that patients die because of metastases. The major hope is to prevent or treat in an efficient way metastatic disease [9,10].…”

Section: Limitations Of Therapeutic Resistancementioning

confidence: 99%