Poor Survival In Gastric Cancer Research Articles

Down-regulation of the claudin-18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype

Gastric cancer (GC) is one of the most common malignancies worldwide. Genes whose expression is down-regulated in GC may be tumour suppressor genes. In the present study, genes with decreased expression in GC were screened for by serial analysis of gene expression (SAGE) data analysis and reverse transcription (RT)-polymerase chain reaction (PCR), and CLDN18 (encoding claudin-18) was identified. Quantitative RT-PCR revealed that expression of CLDN18 was down-regulated in 13 (56.5%) of 23 GCs. Immunostaining showed that normal gastric mucosa and Paneth cells of the duodenum expressed claudin-18 on cell membranes. Expression of claudin-18 was reduced in several intestinal metaplasias of the stomach. Of 20 samples of gastric adenoma, 18 (90.0%) showed decreased claudin-18 expression. Down-regulation of claudin-18 was observed in 84 of 146 GCs (57.5%) and correlated with poor survival in 65 advanced GCs (p = 0.0346). In addition, expression of the gastric and intestinal phenotypes of GC was examined by immunostaining for MUC5AC, MUC6, MUC2, and CD10. Of 38 GCs showing only the intestinal phenotype, down-regulation of claudin-18 was observed in 28 (73.7%), whereas in the remaining 108 GC cases, down-regulation of claudin-18 was observed in 56 (51.9%) (p = 0.0224). These results indicate that claudin-18 is a good marker of poor survival in GC. Down-regulation of claudin-18 may be involved in GCs with an intestinal phenotype, and may be an early event in gastric carcinogenesis.

Lymphovascular Invasion Is Associated With Poor Survival in Gastric Cancer

To examine a population-based cohort for the association between clinicopathologic predictors of survival and immunohistochemical markers (IHC), and to assess changes in gene expression that are associated with lymphovascular invasion (LVI). LVI has been associated with poor survival and aggressive tumor behavior. The molecular changes responsible for the behavior of gastric cancer have yet to be determined. Characterization of IHC markers and gene expression profiles may identify molecular alterations governing tumor behavior. : Clinicopathologic and survival data of 114 patients were reviewed. Archival specimens were used to construct a multitumor tissue array that was subjected to IHC of selected protein targets. Correlation of IHC with tumor thickness (T status), LVI and prognosis was studied. Microarray analysis of fresh gastric cancer tissue was conducted to examine the gene expression profile with respect to LVI. In a multivariate analysis, nodal status (N), metastasis (M), and LVI were independent predictors of survival. LVI was associated with a 5-year survival of 13.9% versus 55.9% in patients in whom it was absent. LVI correlated with advancing T status (P = 0.001) and N status (P < 0.001). IHC staining of cyclooxygenase-2 (COX-2) correlated with T status, tumor grade, lymph node positivity, and IHC staining of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Microarray analyses suggested differential expression of oligophrenin-1 (OPHN1) and ribophorin-II (RPNII) with respect to LVI. LVI was an independent predictor of survival in gastric cancer. Expression of COX-2 may facilitate tumor invasion through MMP-2 and MMP-9 activation. OPHN1 and RPN II appeared to be differentially expressed in gastric cancers exhibiting LVI. The reported function of OPHN1 and RPN II makes these gene products promising candidates for future studies involving LVI in gastric cancer.

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

Gastric cancer is a common tumor worldwide and a tremendous health burden. However, the underlying mechanisms of tumorigenesis in this cancer's development are primarily undefined. Allelic imbalance (AI) of 8p has been reported in many cancers, yet, the target(s) of alteration and the importance of allelic imbalance on this chromosomal arm in gastric carcinoma development remained to be characterized. Our findings confirmed a high rate of AI on 8p in gastric cancers. Moreover, we demonstrated that AI on 8p, either overall or at marker D8S560, was associated with poorer survival in patients with gastric cancer. Finally, gastric cancers with a high rate of microsatellite instability were significantly associated with noncardia tumors and with female gender.

Reduction in membranous expression of beta-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer.

β-catenin, a component of the E-cadherin–catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of β-catenin is common in colorectal neoplasia. β-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular β-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, β-catenin and α-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, α- and β-catenins using microwave unmasking and an avidin–biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of β-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P = 0.0014), and was associated with poor differentiation (P = 0.0015) and short survival (P = 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of β-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P = 0.02). Neither E-cadherin or α-catenin expression correlated with survival. Reduced membranous expression of β-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in β-catenin expression from those found in colon cancer merit further study. © 1999 Cancer Research Campaign