The HER2 gene, which is located on chromosomes 17, is a therapeutic target for cancer. Amplification of HER2 has been described in several tumor types. However, few studies of HER2 gene amplification and protein expression in esophageal carcinoma have been conducted. This study was to investigate the relationship between the expression of HER2/neu and the clinical characteristics, including survival rate, of esophageal squamous carcinoma. The clinical data of 145 patients admitted in Renmin Hospital of Wuhan University, from 2000 to 2005, were reviewed. The HER2 protein expression and gene status in 145 esophageal carcinomas were evaluated using immunohistochemistry and fluorescence in situ hybridization. The survival rate was calculated by the Kaplan-Meier method and the log-rank test using SPSS13.0 software. Compared to normal esophageal epithelium (23/95, 24.2%), HER2 protein was overexpressed in most esophageal squamous carcinoma tissues (60/145, 41.4%), of which 45 (31.0%) were 2+ and 15 (10.4%) were 3+, HER2 overexpression associated significantly with HER2 gene amplification. There is a correlation between the overexpression of HER2 and the differentiation of the carcinoma, the HER2 gene amplification and the differentiation of the carcinoma and the tumor stage. According to univariate analysis, there was a significant difference in survival rates when cases with and without HER-2/neu overexpression or amplification were compared. HER-2/neu amplification/overexpression may be used as an independent prognostic factor in patients with esophageal squamous cancer, and patients with HER-2/neu amplification/overexpression might be potential candidates for new adjuvant therapies that involve the use of humanized monoclonal antibodies.
Although it has been shown that polymorphisms in one-carbon metabolism (OCM) pathway are associated with gastric cancer (GC), their interactions and contributions for patients’ survival are elusive. In this study, we investigated the effects of polymorphisms and their interactions on the survival of GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR 677C > T, 1298A > C), Methionine synthase reductase (MTRR 66A > G), Methionine synthase (MTR 2756A > G), and Thymidylate synthase (TS 3′-UTR ins6 > del6, 5′-UTR 2R > 3R). We recruited 919 GC patients from 1998 to 2006. The Kaplan–Meier plots, Cox regression analyses and the log-rank tests were carried out in this study. MTHFR 1298CC genotype showed protective effect (HR = 0.444, 95% CI = 0.210–0.940). MTRR 66 GA + GG genotypes decreased the risk of death (HR = 0.793, 95% CI = 0.651–0.967) in general, and in subgroups with more pronounced diffuse type, greater depth of invasion (T2/T3/T4), higher level lymph node metastasis (N1/N2/N3), advanced TNM stages (II/III level) and 5-Fu treatment. However, the improved survival disappeared when GC patients simultaneously had MTR 2756 GA + GG genotypes (HR = 1.063, 95% CI = 0.750–1.507). Although MTRR 66GA genotype was not associated with the survival of GC patients, patients with simultaneous MTRR 66GA and MTR 2756AA genotypes exhibited significant risk reduction of death (HR = 0.773, 95% CI = 0.609–0.981). MTHFR 1298 CA + CC combined with TS 5-UTR 2R3R + 3R3R genotypes (HR = 0.536, 95% CI = 0.315–0.913) also increased patient survival rates. Our results suggest that the MTRR 66A > G and MTHFR 1298A > C polymorphisms may be useful prognostic biomarkers for GC patients.
5-fluorouracil (5-FU) is widely used to treat patients with gastric cancer (GC). However, the response rate is quite heterogeneous. The single nucleotide polymorphisms (SNPs) and their interactions of genes in the one-carbon metabolism (OCM) pathway, including Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), Methionine synthase (MTR), and Thymidylate synthase (TS), significantly affect 5-FU metabolism. In this study, 650 stage II-III patients were recruited from 1998 to 2006. Among them, 251 received 5-FU treatment and other 399 patients were untreated. The Cox regression analysis, log-rank tests and Kaplan–Meier plots were adopted. In the chemotherapy cohort, MTRR 66 GA + GG genotypes decreased death risk, however, the protect effect of MTRR 66 GA + GG disappeared when GC patients simultaneously had MTHFR 677TT + TC or MTR 2756GG + GA genotypes. TS 5′-UTR 2R3R + 3R3R genotypes also prolonged overall survival of patients treated with 5-FU. And this favorable prognosis obviously enhanced when GC patients simultaneously had TS 3′-UTR DD + DI and TS 5′-UTR 2R3R + 3R3R genotypes. Our findings showed that the polymorphisms of MTRR 66 A > G and TS 5′-UTR 3R > 2R may be potential prognostic factors for GC patients receiving 5-FU.
BackgroundMyelin transcription factor 1 (MYT1) and its homologue MYT1-like (MYT1L) are the two main members of MYT/NZF family transcription factors, which are highly related, share a high degree of identity and show similar regulatory functions in neural development. There are evidences from several cytology experiments showing that MYT1 is associated with carcinoma.Methodology/Principal FindingsIn the present study, we genotyped 944 surgically resected gastric cancer patients by the SNaPshot method to explore the association of MYT1L rs17039396 polymorphism with survival of gastric cancer in a Chinese population. We found that cardia cancer patients carrying MYT1L rs17039396 GG genotype survived for a significantly shorter time than those carrying the GA genotype. This significance was enhanced in the dominant model (GG vs. GA/AA, log-rank P = 0.001), suggesting a potential protect role of the variant A allele. Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer (adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) = 0.40–0.81). Stratification analyses further showed that such protective effect was statistically significant in subgroups of patients with tumor size ≤5 cm (adjusted HR = 0.34, 95%CI = 0.19–0.64), well-moderate gastric cancer (adjusted HR = 0.59, 95%CI = 0.35–0.98), no lymph-node metastasis (adjusted HR = 0.49, 95%CI = 0.31–0.76), no distant metastasis (adjusted HR = 0.59, 95%CI = 0.41–0.84).Conclusions/SignificanceIn conclusion, these data represents the first demonstration that MYT1L rs17039396 variants could indentified as a favorable prognostic indicator for gastric cancer, particularly among the cardia gastric cancer. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.
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