目的 探讨原发性涎腺黏液表皮样癌(mucoepidermoid carcinoma,MEC)中MAML2基因重排与临床病理特征的相关性.方法 采用荧光原位杂交(fluorescence in situ hybridization,FISH)检测28例原发性涎腺MEC中MAML2基因重排;应用免疫组化EnVision两步法检测CK7、p63、CK5/6、S-100、CD117的表达,并进行诊断及鉴别诊断.结果28例MEC中有17例(14例低级别、3例中级别)MAML2基因重排,检出率为60.7％(17/28),其中包含Warthin瘤样变异型和透明细胞变异型.MAML2基因重排与肿瘤部位、病理分级密切相关,发生在腮腺、低级别的MEC中MAML2基因重排发生率显著增高(P＜0.05),MAML2基因重排与患者年龄、性别、肿瘤最大径、淋巴结有无转移、临床分期无相关性(P＞0.05).结论MAML2基因重排与肿瘤发生部位、病理分级密切相关,MAML2基因重排阳性可以辅助诊断变异型MEC.

目的 探讨原发性卵巢透明细胞癌(ovarian clear cell carcinoma,OCCC)的临床病理学特点.方法 回顾性分析2010年2月 ～2018年10月安徽省立医院经妇科手术切除的30例OCCC临床病理资料.根据病理形态是否源于内膜样囊肿(endom-etrioid cyst,EC)分成EC组和非EC组,并对两组及早期和进展期OCCC临床病理特征进行比较分析,并复习相关文献.结果 EC组腹水及腹/盆腔转移的发生率比非EC组显著减少(P=0.003,P=0.008).此外,EC组FIGO分期为早期的多于非EC组(P=0.066).两组在年龄、单双侧、最大径、CA125、淋巴结转移及存活方面差异无显著性(P>0.05).早期OCCC患者腹水、腹/盆腔转移及淋巴结转移发生率明显少于进展期OCCC(P<0.05),与其他临床病理特征无关.结论 早期OCCC预后较好.与非EC组相比,起源于EC组的患者预后相对较好.

(1) To investigate associations between single nucleotide polymorphisms (SNPs) in osteopontin (OPN) and its receptor—cluster of differentiation 44 (CD44) genes and gastric cancer susceptibility. (2) To explore the correlation of OPN and CD44 expression of gastric cancer.

The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals [95% CI]=0.643–0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021, OR=2.882, 95% CI=1.173–7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001), tumor location (P=0.007), histological type (P=0.005) and differentiation (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population.

Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of cancers. Here, we investigated the associations between variants of these three genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1 SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case–control study of patients with gastric cancer and cancer-free controls in the Chinese Han population. We found associations of certain variants with location of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented significant associations with a decreased risk of cardia cancer (P = 0.024, OR 0.605, 95 % CI 0.390–0.938; P = 0.015, OR 0.699, 95 % CI 0.522–0.935; and P = 0.022, OR = 0.703, 95 % CI 0.519–0.951, respectively). ADIPOQ rs16861205 with minor allele A displayed an association with an increased risk of body cancer (P = 0.010, OR 1.821, 95 % CI 1.148–2.890). Further stratified analysis of the patients indicated that there were significant correlations for rs1342387A/G (P = 0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P = 0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P = 0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016), rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption; rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food; rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G (P = 0.029) with gender. Adiponectin expression significantly correlated with gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019) and invasion depth of primary tumor (P = 0.024). Our data suggested that variants of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer subtypes. These findings need to be validated in a larger panel of samples from distinct populations.

Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E-selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E-selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13-7.12). C allele of E-selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E-selectin variant did not affect the protein expression. E-selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor-node-metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36-2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20-2.35, respectively). Interleukin-4 receptor (IL-4R) variant rs2107356 presented negative correlations to E-selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E-selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E-selectin protein would promote progression of gastric cancer.

To date, few association analyses with regard to gene variants and expression of vascular endothelial growth factor (VEGF) in gastric carcinoma (GC) have been reported. We hypothesized the variants might also affect susceptibility to GC. To evaluate the correlation of VEGF variants with risk and clinicopathological characteristics of this disease in China, we detected fourteen single nucleotide polymorphisms (SNPs) of VEGF gene in 311 patients with gastric carcinoma and 425 age and gender-matched controls by using Sequenom iplex. We investigated expression of VEGF in combination with cyclooxygenase-2 (COX-2) in 238 tissues samples of the cases by tissue microarray (TMA) and immunohistochemistry (IHC). There were no significant differences in genotype, allele and haplotype distributions of the 14 VEGF SNPs between the cases and the controls. However, we found that there were significant clinicopathological correlations of the rs3024994C/T with gender, the rs3025021C/T with tumor size, the rs3025039C/T with tobacco smoking, the rs3025030G/C with tumor location, tobacco smoking and alcohol drinking (P<0.05, respectively). A/A genotype (P=0.050, OR=0.39, 95%CI=0.15-1.00) and A allele (P=0.024, OR=0.64, 95%CI=0.43-0.94) of the rs833052 significantly reduced the VEGF expression and T allele of the rs3025007 increased the VEGF expression (P=0.017, OR=1.70, 95%CI=1.10-2.61) when compared to the C allele of both the variants, respectively. The VEGF expression displayed a significant association with COX-2 (rs= 0.178, P=0.006). We concluded that none of the 14 SNPs of VEGF gene was significantly associated with the susceptibility to GC. Both VEGF and COX-2 showed close correlations with invasion and progression in advanced GC.

Purpose To explore the correlation between the single nucleotide polymorphisms(SNPs) of VEGF and susceptibility of gastric cancer in Anhui region,and to investigate the relationship among SNPs in VEGF gene,clinicalpathological parameters and expression of vascular endothelial growth factor(VEGF) and cyclooxygenase-2(COX-2) in gastric cancer tissues.Methods VEGF rs3025039 and rs3025021 in 238 patients with gastric cancer and 425 controls from Anhui Province were genotyped by using gene sequencing instrument.Expression of VEGF and COX-2 in 238 cases of gastric cancers and 30 adjacent noncancerous tissues of the patients were detected by tissue microarray-based immunohistochemistry.Results VEGF rs3025039TT and rs3025021CT genotype significantly increased or decreased the risk of gastric cancer(P=0.047,OR=2.86,95% CI=1.01～8.08;P=0.032,OR=0.65,95% CI=0.44～0.96,respectively).Gastric cancers revealed significant expression of both VEGF and COX-2(62.6% and 61.8%,respectively) compared to the adjacent tissues(26.7% with P=0.000 and 36.7% with P=0.008,respectively).There were statistically significant correlations of the expression of VEGF and COX-2 to tumor biological behaviors of gastric cancers: clinical TNM stage,tumor size,invasive depth,lymph node metastasis,clinical stage(only VEGF) and histological type(only COX-2)(P=0.001～0.05).Expression of VEGF was positively correlated with that of COX-2(rs=0.178,P=0.006).There were no relationship among VEGF gene polymorphisms,clinicopathological parameters and expression of VEGF and COX-2 in gastric cancer tissues,excepting that VEGF rs3025021 was significantly correlated with tumor size(P=0.026).Conclusions VEGF rs3025039 and rs3025021 polymorphisms affect the susceptibility of gastric cancer in Anhui region,but do not correlate with the expression of VEGF.The two proteins of VEGF and COX-2 are strongly associated with the invasion of gastric cancer,and might play a synergistic role in the progress of gastric cancers.

Recently, investigation of immune eytokines and their single nucleotide polymorphisms (SNPs) has become a focus research in the clinical genetic epidemiological studies of gastric cancer. Studies reveal that some of SNPs in cytokines independently or jointly with Helicobacter pylori increase the risk or sus-ceptibility of gastric cancers or precancerous lesions.