Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population

Objective： To investigate the association between gastric cardia adenocarcinoma （GCA） and ten functional single nueleotide polymorphisms （SNPs）, including TPY3BPI rs560191 G〉C, CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A, and six C1 orf 10/CRNN variants. We performed a hospital- based case-control study to evaluate the genetic effects of these SNPs. Methods： Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom- by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results： When the TP^3BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A or the six ClorflO/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conciusions： The results demonstrated that the functional polymorphism TP53BPI rs560191 G〉C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well- designed studies and further functional investigations are needed to confirm our findings.

Gastric cardia adenocarcinoma in Taiwan Residents men:Positive associations due to selection bias

The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood.Environmental factors such as Helicobacter pylori(H.pylori) infection and diet have been hypothesized to play a role in the recently increased risk of this disease,but additional studies are needed.In conducting studies to establish the relationship between potential risk factors and gastric cardia adenocarcinoma,it is necessary to carefully consider the role of bias.In a recently published study,the reported associations between H.pylori as well as post-meal physical exertion and gastric cardia adenocarcinoma may have been greatly influenced by selection bias.

Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.

Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas

Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

Pathological factors affecting gastric adenocarcinoma survival in a Caribbean population from 2000-2010

AIM: To investigate pathological factors related to long term patient survival post surgical management of gas-tric adenocarcinoma in a Caribbean population.METHODS: This is a retrospective, observational study of all patients treated surgically for gastric adenocarci-noma from January 1st 2000 to December 31 st 2010 at The University Hospital of the West Indies, an urban Jamaican hospital. Pathological reports of all gastrecto-my specimens post gastric cancer resection during the specified interval were accessed. Patients with a final diagnosis other than adenocarcinoma, as well as pa-tients having undergone surgery at an external institu-tion were excluded. The clinical records of the selected cohort were reviewed. The following variables were analysed; patient gender, patient age, the number of gastrectomies previous performed by the lead surgeon, the gross anatomical location and appearance of the tumour, the histological appearance of the tumour, infil-tration of the tumour into stomach wall and surround-ing structures, presence of Helicobacter pylori and the presence of gastritis. Patient status as dead vs alive was documented for the end of the interval. The effect of the aforementioned factors on patient survival were analysed using Logrank tests, Cox regression models, Ranksum tests, Kruskal-Wallis tests and Kaplan-Meier curves.RESULTS: A total of 79 patients, 36 males and 43 fe-males, were included. Their median age was 67 years(range 36-86 years). Median survival time from surgery was 70 mo with 40.5% of patients dying before the termination date of the study. Tumours ranged from 0.8 cm in size to encompassing the entire stomach speci-men, with a median tumour size of 6 cm. The median number of nodes removed at surgery was 8 with a maximum of 28. The median number of positive lymph nodes found was 2, with a range of 0 to 22. Patients' median survival time was approximately 70 mo, with 40.5% of the patients in this cohort dying before the terminal date. An increase in the incidence of cardiac tumours was noted compared to the previous 10 year interval(7.9% to 9.1%). Patients who had serosal involvement of the tumour did have a significantly shorter survival than those who did not(P = 0.017). A significant increase in the hazard ratio(HR), 2.424, for patients with circumferential tumours was found(P = 0.044). Via Kaplan-Meier estimates, the presence of venous infiltration as well as involvement of the circum-ferential resection margin were found to be poor prog-nostic markers, decreasing survival at 50 mo by 46.2% and 36.3% respectively. The increased HR for venous infiltration, 2.424, trended toward significant(P = 0.055) Age, size of tumour, number of positive nodes found and total number of lymph nodes removed were not useful predictors of survival. It is noted that the results were mostly negative, that is many tumour character-istics did not indicate any evidence of affecting patient survival. The current sample, with 30 observed events(deaths), would have about 30% power to detect a HR of 2.5.CONCLUSION: This study mirrors pathological factors used for gastric cancer prognostication in other popu-lations. As evaluation continues, a larger cohort will strengthen the significance of observed trends.

信迪利单抗联合奥沙利铂和替吉奥治疗贲门腺癌致免疫性心肌炎并文献分析

报道1例64岁女性患者因贲门腺癌行信迪利单抗(200 mg,d1)+奥沙利铂(200 mg,d1)+替吉奥(60 mg,bid,d1~14)的3周治疗方案。患者在第2周期治疗的第7天出现后背疼痛,心肌损伤标志物升高,心电图Ⅲ、aVF导联可见异常Q波,T波低平。经冠脉CT检查后排除冠状动脉粥样硬化所致冠心病,诊断为免疫性心肌炎。停用抗肿瘤药物,给予甲泼尼龙治疗9 d后症状缓解,心肌损伤标志物明显下降。免疫性心肌炎是信迪利单抗罕见且严重的不良反应,临床应用信迪利单抗时应密切监测心肌损伤标志物的变化和患者的症状、体征。

贲门腺癌组织中淋巴细胞活化基因-3的表达及临床意义

目的探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)组织中淋巴细胞活化基因-3(lymphocyte activation gene-3,LAG-3)的表达与临床病理特征和生存期的关系。方法收集2015年1月至2020年12月濮阳市人民医院101例术后病理证实为GCA患者的病理组织蜡块及临床资料,随访其生存状况,采用免疫组织化学方法检测LAG-3的表达情况,采用Kaplan-Meier法及log-rank检验对数据进行分析,并绘制生存曲线。结果LAG-3主要定位在GCA组织的肿瘤浸润淋巴细胞(tumor infiltrating lymphocytes,TILs)的细胞质和细胞膜上,阳性表达率为53.5%(54/101),LAG-3表达与年龄、性别、大体分型、分化程度、肿瘤直径、浸润深度、淋巴结转移情况、TNM分期无明显相关性(P>0.05);LAG-3阳性组较LAG-3阴性组生存期短(P=0.0099)。结论LAG-3的表达与GCA的临床病理特征之间无明显关联,其阳性表达患者预后差。

食管癌与贲门癌患者的临床症状对比分析

目的比较食管癌和贲门癌患者常见的临床症状类型与临床病理特点,分析两者临床症状的相似性。方法从《省部共建食管癌防治国家重点实验室临床诊疗、病理和随访信息数据库》,收集2019年11月至2020年1月间经胃镜联合病理活检确诊并进行根治性手术的食管癌患者380例、贲门癌患者177例,对两组患者的临床症状等信息进行整理和统计学比较,分析两种肿瘤患者的临床症状及病理特点。结果食管癌和贲门癌患者的临床症状可规范分类为13种,常见的依次为吞咽不适(68.04%)、腹部不适(11.49%)、消化道出血(3.77%)、胃食管反流(3.59%)等,其中吞咽不适、腹部不适、消瘦乏力3种临床症状在两类患者中的分布差异有统计学意义(P<0.05),但吞咽/腹部不适相关症状在两组患者之间无显著性差异(P>0.05)。胃食管反流和上消化道出血症状都多见于中晚期食管癌和贲门癌(P>0.05)。无症状食管癌患者多为早期,而无症状贲门癌患者以中晚期多见(P<0.01)。结论食管癌和贲门癌在流行病学特征、临床症状上表现出密切的联系,临床症状具有明显的相似性。

Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

Background In China, esophageal squamous cell carcinoma （ESCC） and gastric cardia adenocarcinoma （GCA） share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males （P 〈0.000） and 25.0%, 22.3%, 23.9%, and 9.8% in females （P 〈0.0001）. Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females （ both P 〈0.0001） for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2：1 for upper, middle, lower third ESCC and GCA （P〈0.0001）. For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

An Asian population-based survival analysis of patients with distal esophageal and gastric cardia adenocarcinomas

Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus （DE） and gastric cardia （GC）. It is controversial whether these tumors are the same entity and whether they have the same survival rates. Patients with DE and GC adenocarcinomas have a similar survival rate in the US; however, data are lacking in Asian countries. Therefore, we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients. Methods A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the study. We identified patients with adenocarcinomas of the DE （DE group, n=91） and GC （GC group） （n=118）, We performed an unadjusted survival analysis using the Kaplan-Meier method, and used a Cox proportional hazards regression model to adjust for potential confounding covariates. Results We found no significant difference between the overall survival of the DE and GC groups. The 3-year survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates were 27.9% and 30.2%, respectively （P=0.162）. We found no significant difference in early staging, advanced staging, different T staging, and different N staging, between the groups. Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival. Conclusions Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population. Both post-operative N staging and AJCC staging are prognostic factors.

LINC00997在胃贲门腺癌中表达的临床意义及其对SGC7901细胞迁移、侵袭和EMT的影响

目的:检测LINC00997在胃贲门腺癌(GCA)组织及胃癌细胞中的表达,分析其表达与患者临床病理特征和预后的关系,探讨敲减LINC00997对胃癌SGC7901细胞迁移、侵袭及上皮间质转化(EMT)的影响。方法:基于TCGA和GTEx数据库分析LINC00997在胃癌组织中的表达及其与患者预后的关系。应用qPCR法检测68例GCA组织和相应癌旁组织以及胃癌细胞中LINC00997的表达水平,分析其表达与患者临床病理特征及预后的关系。通过划痕愈合、Transwell侵袭实验分别检测敲减LINC00997对SGC7901细胞迁移和侵袭的影响,qPCR法和WB法检测敲减LINC00997对EMT相关标志物E-cadherin、N-cadherin及vimentin表达的影响。结果:LINC00997在胃癌组织中的表达水平显著高于癌旁组织(P<0.05),且LINC00997高表达组患者的OS及DFS显著低于LINC00997低表达组患者(P<0.01或P<0.05)。在68例在GCA组织中,LINC00997的表达水平显著高于癌旁组织(P<0.01),其表达与患者淋巴结转移、TNM分期及OS相关联(P<0.05或P<0.01)。敲减LINC00997的SGC7901细胞的迁移和侵袭能力均显著降低(均P<0.01),细胞中E-cadherin的表达显著升高,N-cadherin、vimentin的表达均显著降低(P<0.05或P<0.01)。结论:LINC00997在GCA组织和胃癌细胞中高表达,其高表达可能促进了胃癌细胞的迁移、侵袭及EMT进程,有望成为GCA患者预后评估的分子标志物。

miR-133a-5p对胃贲门腺癌细胞增殖、黏附和M1型巨噬细胞极化的影响

目的:探究miR-133a-5p调控血清外泌体源性纤连蛋白1(fibronectin1,FN1)的表达对胃贲门腺癌(gastric cardia adenocarcinoma,GCA)细胞增殖、黏附和M1型巨噬细胞极化的影响。方法:借助GEO数据库分析GCA组织中的差异表达基因,进行功能富集分析。采用qPCR检测FN1在GCA组织、血清、血清外泌体和细胞中的表达。向GCA患者血清外泌体中转染FN1的过表达载体及其对照质粒,向HGC-27细胞中转染miR-133a-5p模拟物及其对照,将转染后的HGC-27细胞和外泌体共培养,再将此细胞与THP-1细胞共培养。采用CCK-8和细胞黏附实验分别检测各组HGC-27细胞的增殖和黏附情况,WB法、ELISA分别检测细胞中CD86、iNOS的水平以及对巨噬细胞分泌IL-6、IL-1β的影响。采用双荧光素酶报告基因实验验证FN1 mRNA和miR-133a-5p之间的相互作用关系。结果:与健康人对照组相比,GCA组织、血清、血清外泌体和细胞中的FN1表达水平显著上调(均P<0.05),FN1高表达的血清外泌体与GCA患者的TNM分期(P=0.0329)和淋巴结转移有关联(P=0.0127)。富含FN1的血清外泌体能够被GCA细胞内化,与过表达FN1的外泌体共培养能够提高HGC-27细胞的增殖和黏附能力,抑制THP-1细胞中IL-6、IL-1β、CD86和iNOS的表达,抑制M1型巨噬细胞极化(P<0.05或P<0.01)。miR-133a-5p在GCA组织和细胞中较对照组显著降低,可负调控FN1的表达,过表达miR-133a-5p能够通过降低GCA细胞增殖和黏附能力,促进IL-6、IL-1β、CD86和iNOS的表达,部分逆转FN1对GCA细胞恶性行为的促进作用(P<0.05或P<0.01)。结论:miR-133a-5p可通过抑制血清外泌体分泌FN1对GCA细胞的恶性行为起抑制作用,对M1型巨噬细胞极化起促进作用。

河南贲门癌高发区贲门癌发生部位分析

目的：分析河南贲门癌高发区贲门癌发生部位及其年龄和性别分布特征,加深对贲门癌,食管/贲门交界部腺癌以及食管下段原发性腺癌分类和分型的认识。方法：以食管鳞状上皮和贲门柱状上皮交界部的齿状线为参照,将贲门癌区分为4种类型A型肿瘤全部位于齿状线下方;B型肿瘤2/3位于齿状线下方;C型肿瘤1/2位于齿状线下方;D型肿瘤1/3位于齿状线下方。分析比较河南贲门癌高发区595例贲门癌患者肿瘤发生部位的分布特征。结果：595例贲门癌患者中,男女性比例为3.5∶1。男性和女性贲门癌发生部位均以A型和B型为主（〉95%）,高于C型和D型（P〈0.05）。青年贲门癌患者以A型为主（78%）,高于中老年患者（P〈0.05）。除男性和女性30-年龄段A型多于B型（P〈0.05）,女性60-年龄段B型多于A型（P〈0.05）外,其余男性和女性各年龄段A型和B型间差异均无统计学意义（P〉0.05）。结论：河南贲门癌高发区贲门癌95%以上属A型和B型,主要发生于解剖学贲门部位,与西方国家食管/贲门交界部腺癌发生部位明显不同,建议将贲门癌作为一种独立的疾病进行研究。

贲门癌组织GSTM1,GSTT1和GSTP1基因多态变化

目的 :探讨河南林州地区贲门癌组织中 3种Ⅱ期代谢酶基因GSTM1,GSTT1及GSTP1基因多态性变化 ,进一步深入了解该地区贲门癌高易感性分子基础。方法 :利用multiplex PCR、PCR RFLP检测 19例手术切除贲门腺癌组织及 72例正常对照组织 (颊粘膜细胞和血细胞 )中代谢酶基因GSTM1、GSTT1、GSTP1多态性改变。结果 :贲门腺癌与正常对照组织中GSTM1纯合缺失基因型分别占 37%和 39% ,该基因型未明显增加对贲门癌的易感性 (OR =0 .6 9) ;GSTT1纯合缺失基因型分别占 5 3%和 39% ,该基因型可能与贲门癌易感性增高有关 (OR =2 .38) ;GSTP1的Ile/Val和Val/Val基因型合并在一起分别占 2 6 %和 4 2 % ,Val等位基因能降低个体贲门癌的易感性 (OR =0 .4 1)。结论 :GSTM1基因多态对贲门癌易感性无明显影响 ,而GSTT1和GSTP1基因多态与贲门癌易感性有关。

GADD45A基因在人贲门腺癌组织中的异常甲基化和表达及其临床意义

目的:探讨生长阻滞和DNA损伤诱导45A(growth arrest and DNA-damage-inducible 45 alpha,GADD45A)基因在贲门腺癌(gastric cardia adenocarcinoma,GCA)中的异常甲基化及表达,并探讨其临床意义。方法:选取河北医科大学第四医院2004-2007年期间GCA患者组织标本(138例)。分别应用亚硫酸氢盐测序法(bisulfite sequencing,BS-Seq)、亚硫酸氢盐转换-甲基化特异性聚合酶链式反应(bisulfite conversion-methylation specific polymerase chain reaction,BS-MSP)、RT-PCR和免疫组织化学法检测GADD45A基因在GCA组织及癌旁正常组织中的甲基化、GADD45A mRNA及蛋白表达的情况。结果:GADD45A远端启动子区的4个CpG位点在GCA组织中的甲基化率[44.93%(62/138)]显著高于癌旁正常组织[0.00%(0/138)](P<0.01),且在Ⅲ期和Ⅳ期GCA组织中的甲基化率显著高于Ⅰ期和Ⅱ期GCA组织(P<0.05),但GADD45A在GCA组织中的甲基化与患者的年龄、性别及病理分化程度无关(P>0.05)。GADD45A近端启动子(region 2)及第一外显子区(region 3)的CpG岛在GCA及癌旁组织中均未检测到甲基化。GCA组织中GADD45A mRNA和蛋白阳性表达率显著低于癌旁正常组织[(0.35±0.15)vs(0.78±0.26),42.75%vs 71.01%,均P<0.05],且与其远端启动子区4个CpG位点的甲基化状态之间有明显的相关性(r=-0.52,P<0.01)。结论:GADD45A基因远端启动子区的4个CpG位点的高甲基化导致的基因沉默可能与GCA中GADD45A基因表达降低有关。

贲门癌癌旁和无症状人群贲门黏膜活检组织肠上皮化生检测

目的:探讨贲门癌癌旁组织及无症状人群贲门黏膜活检组织肠上皮化生(IM)的分布特征。方法:采用艾显蓝-雪夫(AB-PAS)和高铁二胺-艾显兰(HID-AB)黏液组织化学染色法,对河南贲门癌高发区70例贲门癌癌旁组织和320例无症状人群贲门黏膜活检组织中的IM进行检测。结果:贲门癌癌旁组织的IM检出率38.5%(27/70),高于无症状人群贲门黏膜活检组织中的IM检出率4.4%(14/320)(χ2=71.3945,P<0.01)。贲门癌癌旁组织IM不完全型占92.6%(25/27),完全型IM占7.4%(2/27);无症状人群贲门黏膜的IM不完全型占7.1%(1/14),完全型IM占92.9%(13/14);2者比较,差异有统计学意义(χ2=29.0157,P<0.01)。贲门癌旁组织的IM大肠型占59.2%(16/27),小肠型占40.8%(11/27);无症状人群贲门黏膜的IM小肠型占92.9%(13/14),大肠型占7.1%(1/14);2者比较,差异有统计学意义(χ2=10.3173,P<0.01)。结论:IM可能是河南贲门癌高发区贲门癌癌前病变的一种重要表现形式;不完全型和大肠型IM可能是贲门癌前病变的独特组织学类型。

食管癌高发区队列内镜筛查随访分析

目的:分析食管癌高发区大人群内镜加碘染色筛查敏感性和漏诊率。方法:根据2002年5月河北省磁县40～65岁2013例内镜队列筛查样本,通过以2006年1月～3月随访所证实发生的食管鳞癌、贲门腺癌和胃癌病例为数据计算敏感性和漏诊率。结果:在内镜筛查后的6个月～36个月中,随访证实新发生食管鳞癌2例,贲门腺癌4例,胃窦腺癌1例,其他癌6例,死因不详1例。失访11例,随访率99.4%。经计算内镜筛查食管鳞癌灵敏度97.1%,漏诊率2.9%;贲门腺癌分别为80.0%和20.0%。结论:食管癌高发区内镜加碘染色筛查,贲门癌的灵敏度低于食管癌。

贲门癌组织微粒体环氧化物羟化酶基因多态变化

目的 :探讨贲门癌组织微粒体环氧化物羟化酶 (mEH)基因多态性改变 ,进一步深入了解贲门癌高易感性分子基础。方法 :利用PCR和PCR SSCP方法对 19例贲门腺癌和 72例正常对照组织mEH基因多态性进行了检测。结果 :贲门腺癌和正常对照组织中 ,mEH的Arg/His和His/His基因型合并在一起分别占 16 %和 15 % ,His等位基因对贲门癌易感性并无明显影响 (OR =0 .72 ) ;mEH的His/Tyr和Tyr/Tyr基因型合并在一起分别占 5 8%和 5 7% ,Tyr等位基因并未影响个体对贲门癌的易感性 (OR =0 .92 )。结论 :mEH基因多态对贲门癌易感性无明显影响。