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.

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.

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.

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.

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.

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.

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。

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。

淋巴结切除总数及阳性转移个数对贲门癌患者术后生存期的影响

目的:探讨贲门癌手术切除淋巴结总数及阳性转移个数对患者术后生存的影响。方法:通过问卷调查、入户和(或)电话随访及住院病理结果核查,采用Kaplan-Meier法绘制生存曲线,Log-rank检验比较单纯手术治疗的1955例贲门癌患者不同淋巴结切除总数和不同阳性转移个数的生存期。结果:1386例淋巴结转移阳性的患者中,淋巴结切除数目为1～3枚,4～6枚,7～9枚,≥10枚时,中位生存期分别为30、35、39和63个月,Log-rank检验,χ2=20.626,P<0.001。569例淋巴结转移阴性的患者中,淋巴结切除数目为1～2枚,3～4枚,5～6枚,≥7枚时,中位生存期分别为156、168、212和202个月,Log-rank检验,χ2=5.077,P=0.166。阳性淋巴结转移个数为1枚、2枚、3枚和大于3枚时,中位生存期分别为48、41、36和27个月,Log-rank检验,χ2=25.771,P<0.001。结论:淋巴结切除总数的增加可延长患者术后生存期;阳性转移个数多可缩短患者术后生存期。

1982年至1999年食管癌、贲门癌低发区和高发区患者TNM分期比较

目的探讨1982年到1999年18a间中国北方城市食管、贲门癌城市低发区与农村高发区居民中新发食管癌与贲门癌患者的肿瘤TNM分期分布特征。方法根据北京同仁医院和河北磁县人民医院的病例资料记录,动态分析这2个医院18a间首次确诊时的食管癌和贲门癌TNM分期,并依据TNM分期,将患者分为早期(TNM0和Ⅰ期),中期(TNMⅡa和Ⅱb期)及晚期(TNMⅢ和Ⅳ期)。结果18a间农村居民患者首次确诊的4928例食管癌(3074例)和贲门癌(1854例)中,早期患者仅占5%和2%,95%以上的患者均为中、晚期。城市居民患者首次确诊的751例食管癌和贲门癌患者中,早期食管癌(14%)和早期贲门癌(10%)均略高于农村患者(P<0.05),但是城市患者中,90%的贲门癌和86%的食管癌患者仍为中、晚期。结论城市低发区和农村高发区首次就诊的食管癌和贲门癌患者仍以中、晚期为主,这是导致食管贲门癌预后差、死亡率高的主要原因。

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。

河南食管癌高发区食管贲门双源癌粘蛋白1、C-erbB2蛋白的表达

目的 :探讨同一个体食管贲门双源癌组织粘蛋白 1(MUC1)和C erbB2蛋白变化的特征及其意义。方法 :采用免疫组化卵白素 生物素 过氧化物酶复合物 (ABC)法和组织病理学方法 ,分析河南食管癌高发区 2 5例双源癌患者 (同时发生食管鳞癌和贲门腺癌 )MUC1和C erbB2蛋白的表达状况。结果 :2 5例患者食管鳞癌和贲门腺癌组织均出现不同程度的MUC1和C erbB2蛋白的阳性表达。食管癌 :MUC1,C erbB2免疫阳性率分别为 80 %(2 0 / 2 5 ) ,2 0 % (5 / 2 5 ) ;贲门癌 :分别为 72 % (18/ 2 5 ) ,4 8% (12 / 2 5 ) ,且免疫反应类型均主要为弥漫型。MUC1,C erbB2蛋白在食管和贲门双源癌肿瘤组织中具有很高的一致性改变 ,一致性改变率分别为 92 %、6 4 %。结论 :食管和贲门双源癌存在较高的MUC1和C erbB2蛋白一致性改变 。

食管贲门双源癌组织中Rb蛋白的表达

目的:探讨食管贲门双源癌组织中Rb蛋白表达的变化特征及其意义。方法:采用免疫组化ABC法和组织病理学方法,分析河南食管癌高发区林州市30例食管贲门双源癌患者Rb蛋白的表达状况。结果:在30例双源癌患者中,食管鳞癌和贲门腺癌组织中Rb阳性率分别为46.7%(14/30)和40%(12/30),差异无统计学意义(χ2=0.272,P>0.05)。食管和贲门癌组织Rb一致阳性率为36.7%(26/30),一致阴性率为50%(15/30),食管鳞癌和贲门腺癌组织中Rb的表达相关(P<0.05)。结论:该地区食管癌和贲门癌存在较高的Rb一致性变化,提示二者可能具有相似的发病因素和分子机制。

河南食管癌高发区食管和贲门癌组织中PTEN蛋白的表达

目的 :探讨PTEN蛋白在食管鳞癌和贲门腺癌组织中表达变化及其与细胞分化程度及淋巴结转移的关系。方法 :采用免疫组化卵白素 生物素 过氧化物酶复合物 (ABC)法和组织病理学方法 ,分析河南食管癌高发区林州市 14 1例食管鳞癌和贲门腺癌患者PTEN的表达状况。结果 :食管鳞癌和贲门腺癌PTEN阳性率分别为 4 7%(34/73)和 4 3% (2 9/6 8)。随着肿瘤分化程度的升高 ,PTEN蛋白的表达有增高的趋势 ,淋巴结转移组PTEN免疫阳性率较无淋巴结转移组高 ,但统计分析未发现PTEN免疫阳性反应率与分化程度和淋巴结转移间存在相关性(P均大于 0 .0 5 )。结论 :河南食管癌高发区食管鳞癌和贲门腺癌存在一致的PTEN蛋白变化 ,提示

贲门癌癌旁组织肠上皮化生检测

目的:探讨贲门癌(GCA)癌旁肠上皮化生(IM)的组织学和组织化学特征及其与病变的关系。方法:采用爱显蓝-雪夫试剂染色和高铁二胺-爱显蓝染色2种方法分析408例河南GCA高发区GCA癌旁组织IM的分布特征。结果:GCA癌旁IM的检出率为32%(130/408),Ⅰ、Ⅱ和Ⅲ型IM所占比例分别为65%、16%和19%,Ⅰ型多于其他2型(χ2=86.146,P<0.05)。IM伴不典型增生的比例(88%)高于伴慢性浅表性胃炎(13%)和慢性萎缩性胃炎(30%)(P<0.05)。结论:GCA癌旁IM的发生率随癌前病变的加重逐渐升高,提示其可能是一种重要的GCA癌前病变。

转录因子SOX7基因在贲门腺癌中的异常表达及其甲基化状态

目的:检测贲门腺癌(gastric cardia adenocarcinoma,GCA)组织及相应癌旁非肿瘤组织中Y性别决定区基因7(sex determining region Y-box 7,SOX7)的甲基化状态及其对SOX7 mRNA表达、Wnt通路中心因子β-catenin异质表达的影响及与临床病理特征之间的相关性。方法:选择河北医科大学第四医院胸外科2006-2012年手术切除的GCA及癌旁组织各130例,应用甲基化特异性PCR(methylation specific PCR,MSP)、RT-PCR分别检测130例GCA及癌旁组织中SOX7基因的甲基化状态及其mRNA表达情况,应用免疫组织化学方法检测标本中β-catenin蛋白的表达。分析SOX7的甲基化状态与临床病理特征、SOX7 mRNA表达、β-catenin蛋白的异质表达及上消化道肿瘤家族史(upper gastrointestinal cancers,UGIC)的关系。结果:GCA组织中SOX7的甲基化率显著高于癌旁组织为[57.7%(75/130)vs 30.8%(40/130),P<0.01],其高甲基化仅与肿瘤患者的淋巴结转移情况有关(P<0.05),与肿瘤组织的病理分级及临床分期均无关(P>0.05)。GCA组织中SOX7mRNA的表达量明显低于癌旁非肿瘤组织[(0.414±0.054)vs(0.695±0.034),P<0.01〗],其β-catenin蛋白的异质表达率显著高于癌旁组织(85.4%vs 43.1%,P<0.01);GCA组织中SOX7基因mRNA表达情况及β-catenin蛋白的异质表达率均与该基因的甲基化状态有关(P<0.05),并且SOX7基因的甲基化状态与贲门癌患者的上消化道家族史密切相关(P<0.01)。结论:Cp G岛甲基化是SOX7基因表达下调的机制之一,并可能通过Wnt/β-catenin信号转导通路的激活在贲门腺癌的发生中扮演着重要的角色。