胃粘膜肠化生细胞增殖状态分型的研究

应用免疫组织化学方法检测２３０例胃粘膜病变中增殖细胞核抗原的表达情况，计算细胞增殖指数，探讨胃粘膜肠化生的增殖状态分型以及肠化生细胞增分型与肿瘤相关基因蛋白产物的关系。结果显示正常或慢性浅表性胃炎，伴肠化生慢性萎缩性胃炎，伴异型增生萎缩性胃炎以及胃腺癌的ＰＩ逐渐增高；差异非常明显。     

胃粘膜肠化生细胞增值状态分型的研究

应用免疫组织化学方法检测230例胃粘膜病变中增殖细胞核抗原（PCNA）的表达情况，计算细胞增殖指数（PI）、探讨胄粘膜肠化生的增殖状态分型以及肠化生细胞增殖分型与肿瘤相关基因蛋白产物的关系。结果显示正常或慢性浅表性胃炎、伴肠化生慢性萎缩性胃炎、伴异型增生萎缩性胃炎以及胃腺癌的PI逐渐增高，差异非常明显（P＜0．0）。根据胃粘膜肠化生细胞的PI分布，进行畅化生细胞的增殖状态分型：高增殖状态型为PI≥40，中增殖状态型为20≤P＜40，低增殖状态型为PI＜20。此分型与各类胃粘膜病变显示较好的相关性，低增殖状态型为正常或基本正常胃粘膜，中增殖状态型为胃粘膜良性病变，高增殖状态型为胃粘膜癌前病变。高增殖状态型肠化生中肿瘤相关基因蛋白产物rasp21、EGFR、h-met的表达以及叵型肠化生的检出率显著高于中、低增殖状态型肠化生（P＜0．05）。提示高增殖状态型肠化生细胞基因表达的异常率增高，且细胞分化不良，更具胃癌前病变的特征。     

测定不同类型肠化生胃粘膜cAMP,DNA和微量元素探索癌变倾向

作者随机抽样观察50例手术切下胃标本粘膜,通过组织化学、放射免疫、自动图象分析仪和能量色散X线分析仪检测,发现①胃粘膜cAMP、Zn、Cu、ZnO与CuO含量,随正常组织至完全性不完全性、小肠型至结肠型、至癌组织的顺序递减。而DNA则随此顺序递增(P<0.05～0.001);②这些物质在不完全性绪肠型肠化生与癌组织间量变无显著性差异,预示前者有癌变倾向。     

胃粘膜肠上皮化生与胃癌的关系

胃粘膜肠上皮化生(简称肠化)的分型标准以及与胃癌的关系尚不统一,目前仍存争议。近年,国内外学者应用粮液组化方法将肠化分为不同的亚型来探讨肠化与胃癌的关系,多数认为含有硫酸粘液的不完全型肠化在胃癌的发生中有特殊意义。作者应用结肠卵巢肿瘤抗原(简称COTA),一种与肿瘤性结肠上皮细胞有关的粘液性抗原,对一组胃癌和各种不同病变的肠化组织作免疫组化染色,观察COTA在这些组织中的分布,探讨肠化与胃癌的关系。     

PCNA在胃粘膜肠上皮化生、异型增生、和胃癌中的表达及意义

目的　观察增殖细胞抗原 (PCNA)在胃粘膜肠上皮化生、异型增生及胃癌中的表达情况 ,评估癌前病变的发展趋势。方法　免疫组织化学方法。结果　PCNA在细胞核内表达 ,从肠上皮化生、异型增生到胃癌呈递增趋势 ,在肠上皮化生表现为轻度表达 ,异型增生以中度为主 ,而胃癌多呈重度和过度表达。结论　PCNA在胃粘膜不同疾病细胞核内的表达 ,反映了细胞增殖状态和生长速度 ,有助于判断肠上皮化生、异型增生的发展趋势及胃癌的预后     

原发性肺癌p53蛋白,增殖细胞核抗原表达及DNA含量与预后的关系

目的探讨ｐ５３蛋白、增殖细胞核抗原（ＰＣＮＡ）在肺癌中表达的特征、相关性及与ＤＮＡ含量和预后的关系。方法应用免疫组织化学方法检测原发性肺癌组织标本ｐ５３蛋白和ＰＣＮＡ的表达，并用图像分析技术测定ＤＮＡ含量。结果ｐ５３蛋白阳性表达组ＤＮＡ含量（８．９１Ｃ）和ＰＣＮＡ半定量分级（Ｉ～Ⅳ级例数为９，１３，１２，１０，下同）显著高于ｐ５３蛋白阴性组（６．６０ｃ）（１４，１５，７，２）在肺腺癌，半年内死亡组ｐ５３蛋白阳性表达率（１１／１５）和ＰＣＮＡ半定量分级（２，５，４，４）显著高于５年以上生存组（７／１９）（１０，６，１，２），且两者表达与淋巴结转移有显著关系；在肺鳞癌，半年内死亡组ＰＣＮＡ半定量分级（４，１，６，２）显著高于５年以上生存组（６，１４，７，０），而ｐ５３蛋白表达与患者预后关系不明显。结论ｐ５３蛋白、ＰＣＮＡ及ＤＮＡ含量间具有显著正相关关系，且ｐ５３蛋白、ＰＣＮＡ表达对于估测肺癌患者的预后有重要意义。     

胃粘膜杯状细胞异型化生与胃印戒细胞癌

近年来,国内外对胃癌超微结构的研究进展很快,已经从进展期胃癌转自早期胃癌和癌前病变的研究。对胃粘膜肠上皮化生的类型及其与各类胃癌发生的密切关系也已经引起关注。但对胃粘膜肠上皮化生中的杯状细胞异型化生与胃印戒细胞癌的关系,尚未见这方面的研究报道。我们在内镜活检配合病理检查过程中,发现胃粘膜杯状细胞化生的异型改变与胃印戒细胞癌有密切的关系,现总结分析报告如下: 材料与方法一、本文收集我院1983年5月—1990年1月经内镜活检病理确诊的胃各类恶性肿瘤     

胃粘膜病变细胞增殖分级的研究

应用免疫组织化学方法检测２３０例胃粘膜病变标本中增殖细胞抗原的表达，计算细胞增殖指数，探讨细胞垃镇发级及其在胃癌发生中的意义。结果显示正常或慢性浅表性胃炎、伴肠化生慢性萎缩民生胃炎、伴异型增生慢笥萎缩性胃炎以主胃腺癌的ＬＩ逐渐增高，差异非常明显。     

乳腺肿瘤增殖细胞核抗原与DNA定量的关系

目的 用单克隆抗体对乳腺肿瘤细胞的增殖细胞核抗的ＰＣＮＡ进行免疫组化标记，并与细胞内ＤＮＡ定量，方法 直方图周期分析加以比较。结果 ＰＣＮＡ阳性细胞的分布在衣性肿瘤及各级乳腺癌不同，其量的表达随恶性程度的增高而增高。经Ｘ＾２检验，Ｐ〈０．０２５，差异显著。结论ＰＣＮＡ中度和蒿度表达的ＤＮＡ含量及异倍体率高于低表达组，但不是明显递增，而是在中度表达组中趋于最高。     

Potential role of aquaporin 3 in gastric intestinal metaplasia

Gastric intestinal metaplasia (GIM) is a pre-cancerous condition and a pivotal step in the formation of gastric cancer (GC). Aquaporin 3 (AQP3) has been found to be expressed in goblet cells rather than mucus-secreting glands. To investigate the characteristics of GIM in non-cancerous tissues adjacent to GC, as well as the expression and role of AQP3 in GIM tissues, 16 patients diagnosed with gastric adenocarcinoma of intestinal type located in the lesser curve of the antrum were consecutively enrolled in this study. A new pathological technology called “gastric mucosal sausage roll” was introduced. GIM was determined according to the updated Sydney system, and AQP3 expression in goblet cells was determined by immunohistochemistry. GIM was found in all stomach specimens, and its incidence increased with progression to GC (P < 0.001). GIM prevalence displayed remarkable association with the distance to GC in the anterior gastric wall tissues (P = 0.016) and tissues toward the cardia (P = 0.014), such that GIM was more common in the areas closer to GC (P < 0.001). AQP3 was found to be expressed in 67.71% of parts with GIM, and AQP3 immunoreactivity was identified more frequently in severe GIM areas (P < 0.001). In short, the incidence and severity of GIM correlated with the distance from GC, and AQP3 was differentially expressed in goblet cells, with most AQP3-positive goblet cells presenting in severe GIM. Together, this study suggests that AQP3 may play an important role in gastric carcinogenesis from GIM.     

Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer

Promoter hypermethylation is an alternative mechanism of gene silencing in human cancers including gastric cancer. While intestinal metaplasia (IM) is generally regarded as a precancerous lesion of the stomach, our study examines the presence of gene promoter hypermethylation in IM of patients with and without gastric cancer. We examined 31 samples of gastric cancer, 36 gastric IM (21 associated with gastric cancer and 15 from noncancer patients) and 10 normal gastric biopsies. Tissues containing foci of IM were carefully microdissected from paraffin-embedded section. Bisulfite-modified DNA was examined for gene promoter hypermethylation in DAP-kinase, E-cadherin, GSTP1, p14, p15, p16, RASSF1A and hMLH1 by methylation-specific-PCR. None of the control gastric tissues had hypermethylation detected, but gene promoter hypermethylation was frequently detected in gastric cancer and IM. The mean number of methylated genes in cancer and IM was 3.0 and 1.4, respectively (p < 0.0001). Methylation in IM from cancer patients was all associated with concurrent methylation in the corresponding tumor samples. The numbers of methylated genes were similar in IM obtained from cancer and noncancer patients. By examining the methylation patterns of these genes, 3 differential methylation patterns were recognized: hypermethylation was more frequent in cancer than in IM (DAP-kinase, p14, p15 and p16); comparable frequencies of methylation in cancer and IM (E-cadherin and hMLH1); and no methylation (GSTP1). Aberrant methylation in tumor-related genes is frequently detected in gastric IM of both cancer and noncancer patients, suggesting their early involvement in the multistep progression of gastric carcinogenesis.     

根除HP感染对胃黏膜炎症和肠腺化生的影响

目的：探讨根除幽门螺杆菌（helicobacter pylori,HP）感染对胃黏膜炎症和肠腺化生（intestinal meta-plasia,IM）的意义。方法：随访119例10年前HP感染的患者,其中62例行根除HP治疗（治疗组）,57例中断治疗或仅接受对症治疗（对照组）,对比其前后HP感染情况、胃黏膜炎症及肠腺化生（IM）的变化情况。结果：10年后对照组中45/57例HP呈阳性（78.94%）;治疗组中15例HP呈阳性（24.19%）,胃炎活动性检出率明显减少与对照组持续HP感染者比较,差异有显著性（P〈0.01）,肠腺化生（IM）的程度也显著减轻（P〈0.05）。结论：HP感染与胃黏膜活动性炎症关系非常密切,根除HP可以减轻胃黏膜的炎症和肠腺化生（IM）程度。     

Risk of gastric cancer among patients with gastric intestinal metaplasia

Plenty of studies have assessed the association between intestinal metaplasia (IM) and gastric cancer risk, while the results were inconsistent. We aimed to assess the risk of gastric cancer among patients with IM. Systematic literature searches were conducted in PubMed, Embase and Cochrane databases. Baseline characteristics and outcomes from the included studies were extracted independently by two investigators. Either a fixed‐effects or a random‐effects model was used to composite the pooled OR for gastric cancer risk. Finally, a total of 21 studies, which comprised 402,636 participants and 4,535 gastric cancer patients, were finally included in the current meta‐analysis. Compared with those participants without IM, IM patients were at a higher risk of gastric cancer (pooled OR = 3.58, 95% CI 2.71–4.73). We observed that incomplete IM (pooled OR = 9.48, 95% CI 4.33–20.78) but not complete IM (pooled OR = 1.55, 95% CI 0.91–2.65) was significantly associated with a higher gastric cancer risk. Besides, it appeared that gastric cancer risk was higher among patients with IM in the corpus (pooled OR = 7.39, 95% CI 4.94–11.06) than those with IM in the antrum only (pooled OR = 4.06, 95% CI 2.79–5.91). And the pooled ORs for gastric noncardia cancer and gastric cardia cancer were 4.98 (95% CI 3.12–7.95) and 1.93 (95% CI 1.15–3.24), respectively. In conclusion, patients with IM were at a higher risk of gastric cancer, especially for incomplete IM and IM in the corpus. The current evidence supports the use of IM subtypes in the surveillance of gastric cancer.     

根除HP感染对胃黏膜炎症和肠腺化生的影响

目的:探讨根除幽门螺杆菌(helicobacter pylori,HP)感染对胃黏膜炎症和肠腺化生(intestinal meta-plasia,IM)的意义。方法:随访119例10年前HP感染的患者,其中62例行根除HP治疗(治疗组),57例中断治疗或仅接受对症治疗(对照组),对比其前后HP感染情况、胃黏膜炎症及肠腺化生(IM)的变化情况。结果:10年后对照组中45/57例HP呈阳性(78.94%);治疗组中15例HP呈阳性(24.19%),胃炎活动性检出率明显减少与对照组持续HP感染者比较,差异有显著性(P<0.01),肠腺化生(IM)的程度也显著减轻(P<0.05)。结论:HP感染与胃黏膜活动性炎症关系非常密切,根除HP可以减轻胃黏膜的炎症和肠腺化生(IM)程度。     

PCNA在胃粘膜肠上皮化生、异型增生和胃癌中表达及意义的研究

目的研究增殖细胞核抗原(PCNA)在胃粘膜、肠上皮化生,异型增生及胃癌中的表达.评估胃癌前病变的发展趋势,进一步探讨胃癌发生的分子生物学机制.方法应用免疫组化技术测定115例患者的PCNA表达情况.其中50例肠上皮化生、15例异型增生、50例胃癌.结果PCNA的表达从肠上皮化生、异型增生到胃癌呈递增趋势.在肠上皮化生为轻度表达,异型增生以中度表达为主,而胃癌多呈重度和过度表达.PCNA强阳性表达与胃癌分化程度,侵润深度,淋巴结转移密切相关.结论PCNA在胃粘膜不同疾病细胞核内的表达、反映了细胞增殖状态和生长速度、有助于判断肠上皮化生、异型增生的发展趋势及判断与监测胃癌的预后.     

胃镜下胃溃疡大小与溃疡边缘组织病理改变及增殖的关系

目的 通过对溃疡边缘组织病理变化及增殖细胞核抗原（PCNA）阳性表达与溃疡大小关系的研究，进一步探讨溃疡大小与癌变问题。方法 将胃窦、胃角溃疡按直径〈1cm，≥1cm为标准，将所收集的溃疡性病变分为A、B两组。SP免疫组织化学方法检测不同大小溃疡边缘PCNA阳性表达情况，HE染色观察病理改变和Hp检测。结果 胃溃疡边缘组织主要表现为CSG，CAG，IM，DYS，胃溃疡边缘组织PCNA阳性表达随着病变发展而升高；直径较大的溃疡PCNA表达较高，PCNA表达在直径≥1cm的溃疡高于直径〈1cm者（P〈0．05）。两组相比Hp检出率无显著差异。结论 各种因素造成的胃黏膜损伤使细胞增殖持续升高，而这些异常增殖导致胃溃疡恶变。PCNA表达与胃黏膜增殖恶化有关，且溃疡面积越大者恶变可能性越大。     

豫西地区胃黏膜不典型增生和肠化生的临床流行病学调查

目的：探讨近4年豫西地区胃黏膜不典型增生和肠化生的相关临床流行病学资料的特点及变化趋势。方法：选取2007年1月-2010年6月我院胃镜室行内镜检查的21932例患者为研究对象,对胃黏膜不典型增生和肠化生患者的一般临床资料和病理资料进行回顾性分析。结果：胃黏膜不典型增生和不典型增生伴肠化生有随年龄增加检出率增高的趋势,且不典型增生程度随年龄增加而程度增高。重度不典型增生≥60岁患者比例高于轻、中度不典型增生,（P〈0.05）,中度不典型增生≥60岁患者比例高于轻度不典型增生;中度肠化生≥60岁患者比例高于轻度肠化生患者（P〈0.05）。贲门部不典型增生和肠化生中≥60岁患者比例高于胃角和胃体部（P〈0.05）,幽门螺杆菌检出率均较单纯慢性浅表性胃炎组高,（P〈0.05）差异有统计学意义。结论：胃黏膜不典型增生和肠化生的发生与年龄和幽门螺杆菌感染有关,常发生于贲门部。     

Utility of subtyping intestinal metaplasia as marker of gastric cancer risk. A review of the evidence

The identification and surveillance of patients with preneoplastic lesions at high risk of progressing to gastric cancer (GC) represents the most effective way of reducing the burden of GC. The incomplete type of intestinal metaplasia (IM) could be considered as the best candidate for surveillance. However, the usefulness of subtyping of IM has been considered by some authors as limited and inconsistent. A search was carried out to identify all cross‐sectional (n=14) and follow‐up (n=10) studies that assessed the risk of GC among subjects with different types of IM. Out of the 14 cross‐sectional studies, 13 reported that the prevalence of incomplete IM was statistically significantly higher in GC than in other gastric lesions. Out of the ten follow‐up studies, six found a statistically significant association between incomplete IM and subsequent GC risk. The relative risks of GC were from 4‐ to 11‐fold higher for the presence of incomplete type in comparison to complete type or in comparison to the absence of incomplete type, among the studies that reported the magnitude of the risk. According to this comprehensive review, most of the scientific evidence supports the utility of subtyping IM as a predictor of GC risk. Recognizing its usefulness by gastroenterologists should encourage pathologists to subtype IM.     

DNA hypomethylation of proliferating cell nuclear antigen gene in human hepatocellular carcinoma is not due to cell proliferation

Proliferating cell nuclear antigen (PCNA) gene expresses preferentially in proliferative cells or tissues. The levels of PCNA mRNA are very low in livers of adult mammals. Expression of PCNA gene in hepatocellular carcinoma tissues was, however, elevated; and 5′-CCGG-3′ sequences of the gene in neoplastic tissue were less methylated. Such DNA hypomethylation was concluded, on the basis of two observations, not to be due to the cell proliferation in hepatoma tissues. First, while the expression of PCNA was increased during serum-stimulation of quiescent Hep G2 cells, the DNA methylation pattern of PCNA gene remained unchanged. Second, in rat liver regeneration, the PCNA mRNA level rose and declined, but the DNA methylation status of PCNA gene was unaltered. Therefore, the DNA hypomethylation of the PCNA gene found in hepatocellular carcinoma was not due to cell proliferation, but a possible consequence of cell transformation.