食管和贲门癌原发病灶和淋巴结转移灶p53蛋白聚集变…

目的：通过对食管和贲门癌原发病灶和淋巴结转移病灶肿瘤抑制基因ｐ５３变化规律的研究，加深对食管和贲门癌转移发生的分子学基础的了解。方法：采用组织病理学和免疫组织化学（ＡＢＣ）方法，对３１例手术切除的食管和贲门癌原发病灶和转移病灶肿瘤抑制基因ｐ５３蛋白聚集进行比较研究。结果：３１例手术标本中，病理检查发现２４例食管鳞状细胞癌，７例为贲门腺癌。研究表明：２４例食管原发和转移鳞癌中，１１例原发和转移病灶中     

免疫组化和PCR—SSCP检测p53基因异常的一致性探讨

目的：探讨免疫组化检测ｐ５３蛋白表达和ＰＣＲ－ＳＳＣＰ检测ｐ５３基因突变的一致性。方法：单克隆抗体ＤＯ－７检测８５例非小细胞肺癌（ＮＳＣＬＣ）的ｐ５３蛋白表达，ＰＣＲ－ＳＳＣＰ检测其中３１例腺癌的ｐ５３基因突变。结果：８５例ＮＳＣＬＣ中ｐ５３蛋白表达阳性率为６８％（５８／８５），３１例腺癌中ｐ５３蛋白表达阳性率为６１％（１９／３１），１４例（４６％）出现ｐ５３基因５～８外显子突变，ｐ５３蛋白免疫组化和ＰＣＲ－ＳＳＣＰ检测ｐ５３基因突变无显著相关（χ２＝０．１，Ｐ＝０．７６），其一致率为５２％。结论：ｐ５３蛋白表达并不能很好地反映ｐ５３基因突变。     

大肠肿瘤p53基因表达及其临床病理意义

应用免疫组织化学Ｓ－Ｐ法检测了１０６例良，恶性大肠组织中抑癌基因ｐ５３基因表达民政部结果发现；正常大肠粘膜及非肿瘤性息肉均阴性；腺癌中１８．１８％ｐ５３阳性，但均为弱阳性，局灶型，而腺癌组织中４２．１１ｐ５３阳性，其中７５％为强阳性或阳性；癌组织中ｐ５３阳性表达与大肠癌的分化、组织学类型、侵范围是淋巴结转移等因素有关，低分化腺癌及粘液癌阳性率较高，ｐ５３阳性及强阳性者更易于侵出肌层及发生淋巴结转移     

p53和nm23联合表达对食管鳞癌淋巴结转移的影响

目的：探讨ｐ５３ 和ｎｍ２３ 表达作为食管鳞癌转移标志物的实用价值。方法：采用免疫组化方法检测８５ 例原发性食管鳞癌中ｐ５３ 和ｎｍ２３ 蛋白表达。结果：６３－５３ ％ （５４／８５） 肿瘤呈ｐ５３ 阳性表达,ｐ５３ 阳性表达与肿瘤淋巴结转移和ＴＮＭ 分期有关（Ｐ值均为０－００１）。４０ ％（３４／８５） 肿瘤为ｎｍ２３ 低表达。ｎｍ２３ 低表达与肿瘤浸润深度、淋巴结转移、ＴＮＭ 分期有关（ Ｐ值分别为０－０３２、０－００１、０－００１） 。单因素分析显示：ｐ５３ 和ｎｍ２３ 表达为影响淋巴结转移的主要因素（ ＯＲ值分别为６－９８４ 和０－０８７,Ｐ＜０－００１）。多因素分析显示：ｎｍ２３ 表达是影响淋巴结转移的一个独立因素（珘ｂ＝ － ０－８４８１ , ＯＲ＝ ０－１８１, Ｐ＝ ０－０００１） 。ｐ５３阳性肿瘤具有高度淋巴结转移的倾向（珘ｂ＝ ０－３１５０, ＯＲ＝２－２８４,Ｐ＝ ０－０５６５）,其它临床病理学参数与淋巴结转移之间未见明显关系（Ｐ＞ ０－０５） 。ｐ５３ 和ｎｍ２３ 异常表达之间呈负相关（ｒｓ＝ － ０－３８４９ ,Ｐ＝ ０－０００３）,在促进肿瘤的进展和转移过程中起联合作用。结论：ｐ５３ 和ｎｍ２３ 联合表达对判断食管鳞癌患者     

甲状腺乳头腺瘤中EGFR,nm—23—H1和p53蛋白的表达

目的：探讨ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白在甲状腺乳头状腺癌中的表达及其与淋巴结转移的关系。方法：应用免疫组化ＡＢＣ法检测３６例有颈淋巴结转移的甲状腺乳头状腺瘤的原发灶与转移灶和４０例无转移的甲状腺乳头状腺癌中ＥＧＦＲ、ｎｍ２３－Ｈ１和ｐ５３蛋白的表达。结果：７６例甲状腺乳头状腺癌的ＥＧＦＲ、ｎｍ２３－Ｈ１及ｐ５３蛋白的阳性表达率分别为５５．３％、６０．５％和１１．８％；但有转移的甲状腺乳头状     

p53基因蛋白异常表达在胃癌中的意义

目的：探讨ｐ５３基因表达异常的意义。方法：用免疫组织化学方法研究ｐ基因蛋白在胃癌中的表达。结果：７２例胃腺癌中３６例阳性，高分化腺癌和低分化腺癌Ｐ５３阳性率明显高于粘液，不同浸润深度的癌细胞与癌细胞Ｐ５３阳性程度有关，在淋巴结转移组和无转移组间Ｐ５３阳性率和阳性程度均无程度差异。病人的生存时间与Ｐ５３阳性我明显的相关性，癌旁肠上皮化生和异型增生腺体全部为阴性。结论．Ｐ５３异常 表达是细胞癌变的标志     

垂体腺瘤p53蛋白表达及其意义

目的：研究突变型ｐ５３癌基因在垂体腺瘤中的表达。方法：应用免疫组化ＡＢＣ法检测６４例垂体腺瘤（复发组３１例，非复发组３３例），６例正常垂体、２例垂体瘤中ｐ５３蛋白表达阳性，非复发组中有２例ｐ５３蛋白表达阳性，两组差异有显著性。２例垂体癌ｐ５３蛋白强阳性表达，６例正常垂体无阳性表达。ｐ５３蛋白在不同激素类型垂体腺癌中的阳性表达率差异无显著性。结论：ｐ５３蛋白高表达与少数垂体腺癌在潜在恶性及复发有关，     

大肠腺癌p53基因cDNA突变与突变型p53基因蛋白表达的相互关系和意义

目的：探讨大肠腺癌突变型ｐ５３基因蛋白表达与ｐ５３基因ｃＤＮＡ突变间的相互关系和意义。方法：对１００例新鲜大肠腺癌组织采用ＰＡｂ２４０单克隆抗体免疫组织化学染色（ＬＳＡＢ法）检测突变型ｐ５３基因蛋白表达、ＲＴ－ＰＣＲ－ＳＳＣＰ检测ｐ５３基因ｃＤＮＡ突变，并比较它们间相互关系。结果：１００例大肠腺癌中，７６例ＰＡｂ２４０单抗阳性（７６％），５１例ｐ５３基因ｃＤＮＡ突变阳性（５１％）；ＰＡｂ２４０单抗反应与ｐ５３基因ｃＤＮＡ突变比较，两者皆阳性４９％，两者中一者阳性２９％，两者皆阴性２２％（Ｐ＜０．０００１）。结论：ｐ５３基因ｃＤＮＡ突变与其基因蛋白产物结构改变高度吻合，大肠腺癌ｐ５３基因ｍＲＮＡ（ｃＤＮＡ）突变是参与和影响突变型ｐ５３基因蛋白结构改变和生物学行为的主要因素     

p53过表达与胃癌患者淋巴结转移的关系

应用Ｓ－Ｐ免疫组化方法，研究ｐ~（５３）在８８例原发性胃癌患者的表达变化与肿瘤细胞增殖和浸润深度及淋巴结转移的关系。发现ｐ~（５３）阳性染色率为４８．９％，ｐ~（５３）阳性染色与肿瘤浸润深度及癌细胞增殖活性呈正相关，ｐ~（５３）阳性肿瘤的淋巴结转移率（９３％）明显高于ｐ~（５３）阴性的肿瘤（６０％，Ｐ＜０．０５）。提示ｐ~（５３）过表达在胃癌淋巴结转移和肿瘤浸润及增殖中起重要作用。     

p53、p16、nm23基因蛋白在肺癌中的表达及意义

目的：研究肺癌组织中ｐ５３,ｐ１６,ｎｍ２３基因蛋白的表达：方法：应用免疫组化ＬＳＡＢ方法检测１２９例肺癌标本中;ｐ５３,ｐ１６,ｎｍ２３基因蛋白的表达。结果：ｐ５３,ｐ１６,ｎｍ２３蛋白在肺癌中的阳性表达率分别为５２．７％,４５．７％,５５．８％;３种蛋白阳性表达率与组织学分型无明显相关;肺腺癌淋巴结转移阳性组ｐ５３蛋白阳性表达率显著高于淋巴结无转移组;     

Mutated p53 as a molecular marker for the diagnosis of head and neck cancer

In total, 10-30% of patients with head and neck squamous cell carcinoma (HNSCC) develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC): small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies, p53 mutations have been considered as selective and sensitive DNA markers of cancer cells. There are two potential problems in using mutated-p53 DNA as a marker. Firstly, p53 mutations occur early in progression and might therefore detect unresected precursor lesions besides tumour cells. Secondly, DNA is a very stable biomolecule that might lead to false-positive results. These two potential problems have been evaluated in this study. Fifty patients with a radical tumour resection were included, of whom 30 showed a p53 mutation in the primary tumour. Histopathologically tumour-free surgical margins were quantitatively analysed for mutated p53 by molecular diagnosis (plaque assay) and subsequent (immuno)histopathology. p53 mutated DNA was detected in the surgical margins of 19/30 patients. Immunohistochemistry confirmed the presence of small tumour foci in 2/19 mutated p53-positive cases. In 7/19 cases, the tumour-specific p53 mutation was found in unresected dysplastic mucosal precursor lesions. Moreover, in a number of cases small p53-immunostained patches were detected, but the mutations found were never tumour-related. By screening contralateral exfoliated cells and plaque assays on RNA it was shown that detection of mutated-p53 DNA is prone to false-positive results. In conclusion, using p53 mutations as a marker, both MRC and unresected mutated p53-positive mucosal precursor lesions are detected within surgical margins. Molecular assessment of surgical margins using p53 mutations enables the selection of HNSCC patients at high risk for tumour recurrence, but tumour RNA seems at present to be a more specific biomolecule for analysis than tumour DNA.     

Epstein-Barr virus-positive multiple early gastric cancers and dysplastic lesions: A case report

Epstein-Barr vlrus (EBV) has been implicated as a causal virus of gastrlc cancer with episomal monoclonality, elevated antibodles and a unlque morphologlc expression in the early intramucosal stage, but the infection mechanisms have not been demonstrated. EBV has been shown only in the cancerous lesions by the highly sensltlve EBVencoded small RNA in situ hybridization (EBER-ISH) method, not in the dysplastic mucosa adjacent to the cancer. A case is presented of multiple EBV-positive gastric cancer and dysplastic epithelium observed In a 52-year-old man. Serlai cut sections of the gastrectomy specimen showed four small cancerous lesions, three of which were EBER-posltlve, and three EBER-positive, minute, non-cancerous dysplastic lesions. The three cancerous lesions were intramucosal cancer, with one having minimal submucosal invasion forming 8 lymphoeplthelioma-like histology. All of these EBER-posltlve cancerous and dysplastic lesions showed Intense CD8T-lyrnphocytic Infiltration. There was no such findings in the EBV-negative cancerous lesion. It was concluded that EBV infection may occur in the epitheilal cells of atrophic gastric mucosa, and progress to cancer with monoclonal expansion through the EBV-positive dysplastic change. Cytotoxlc T-lymphocytic reactions can occur even in the dysplastic lesions. Multifocal EBV infection in the gastric mucosa may occur and, if necessary, total gastrectomy Is recommended in such a case.     

Long-term effects of levonorgestrel-releasing intrauterine system on tamoxifen-treated breast cancer patients: a meta-analysis

Objective: The aim of the study is to assess the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) on the tamoxifen-induced endometrial lesions in breast cancer patients. Methods: PubMed and EMBASE databases were searched for eligible studies. Odds ratios were obtained to estimate the association between the LNG-IUS and tamoxifen-induced endometrial lesions. The fixed effects or random-effects model was used to combine data depending on heterogeneity. Results: With three eligible randomized clinical trials involving 359 patients, this analysis demonstrated tamoxifen-treated breast cancer patients using the LNG-IUS derived benefit from de novo polyps prevention (P < 0.0001, OR 0.18, 95% CI: 0.08-0.42). However, the LNG-IUS only showed a trend of maintaining endometrial proliferation or secretory status (P = 0.05, OR 0.36, 95% CI 0.13-1.02) and no statistical difference in atrophic or inactive changes (P = 0.13, OR 0.24, 95% CI 0.04-1.53) or endometrial hyperplasia without atypia (P = 0.08, OR 0.20, 95% CI 0.04-1.18). The LNG-IUS didn’t have an increased incidence in breast cancer recurrence (P = 0.28, OR 1.75, 95% CI: 0.64-4.80) and cancer-induced death (P = 0.71, OR 1.22, 95% CI: 0.42-3.52). Bleeding in the treatment group was statistically more frequent than that in the control group (OR 6.20, 95% CI: 2.99-12.85, P < 0.00001). Conclusions: This analysis verifies the efficacy of the LNG-IUS in preventing tamoxifen-induced polyps. The LNG-IUS didn’t have an increased incidence in breast cancer recurrence and cancer-induced death. Long-term, large randomized studies of the LNG-IUS will be necessary to determine the benefit and risk in tamoxifen-treated breast cancer patients.     

Histology of aberrant crypt foci in the human colon

Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5–10 min. The strips were measured, put on a glass slide and observed under a light microscope at ×25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.     

应用内镜黏膜下剥离术处理食管黏膜病变疗效评价

目的应用内镜黏膜下剥离术(ESD)处理食管早癌及癌前病变,评价其疗效和安全性。方法回顾性分析2008年10月至2009年10月分别于复旦大学附属中山医院和新疆医科大学第六附属医院内镜检查及病理诊断为早期食管癌及癌前病变35例患者,其中男性24例,女性11例;年龄38～78岁,平均年龄60岁。对患者行内镜下治疗,观察术中出血、穿孔及术后食管狭窄的发生情况,统计病灶完整大块切除率与组织学完全切除率,通过随访评价复发或转移情况,对内镜治疗短期效果进行初步评价。结果完成ESD操作28例,7例(20.0%)改为内镜下黏膜切除术(EMR)切除,手术耗时20～125min,平均耗时65 min。颈部气肿1例,术中穿孔2例(5.7%),术中少量出血8例(22.9%),术后延迟性出血1例。组织学治愈26例(74.3%)。除2例手术治疗外,32例完成随访,1例(3.3%)失访。随访4～26个月,中位随访时间10个月。随访中,3例复发,复发率9.4%(3/32),3例发生术后食管狭窄包括1例复发病例。结论 ESD治疗早期食管癌及癌前病变具有较好的疗效和安全性。     

醋酸-靛胭脂染色在基层医院早期胃癌及癌前病变诊断中的应用

目的探讨提高基层医院早期胃癌及癌前病变检出率的方法。方法经胃镜检查发现胃黏膜异常进行醋酸-靛胭脂染色后取活检病理检查患者72例为染色组,同期胃镜下发现黏膜异常患者直接取组织活检病理检查患者68例为对照组,观察胃黏膜染色情况并与病理检查结果对比分析,比较2组患者早期胃癌及癌前病变的检出率。结果醋酸-靛胭脂染色后胃黏膜表现为黏膜褪色(16.7%)、着色不良(63.9%)及着色均匀(14.3%)。其中染色组黏膜褪色患者中早期胃癌或高级别上皮内瘤变的检出率(91.7%)显著高于着色不良(8.6%)和着色均匀(0.0%);黏膜着色不良中低级别上皮内瘤变或肠上皮化生比例(82.6%)显著高于黏膜褪色(8.3%)和着色均匀(14.3%)。染色组早期胃癌及癌前病变检出率(13.9%,63.9%)均分别显著高于对照组(2.9%,29.4%)。结论胃镜下醋酸-靛胭脂染色能够提高基层医院早期胃癌及癌前病变的检出率,并且成本低廉,操作简便,适宜于基层医院推广应用。     

长链非编码RNA与口腔癌研究进展

口腔癌(oral cancer)是口腔外科常见的恶性肿瘤,易发生转移且预后不容乐观,长链非编码RNA(Long non-coding RNA,lncRNA)是一类内源性的长度大于200个核苷酸、缺少特异完整的开放阅读框,不具有蛋白质编码功能的转录本,最初认为并没有生物学功能,但随着生物学技术的发展,发现其能够在表观遗传水平、转录水平和转录后水平等多个层面上调控基因的表达,从而影响机体生长、发育、衰老和死亡等重要的生命活动以及疾病的发生和发展。近年来的研究显示口腔癌的发生、发展、侵袭、转移和预后与lncRNA的表达水平密切相关。因此本文对lncRNA在口腔癌中的研究进展进行论述,并探讨lncRNA与口腔癌发生、发展之间的关系,旨在进一步阐述lncRNA与OSCC的关系并为寻找口腔癌肿瘤标志物提供新的方向,为口腔癌患者提供新的治疗策略。     

MuDeRN: Multi-category classification of breast histopathological image using deep residual networks

MotivationIdentifying carcinoma subtype can help to select appropriate treatment options and determining the subtype of benign lesions can be beneficial to estimate the patients’ risk of developing cancer in the future. Pathologists’ assessment of lesion subtypes is considered as the gold standard, however, sometimes strong disagreements among pathologists for distinction among lesion subtypes have been previously reported in the literature.ObjectiveTo propose a framework for classifying hematoxylin-eosin stained breast digital slides either as benign or cancer, and then categorizing cancer and benign cases into four different subtypes each.Materials and methodsWe used data from a publicly available database (BreakHis) of 81 patients where each patient had images at four magnification factors (×40, ×100, ×200, and ×400) available, for a total of 7786 images. The proposed framework, called MuDeRN (MUlti-category classification of breast histopathological image using DEep Residual Networks) consisted of two stages. In the first stage, for each magnification factor, a deep residual network (ResNet) with 152 layers has been trained for classifying patches from the images as benign or malignant. In the next stage, the images classified as malignant were subdivided into four cancer subcategories and those categorized as benign were classified into four subtypes. Finally, the diagnosis for each patient was made by combining outputs of ResNets’ processed images in different magnification factors using a meta-decision tree.ResultsFor the malignant/benign classification of images, MuDeRN’s first stage achieved correct classification rates (CCR) of 98.52%, 97.90%, 98.33%, and 97.66% in ×40, ×100, ×200, and ×400 magnification factors respectively. For eight-class categorization of images based on the output of MuDeRN’s both stages, CCRs in four magnification factors were 95.40%, 94.90%, 95.70%, and 94.60%. Finally, for making patient-level diagnosis, MuDeRN achieved a CCR of 96.25% for eight-class categorization.ConclusionsMuDeRN can be helpful in the categorization of breast lesions.