胃粘膜腺体扩张和胃腺癌细胞核DNA含量测定

采用显微分光光度计对６１例活检胃粘膜不同性质的腺体扩张和胃腺癌细胞核ＤＮＡ含量进行了检测，结果：从胃粘膜单纯性腺体扩张，异型性腺体扩张到胃腺癌，二倍体及近二倍体细胞数目逐渐减少，直至消失；增殖倍体细胞随异型增生的程序加重而递增，ＤＮＡ含量均值明显增高，并出现了一些非整体细胞，Ⅲ级异型性腺体扩张的细胞核ＤＮＡ含量，直方图与管状腺癌相接近。     

形态测量对胃粘膜异型增生及胃癌的分级与诊断研究

Measurement of cytological features and DNA content was made on epithelial cells from 40 cases of gastric dysplasia and carcinoma graded by subjective scoring with IBAS image analysis system. The measurements were statistically compared with the subjective scores by using discriminant analysis. The result was noticed to provide significant discrimination between the different groups; and nuclear area, nuclear perimeter, nuclear form factor, percentage of 2C cells and percentage of aneuploid cells were all proved to be discriminating variables. Application of classification equation derived from discriminant analysis showed good results for the prediction of different individual cases.     

中等分化肝细胞肝癌病理形态特征、PCNA和DNA指数与预后的关系

肝细胞肝癌 (ＨＣＣ)术后转移和复发率高 ,肿瘤细胞的分化是影响预后的重要原因 ,但即使同为中等分化的ＨＣＣ ,患者的生存期差异亦很大。我们收集 5 1例具随访资料的中等分化的ＨＣＣ病例 ,对其病理形态特征、ＰＣＮＡ指数、ＤＮＡ指数进行综合分析。1　材料与方法1 1　材料　上海中山医院 1989～ 1990年间病理诊断为中等分化ＨＣＣ的 5 1例手术切除标本 ,其中男性 48例 ,平均年龄 5 1 4± 11 1岁。收集其临床记录、标本的肉眼检验记录和随访资料 (包括半年 1次Ｂ超检查 ,随访截止至 1999年12月 )。用无瘤生存时间 (ｄｉｓｅａｓｅ ｆｒｅ…     

结,直肠癌细胞核DNA含量的MSP分析研究

用显微分光光度计检测64例结、直肠癌及其对照肠粘膜细胞核DNA含量,并行细胞核DNA含量分布直方图型分析。淋巴细胞和对照肠粘膜细胞核DNA含量直方图属Ⅰ型。64例结、直肠癌中,56例(87.50%)DNA直方图为Ⅱ～Ⅳ型。与对照肠粘膜细胞比较,结、直肠癌细胞核平均DNA含量、平均核面积和>2C DNA含量的细胞百分率以及各项数值的标准差均明显增加。肠癌细胞核DNA含量直方图与Dukes’分期和分化程度无关。     

肝母细胞瘤DNA含量,增殖细胞核抗原,P21及p53蛋白的表达

肝母细胞瘤ＤＮＡ含量、增殖细胞核抗原、Ｐ２１及ｐ５３蛋白的表达李代强刘磊一、材料和方法１．临床资料：收集１９８３～１９９３年３５例肝母细胞瘤标本。年龄２８天～７岁，３岁以下占８５．７％。男２１例，女１４例，男女比为１．５∶１。均以肝肿块就诊。血清ＡＦ...     

AMACR／P504S可用于区分肝细胞癌、异型增生肝细胞与良性非异型增生性肝细胞

AMACR/P504S是诊断前列腺癌的一个辅助指标,在前列腺腺癌中P504S呈胞质弥漫或顶端粗糙颗粒状染色。已有的研究表明AMACR/P504S可在多种正常组织和恶性肿瘤包括肝细胞癌中表达。为了研究AMACR/P504S在良性非异型增生肝组织、肝细胞异型增生和肝细胞癌中的不同表达,作者采用免疫组化方法检测了20例肝细胞癌及其相应的癌旁肝组织中AMACR/P504S的表达。结果发现所有20例肝细胞癌均表达AMACR/P504S,其中16例染色呈粗糙的颗粒状,4例呈细腻的斑点状和粗糙的颗粒状。17例阳性表达于肿瘤细胞基底旁,3例为基底旁和弥漫分布。在所有20例…     

两株新的抗肝细胞肝癌单克隆抗体的制备及特异性鉴定

以外科手术切除的肝癌标本制备的细胞悬液和新建株的肝癌细胞为免疫原。籍多免疫除经致敢ＢＡＬＢ／ｃ小鼠，经２０次融合，从近１０，０００个融合孔中，筛选出两株（ＨＡＢ２５，ＨＡｂ２７）肝癌单克隆抗体，在９４例肝癌１４１例其他肝病组织，２６种正常组织，１２９例各组织系统的肝外恶性肿瘤组织上做了交叉反应，除ＨＡｂ２７与毛细胆管有弱的反应外，两株抗体与肝癌细胞结合的阳性率高（８３．１５％，８５．１１％），仅与     

Immunohistochemical analysis of p53 protein overexpression in liver cell dysplasia and in hepatocellular carcinoma

We analysed p53 protein immunoreactivity in hepatocellular carcinomas (HCCs) and in liver cell dysplasia (LCD) of patients from an area in Northern China, using five anti-p53 protein antibodies recognizing different epitopes of the protein. In HCCs, the overall prevalence of p53 protein immunoreactivity was 78.3%. However, prevalence was strongly influenced by the type of antibody used, ranging from 67.5% for antibody PAb-1801 to only 10.8% for antibodies PAb-421 and DO-7. p53 protein immunoreactivity was not related to type or grade of HCC. In contrast to former reports, p53 protein staining was restricted to nuclei only when using the CM-1 antibody, whereas two other antibodies yielded both, nuclear and cytoplasmic or membrane staining, and no nuclear staining was observed with antibodies PAb-421 and DO-7, the latter two, however, demonstrating cytoplasmic and membrane staining. For LCD, three subtypes were morphologically and karyometrically defined. Nuclei of some LCD cells were p53 immunoreactive, but positivity was restricted to the small cell variant of LCD. Positivity was different for cirrhosis with or without associated HCC, amounting to 18.9% in the former and 39.4% in the latter. Interestingly, p53 protein immunoreactivity also occurred in a set of small hepatocytes not showing the typical features of LCD and therefore classified as simple regenerating liver cells.     

Liver cell dysplasia and hepatocellular carcinoma in non-A, non-B hepatitis

Liver cell dysplasia (LCD) is a premalignant cytologic change of hepatocytes that has been statistically linked to cirrhosis, hepatocellular carcinoma (HCC), and chronic liver disease related to hepatitis B virus. The relationship of LCD to non-A, non-B (NANB) hepatitis is currently unknown. We studied liver biopsy and surgical resection specimens from 36 patients with NANB hepatitis, and identified LCD in 17 (42.5%) of 40 specimens, most often associated with cirrhosis. Dysplasia was present in individual hepatocytes, in clusters, and in a distinctive "spreading" pattern of hepatocytes about central veins. Three patients had HCC with a predominant giant cell pattern, as well as LCD. These findings suggest that LCD and HCC should be included among the potential pathologic sequelae of NANB hepatitis.     

Evaluation of DNA content in gastric dysplasia and carcinoma by image cytometry

In 30 cases of gastric dysplasia and 10 cases of gastric carcinoma, DNA content was studied by IBAS image analysis system. The mean DNA level increased steadily with the advance of histologic gradation, and the highest DNA content was observed in gastric carcinoma. No case of aneuploidy was found in mild dysplasia. In moderate dysplasia, aneuploid cells were occasionally encountered. Severe dysplasia had a lower percentage (4.48%), and gastric carcinoma was characterized by a high percentage of aneuploid cells (14.54%).     

Liver cell dysplasia and hepatocellular carcinoma: a histoiogical and immunohistochemical study

Liver cell dysplasia (LCD) was found in 28 (60%) of 47 patients with hepatocellular carcinoma (HCC); 22 (79%) of them had associated liver cirrhosis. LCD was more frequently observed in posthepatitic cirrhosis (82%) than in the other forms. Carcinoembryonic antigen (CEA), alpha-1-antitrypsin (AAT) and alpha-fetoprotein (AFP), as demonstrated by the peroxidase-antiperoxidase method, were similarly expressed both in normal and in dysplastic cells. Hepatitis B surface antigen was found in eight cases (17%), six of which were associated with LCD. HBsAg was rarely found in dysplastic cells and frequently displayed a peculiar perinuclear pattern. The possible preneoplastic role of LCD is stressed.     

Apoptosis in human hepatocellular carcinoma and in liver cell dysplasia is correlated with p53 protein immunoreactivity.

AIMS: To investigate the prevalence of apoptosis in human hepatocellular carcinomas (HCC) of different types and grades and in liver cell dysplasia, and to test whether the apoptotic rate is correlated with the p53 protein status. METHODS: 37 HCC and 66 six liver samples with liver cell dysplasia were analysed for apoptosis using in situ DNA end labelling (ISEL), and for p53 protein expression by immunohistochemistry. In HCCs, proliferative activity was quantitatively assessed using proliferating cell nuclear antigen labelling. RESULTS: The apoptotic index in HCC as based on ISEL ranged from 0.1 to 13.5 per 1000 cells analysed and was not related to type or grade. No nuclear staining was observed in multinuclear tumour cells. There was a significant correlation between the apoptotic rate and both the proliferative activity and p53 protein reactivity. In liver samples containing p53 protein positive liver cell dysplasia cells, there was a significantly higher apoptotic rate of these cells. CONCLUSIONS: Apoptosis is detectable in HCC, and is not related to type and grade. There is a highly significant positive correlation between the apoptotic rate in HCC and both the proliferative activity and p53 protein expression. A similar phenomenon occurs for putative cancer precursors. The findings support the role of p53 in regulating apoptosis in preneoplastic and neoplastic liver lesions.     

Analysis of the precore and core promoter DNA sequence in liver tissues from patients with hepatocellular carcinoma.

To investigate the role of mutant hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC), 20 patients with HCC were studied for precore and core promoter mutations in tumorous and nontumorous tissues. The precore and core promoter region was amplified and analyzed by direct sequencing. Among the 20 tumorous and nontumorous tissues, precore mutant HBV was found in 12 (60%) and 18 (90%), respectively. Of the 12 tumorous tissues with precore mutant, nine tissues had a single mutation (1896) and one tissue had another single mutation (1899). The remaining two tissues had a double mutation (1896 and 1899). A single mutation (1896) and a single mutation (1899) were found in 11 and two of the 18 nontumorous tissues with precore mutant, respectively. Among 20 tumorous and nontumorous tissues, HBV with a C to T mutation at nucleotide (nt) 1846 was detected in six and eight, respectively, and was associated with the virus carrying a mutation (1896 or 1899) except in two tumorous tissues. Mutations at nt 1762 and 1764 in core promoter were observed in 16 (80%) tumorous tissues and 18 (90%) nontumorous tissues. Mutations in the precore and core promoter region were found frequently in nontumorous tissue and in tumorous tissue (18/20 and 12/20 in precore region, 18/20 and 16/20 in core promoter respectively). The high prevalence of precore and core promoter mutations in liver tissue from patients with HCC suggests that these mutations may contribute to the development of HCC.     

Predictive value of liver cell dysplasia for development of hepatocellular carcinoma in patients with non-cirrhotic and cirrhotic chronic viral hepatitis

AIMS: Hepatocellular carcinoma (HCC) frequently develops in patients with chronic viral hepatitis, especially in the cirrhotic stage. We retrospectively studied whether the presence of the putative preneoplastic lesions large liver cell dysplasia (LLCD) and/or small liver cell dysplasia (SLCD) in a needle liver biopsy of these patients are a risk factor for the development of HCC. Methods and results: The presence of LLCD and SLCD in the needle liver biopsy taken at the initial work-up of 115 patients with chronic hepatitis B or C was assessed retrospectively. LLCD and SLCD were present in the initial biopsy of, respectively, 35 (30%) and 25 patients (22%). During a mean follow-up of 107 months, 16 patients (14%) developed HCC and this occurred significantly more frequently in patients with cirrhosis, age > or = 55 years, LLCD or SLCD. Cirrhosis and LLCD were independent risk factors for HCC development. CONCLUSIONS: Our findings indicate that the presence of LLCD in a needle liver biopsy of patients with viral-induced chronic liver disease is an independent risk factor for the development of HCC. If these results are confirmed, the presence of LLCD can be used to identify a subgroup of patients at high risk for HCC requiring more intensive screening.     

宫颈癌及癌前病变应用HPV-DNA亚型检测联合液基细胞学检测的准确性

目的测定宫颈癌（Cc）癌组织和非癌组织的HPVcccDNA含量,并联合联合液基细胞学进行检测,探讨癌组织HPVcccDNA与cc的关系。方法采用荧光定量PCR检测45例宫颈癌患者癌组织和非癌组织中总HPVDNA和HPVcccDNA含量,分析2种组织中HPVcccDNA和总HPVDNA与癌组织病理分级的关系。结果血清HBsAg阳性的癌组织较对应非癌组织总HPVDNA无显著性差异（4.33士1.1μS,4.13±1.09,P=0.439）,而癌组织HPVcccDNA水平显著升高（3.09士1.22μS 2.62士0.97,P=0.039）,HPVcccDNA所占比例也显著升高（70.09％μS 62.33％,P=0.015）;42例中有14例（33％）的癌组织HPVcccDNA几乎成为HPVDNA唯一存在形式;3例血清HBsAg阴性的cc中均检测到了HPVcccDNA的存在,且HPVcccDNA比例均较高;癌组织和非癌组织HPVcccDNA与组织总HPVDNA均呈正相关（r=0.8244,P〈0.001;r=0.8460,P〈0.001）：癌组织中HPVcccDNA定量和肿瘤的病理分级无明显相关性（P〉O．05）。结论宫颈癌组织中HPVcccDNA水平和所占比例较非癌组织均升高,HPVcccDNA在宫颈癌变中有重要的作用,但水平与宫颈癌的病理分级无明显相关。     

Frequent integration of hepatitis B virus DNA in noncancerous liver tissue from hepatocellular carcinoma patients

To investigate the relationship between hepatocarcinogenesis and integration of hepatitis B virus (HBV) DNA in the cellular DNA of the liver, we studied the integration of HBV DNA in various noncancerous regions of the liver from 31 patients using Southern blot analysis. Of 13 patients without hepatocellular carcinoma (HCC), 4 had heterogeneously integrated HBV DNA. Of the latter four patients, two had chronic liver disease, and two had nonspecific histological changes. In contrast, integration of HBV DNA was found in noncancerous tissue from 11 of 18 patients with HCC. In eight patients, homogeneous integration was found in noncancerous tissue, and restriction fragments of integrated HBV DNA were different from those found in cancerous tissue. Moreover, integration of HBV DNA was found in all portions examined from the same liver, and homogeneously integrated HBV DNA showed different restriction patterns in different areas. These results suggest that integration of HBV DNA may occur in heterogeneous sites of cellular DNA before hepatocarcinogenesis. Subsequently, multi-focal clonal populations develop from these hepatocytes, especially frequently in the case of HCC. Integrated HBV DNA may play an important role in the clonal growth of hepatocytes, although the development of HCC requires additional factors.