胰腺癌及其癌旁组织p21与p53蛋白的表达

了解胰腺癌旁组织ｐ２１与ｐ５３蛋白的表达与胰腺癌多中心性的机制。方法；采用免疫组化法４２例胰腺异常癌，相应的２７例胰腺癌旁组织和对照的１２例正常胰腺组织石蜡包埋标本进行了ｐ２１和ｐ５３蛋白阳性染色分别为２４例。２７例癌旁组织呈阳性染色则分别为１３例和１１例，染色细胞呈灶性分布，其相应的癌组织也为阳性。     

p53和p21基因蛋白表达与胃癌侵袭力的关系

采用免疫组织化学方法研究了６８例胃癌中癌细胞ｐ５３和ｐ２１基因蛋白表达与癌细胞侵袭力的关系。结果表明：６８例胃癌中有３６例ｐ５３基因蛋白染色阳性（５２．９％）,４８例ｐ２１基因蛋白染色阳性（７０．６％）;浸润于浆膜层和肌层的癌细胞ｐ５３蛋白染色的阳性程度明显高于粘膜层癌细胞（Ｐ＜０．０５）;浸润性生长的癌细胞中ｐ５３和ｐ２１蛋白阳性程度均明显强于膨胀性生长的癌细胞（Ｐ＜０．０５）;淋巴结转移病例的癌细胞其ｐ５３和ｐ２１蛋白染色阳性率（分别为５４．３％和７３．９％）与无淋巴结转移的病例（分别为５０．０％和６３．６％）无显著性差异（Ｐ＞０．０５）;有淋巴结转移的病例中,原发癌ｐ５３蛋白阳性强度与转移癌正相关（γ＝０．６８,Ｐ＜０．０１）。结果提示：ｐ５３和ｐ２１基因蛋白染色阳性程度较高的胃癌细胞具有较强的侵袭力。     

p53蛋白和MDM 2蛋白在食管鳞状细胞癌中的表达及意义

为了探讨肿瘤抑制基因ｐ５３和癌基因ＭＤＭ２在食管鳞状细胞癌中的表达及其意义，采用免疫组织化学链菌素亲生物素蛋白过氧化物酶连接法（ＳＰ法），检测了６８例食管鳞状细胞癌中ｐ５３蛋白和ＭＤＭ２蛋白的表达，结果显示ｐ５３蛋白和ＭＤＭ２蛋白阳性率分别为６０．３％（４１／６８）和４２．６％（２９／６８），ｐ５３蛋白阳性率与食管鳞状细胞癌分级呈显著正相关（Ｐ＜０．０１），ＭＤＭ２蛋白阳性率与食管鳞状细胞癌分级呈显著负相关（Ｐ＜０．０１），并与食管鳞状细胞癌临床病理分期呈显著负相关（Ｐ＜０．０５）。在６８例食管鳞状细胞癌中，ｐ５３蛋白阳性表达者４１例，其中ｐ５３蛋白和ＭＤＭ２蛋白表达均阳性者１２例，ＭＤＭ２蛋白表达阴性者２９例；在６８例食管癌中，ＭＤＭ２蛋白阳性表达者２９例，其中ＭＤＭ２与ｐ５３蛋白均阳性者１２例，ｐ５３蛋白表达阴性者１７例，两者呈显著负相关（Ｐ＜０．０１），ｐ５３蛋白和ＭＤＭ２蛋白表达均阴性者１０例。可以认为ｐ５３蛋白和ＭＤＭ２蛋白表达可作为食管鳞状细胞癌病理分级参考指标之一，ＭＤＭ２蛋白表达还可作为食管鳞状细胞癌临床病理分期的参考指标之一，并间接证明ＭＤＭ２蛋白对ｐ５３蛋白表达具有负性调节作用。     

大肠癌旁粘膜细胞增殖模式与术后复发机制的探讨

目的：探讨大肠癌旁粘膜细胞增殖模式变化与肿瘤术后复发的关系。方法：用免疫组化染色方法对７８例大肠癌标本的癌组织、癌旁粘膜及１２例正常大肠粘膜进行ｐ５３蛋白、增殖细胞核抗原（ＰＣＮＡ）检测,并进行随访。结果：癌组织ＰＣＮＡ高表达明显高于癌旁（Ｐ＜００１）,癌旁ＰＣＮＡ高表达与隐窝增殖区扩大、上移,明显影响术后第１年局部复发死亡率（Ｐ＜００１）,癌组织ｐ５３蛋白阳性表达率６１５４％,癌旁为２６９２％,癌及癌旁ｐ５３阳性表达不影响细胞增殖活性及术后第一年内的复发死亡率（Ｐ＞００５）。结论：大肠癌的复发可能与大肠癌的发生一样是正常隐窝增殖分化失调的顺序过程。ＰＣＮＡ可直观表现其增殖活性及增殖模式。ｐ５３突变及表达是多中心性的,癌旁ｐ５３突变点的存在是肠癌局部复发的潜在因素。     

食管鳞状细胞癌p53蛋白的免疫组化研究

应用ｐ５３单克隆抗体对６４例食管鳞癌病例进行了ＡＢＣ免疫组化染色，结果发现阳性染色物质核浆中均存在。６４例鳞癌标本在肿瘤区，癌旁组织以及“正常区”组织中的ｐ５３蛋白阳性率分别为６４．１％（４１／６４），２０．３％（１３／６４）和４．７％（３／６４），按病理Ⅰ、Ⅱ、Ⅲ分级分类，其阳性率分别为４１．７％，６１．１％和９０．９％，三级标本比较，ｐ５３蛋白表达有显著差异（Ｐ〈０．０１）。按淋巴结转移和未转     

p16蛋白在大肠癌中的表达及其临床意义

应用免疫组化ＬＳＡＢ法检测了１０５例大肠癌组织中ｐ１６蛋白。结果：大肠癌ｐ１６蛋白表达阳性率为６０．０％，与癌组织分化程度呈正相关（Ｐ＜０．０１），与癌组织浸润深度和Ｄｕｋｅｓ′分期呈负相关（Ｐ＜０．０１）。无区域淋巴结转移者的ｐ１６蛋白表达阳性率为７６．９％，伴区域淋巴结或远处器官转移者为５０．０％，二者有显著性差异（Ｐ＜０．０１）。生存超过５年者ｐ１６蛋白表达阳性率（８３．３％）明显高于５年内死亡者（５３．１％），有显著性差异（Ｐ＜０．０５）。说明ｐ１６基因能抑制大肠癌的浸润与转移，ｐ１６蛋白表达水平可作为判断大肠癌患者预后的生物学指标     

胰腺癌及其癌旁组织p21与p53蛋白的表达

目的：了解胰腺癌旁组织p21与p53蛋白的表达与胰腺癌多中心性的机制。方法：采用免疫组化法对42例胰腺导管怎、相应的27例胰腺癌分组织和对照的12例正常胰腺组织石蜡包理标本进行p21和p53蛋白单抗的免疫级化染色。结果：42例胰腺癌组织中呈p21和p53蛋白阳性染色分别为24例（67％）和20例（48％）。27例癌分组织呈阳性染色则分别为13例（48％）和11例（41％），染色细胞呈灶性分布．其相应的癌组织也为阳性。对照组12例正常胰腺组织呈p21阳性染色仅1例，而无1例呈p53阳性染色，与胰腺癌和癌旁组织p21或p53阳性车间均有显著差异（P＜0.01）。结论：胰腺癌分组织中某些细胞呈p21或p53阳性染色，这些细胞可能较易发生癌变，使胰腺癌呈多中心性发生。     

Bax在肝癌和癌旁组织中的表达及与突变型p53蛋白表达的关系

目的探讨凋亡基因ｂａｘ和ｐ５３与肝癌发生的关系。方法应用免疫组织化学方法检测３４例肝细胞癌和癌旁组织中ｂａｘ和ｐ５３的表达。结果肝癌组织中ｂａｘ阳性７例，ｐ５３阳性２０例，癌旁组织中分别为２２例和６例。ｐ５３表达与组织学分级有明显关系（Ｐ＜０．０５），而ｂａｘ与组织学分级无关（Ｐ＞０．０５）。结论ｂａｘ和ｐ５３蛋白可能与肝癌发生有关，但作用途径可能不同。     

肝癌及癌旁组织p21蛋白表达与其病理学指征的相关性

目的：研究肝细胞癌（ｈｅｐａｔｏｃｅｌｌｕｌａｒ ｃａｒｃｉｎｏｍａ,ＨＣＣ）及癌旁组织ｐ２１蛋白表达的意义。方法：应用免疫组化方法结合计算机图像分析技术测定４７例肝癌手术标本ｐ２１蛋白的表达水平。并与临床病理学指标进行对比。结果：癌旁组织ｐ２１蛋白表达阳性率及表达水平均高于癌组织（Ｐ〈０．０１）,癌旁组织ｐ２１蛋白表达水平在侵袭转移性ＨＣＣ高于非侵袭无转移性ＨＣＣ（Ｐ〈０．０１）。并且癌旁组织ｐ     

肺癌p53蛋白和增殖细胞核抗原的检测及其意义

目的：探讨ｐ５３蛋白、ＰＣＮＡ联合表达在临床中的意义。方法应用免疫组织化学Ｓ－Ｐ法检测１０１例肺癌中ｐ５３蛋白、ＰＣＮＡ的表达。结果ｐ５３蛋白在肺癌组织中有较高的表达。总阳性率为５９．４％（６０／１０１）。Ｐ５３蛋白表达与肿瘤分化程度呈正相关（Ｐ〈０．０５）。而与肺癌患者的生存期呈负相关（Ｐ〈０．０１）。Ｐ５３蛋白表达与ＰＣＮＡ染色密切相关（Ｐ〈０．０５）。结论Ｐ５３蛋白表达可作为判断肺癌患者预后     

喉粘膜上皮异型增生p53、H-ras过度表达与预后的关系

目的：探讨喉粘膜上皮异型增生ｐ５３、Ｈ－ｒａｓ过度表达与预后的关系。方法：应用免疫组化ＡＢＣ法对６３例喉粘膜上皮异型增生（经随访其中４０例恶变为癌），５６例喉鳞癌和７例喉正常组织进行检测。结果：ｐ５３蛋白阳性率在喉粘膜上皮异型增生恶变组为５０．０％，未恶变组为１７．４％，喉癌组为５１．８％，正常组织无表达。恶为组与未恶变组间，未恶变组与喉癌组间的Ｐ５３蛋白表达差异有统计学意义（分别为Ｐ〈０．０５和     

Human pancreatic ribonuclease 1: expression and distribution in pancreatic adenocarcinoma

BACKGROUND: Human pancreatic ribonuclease (RNase 1) is a pancreatic enzyme that is present at high levels in the serum of most patients with pancreatic adenocarcinoma. For this reason, the authors studied its patterns of expression at the single-cell level in pancreatic adenocarcinoma tissues by immunohistochemical analysis and in situ hybridization (ISH). METHODS: Immunohistochemical analysis with polyclonal antibodies against RNase 1 and by ISH with digoxigenin-labeled RNase 1 probe were used to detect RNase 1 in the neoplastic cells of ductal type pancreatic adenocarcinomas. RESULTS: Fifteen of 18 carcinoma samples were positive for RNase 1, demonstrating that the expression of ribonuclease that the authors observed previously in human pancreatic adenocarcinoma cell lines was not an artifact of cell culture. The authors also found RNase 1 in some of the metaplastic ducts and atrophic islets in 4 of 6 chronic pancreatitis samples, and they observed RNase 1 immunostaining in hyperplastic ducts adjacent to one of the well-differentiated adenocarcinomas. CONCLUSIONS: The expression levels of RNase 1 by tumor cells from pancreatic adenocarcinomas are consistent with the high RNase 1 levels found in the serum of most patients with pancreatic adenocarcinoma. This expression of RNase 1, which is an acinar protein, demonstrates that the patterns of gene expression in pancreatic adenocarcinoma are distinct from those of normal pancreatic duct cells. Conversely, RNase 1 expression levels in altered ductal cells from some chronic pancreatitis tissues and hyperplastic ducts from carcinoma tissues suggest that abnormal expression levels may be an early event in pancreatic tumorigenesis.     

Overexpression of p53 protein during pancreatitis.

Overexpression of p53 correlates with neoplasia in many cytological specimens. To test the specificity of overexpressed p53 as a tumour marker for the detection of pancreatic cancer, we analysed cytological specimens of pancreatic juice samples from patients with pancreatitis or pancreatic carcinoma (n = 42) for p53 protein overexpression. p53 protein overexpression was found in 59% of patients with pancreatitis and 67% of patients with pancreatic carcinoma. Thus, the assessment of p53 protein overexpression is not useful in the diagnosis of pancreatic cancer. Overexpressed p53 during pancreatitis appears to be wild-type p53. Overexpression of p53 may result from DNA damage occurring during chronic inflammation. It is well established that p53 can induce apoptosis upon DNA damage. Consequently, we found apoptotic cell death in five out of five tested cytological preparations from patients with pancreatitis as well as in one out of one pancreatic carcinoma specimen.     

胰腺癌组织存活素和极光B表达的相关性

目的探讨凋亡抑制蛋白存活素（survivin）和极光B(AURORA_B)在胰腺癌组织中的表达与生物学行为之间的关系及两者的相关性。方法用免疫组织化学SP法检测45例胰腺癌和8例慢性胰腺炎及7例正常胰腺组织切片的survivin和AURORA_B的表达。结果45例胰腺癌中survivin和AURORA_B蛋白的阳性表达率分别为75.55%和53.33%;两者在7例正常胰腺组织中均未发现阳性表达;两者在8例慢性胰腺炎组织中的阳性表达率分别为25%和0。survivin的表达与组织学分级有关（P<0.05）,而与临床分期和淋巴结转移关系不大（P>0.05）,AURORA_B的表达与临床分期和淋巴结转移有关（P<0.05）,而与组织学分级关系不大（P>0.05）;survivin与AURORA_B的表达密切相关（P<0.05）。两者的表达与患者的性别、年龄、肿瘤的大小及部位均无关。结论survivin和AURORA_B密切相关,可能在胰腺癌的发生、发展过程中起关键作用,可能为胰腺癌的治疗和预防提供了新的靶点。     

Over-expression of p53 nuclear oncoprotein in colorectal adenomas.

p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53 protein is undetectable by standard immunohistochemical staining and the over-expression found in neoplastic cells correlates with the presence of point mutations of evolutionary conserved regions of the p53 gene. We examined the expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17 tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19 moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4 Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1 which recognises p53 protein in conventionally fixed and processed histological material. We found that 15 out of 36 colorectal adenomas showed p53 immunoreactivity, although in 4 positive cases (26%) the staining was very focal (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas showed strong p53 immunoreactivity and this over-expression was correlated with increased cell proliferative rate as detected by the proliferating-cell-nuclear-antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%) colorectal adenocarcinomas as previously shown. Our data suggest that the p53 gene mutation, with the subsequent over-expression of the protein, occurs in colorectal adenomas and may therefore be a fundamental genetic event underlying the dysplasia and loss of proliferative control that are characteristic of adenomas with malignant potential.     

Human prostate adenocarcinomas express in-vivo messenger-rnas and protein products for platelet-derived growth factor-B and its receptor

In situ hybridization and immunocytochemistry studies have shown the in vivo expression of platelet-derived growth factor B (PDGF-B) and PDGF receptor (PDGF-R) beta mRNAs and their respective protein products in the malignant epithelial cells of eight primary human prostatic adenocarcinomas. Examination of five nonmalignant adjacent prostate tissues did not demonstrate significant expression of PDGF B and PDGF-R beta mRNAs or production of their respective protein products in nonmalignant epithelial cells. Expression of androgen receptor mRNA was shown to be present in the epithelial cells of all of the five nonmalignant adjacent prostate tissues. There was a significant reduction in the expression of androgen receptor mRNA in poorly differentiated regions, and a moderate reduction in the well differentiated regions of the malignant tissues. It appears that dedifferentiation of the tumor cells in prostatic adenocarcinomas is accompanied by a reduction in androgen receptor mRNA expression. The coexpression of PDGF and its receptor in the malignant epithelial cells of prostatic adenocarcinomas signifies an abnormal autocrine loop that may contribute to their growth and maintenance.     

Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9

The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to moderately differentiated ductal adenocarcinomas of the pancreas and all cystadenocarcinomas were positive for CA 242. The staining was most intense in the apical border of the cells, and in the intraluminal mucus. Only two out of seven poorly differentiated adenocarcinomas stained, and the number of positive cells was smaller than in well differentiated carcinomas. Only occasional cells were stained in one out of five anaplastic carcinomas. Part of large ducts were positive in 91% (21/23) specimens of chronic pancreatitis. In acute pancreatitis small terminal ducts, centro-acinar cells and some large ducts stained for CA 242. In normal pancreas only a few small terminal ducts were CA 242 positive. Carcinomas always stained more strongly for CA 242 than normal pancreatic tissue adjacent to the carcinoma. The results of CA 242 are compared with those of tumour marker antigens CA 50 and CA 19-9. Serum CA 242 levels were determined in 23 of the patients with pancreatic cancer using a fluoroimmunoassay. Fifteen (65%) patients had an elevated value. There was no clear-cut correlation between the serum levels and the immunohistochemical expression of the CA 242 antigen. The expression of CA 242 in pancreatic tissue resembles that of CA 50 and is similar to CA 19-9. The antigen is expressed in serum of many patients with pancreatic cancer and, therefore, is a potential candidate for a serum tumour marker.     

Immunohistochemical analysis of p53 and MIB-1 in tissue specimens obtained from endoscopic ultrasonography-guided fine needle aspiration biopsy for the diagnosis of solid pancreatic masses

Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has been shown to be a highly accurate technique for distinguishing benign from malignant pancreatic masses. In this study, we examined p53 immunohistochemical analysis in FNAB specimens obtained from solid pancreatic diseases, and prospectively evaluated clinical applications for the diagnosis of malignancy in combination routine histological examination. Tissue specimens obtained from 62 pancreatic masses (51 pancreatic cancers and 11 chronic pancreatitis) by EUS-FNAB were evaluated by routine histological examination and p53 immunostaining. The conventional EUS-FNA diagnostic test statistics for the pancreatic masses were as follows: 76% sensitivity, 91% specificity and 79% accuracy. p53 protein overexpression was observed in 67% patients with pancreatic cancer, but not in patients with chronic pancreatitis. If the diagnosis of malignancy was made using the combination of p53 protein overexpression and conventional histological examination, the diagnostic test statistics changed as follows: 90% sensitivity, 91% specificity and 92% accuracy. p53 immunostaining in combination with routine histological examination of EUS-FNAB may improve the diagnostic accuracy for pancreatic cancer.