抑癌基因p53在不同地区食管癌中的表达及临床预后分析

目的：比较中国食管癌高，低发区p53蛋白的积聚，燕对p53蛋白积聚与肿瘤细胞增殖及临床预后的关系进行探讨。方法：用免疫组化LSAB法检测高发区（河南）43例食管癌和低发区（广东）40例食管癌p53蛋白及增殖细胞核抗原的表达。结果：p53蛋白阳性率分别是60．5％（河南）和57．5％（广东）。阳性率差异无显著性（P＞0．05）。p53蛋白表达无论在高，低发区均与PCNA的表达密切相关（P＜0．001）。结论：食管癌不同的高，低发区中p53蛋白的各聚是类同的。大多数p53蛋白积聚的肿瘤细胞是处于细胞增殖周期内，可能成为食管癌恶性程度的指标之一，将为临床分析预后提供客观依据。     

Prognostic significance of p53 overexpression in gastric and colorectal carcinoma.

p53 expression was examined in 55 gastric and 107 colorectal carcinomas with an immunoperoxidase technique, using the polyclonal antibody CM1 on routinely fixed, paraffin embedded tissue. p53 protein was detected in 47% gastric and in 46% colorectal carcinomas and found to correlate with stage of disease and unfavourable clinical outcome (P less than 0.001). Thus, the proportion of positively reacting neoplasms increased as the stage progressed, tumours which had invaded regional lymph-nodes overexpressed p53 more frequently than localised carcinomas and an elevated level of p53 was associated with early relapse and death. In colorectal carcinoma p53 positivity was also linked with site and macroscopic configuration of the primary tumour and was most frequently expressed in carcinomas from the rectum and in ulcerative tumours. p53 overexpression was irrespective of tumour grade. Uniform negative reactivity with anti-p53 antibody was seen in normal epithelium adjacent to carcinoma, intestinal metaplasia, atrophic gastritis and in colonic adenomas. There was a good correlation between immunohistochemical staining on paraffin and frozen sections. These studies suggest that in gastric and colorectal carcinoma, immunohistochemical detection of p53 protein in routinely fixed tissue can be used along with other established parameters to assess prognostic outcome, especially to identify patients with poor short-term prognosis.     

A comparative immunohistochemical study of p53 and proliferating-cell nuclear antigen expression in microwave-fixed paraffin sections of colorectal tumors

This paper reports on a comparative immunohistochemical study of p53 and proliferating-cell nuclear antigen (PCNA) performed on microwave (MW)-fixed paraffin sections of 24 colorectal carcinomas and 68 adenomas in order to investigate the relationship between p53 expression and proliferative activity. Nuclear p53 was detected in 12 cases out of 24 carcinomas and eight out of 68 adenomas were found to focally express p53. Examination of PCNA expression in the adjacent sections of carcinomas revealed that the incidence of PCNA expression was not affected by p53, and both p53-positive and p53-negative carcinomas exhibited a high level of PCNA expression that reached more than 75% of the cancer cells. In the colorectal adenomas, the incidence of PCNA expression averaged about 30% although highly heterogenous distribution of PCNA-positive cells in the section was observed. When we examined eight adenomas positive for p53, the incidence of PCNA expression in the p53-positive glands of each adenoma was significantly higher (52.1%) than that in the neighboring glands without p53 expression (36.5%) (p<0.05). The results indicate that the abnormal expression of p53 in colorectal adenomas may reflect a failure in the control of cell proliferation. Furthermore, lack of the association of p53 expression with proliferative activity in colorectal carcinomas implies that several gene alterations together with p53 may be responsible for the complete loss of the regulatory mechanism for cell proliferation.     

Telomerase, p53 and PCNA activity in osteosarcoma.

AIMS: The aim of this study was to investigate telomerase activity and to assess the correlation between telomerase activity, tumor proliferative activity and p53 overexpression in osteosarcoma tumor samples. METHODS: Using a telomerase polymerase chain reaction-enzyme-linked immunoassay based on the telomeric repeat amplification protocol method, we examined telomerase activity in 26 primary osteosarcoma specimens. P53 overexpression was identified using immunohistochemical staining, and tumor proliferative activity was assessed by immunohistochemical staining of PCNA. RESULTS: Telomerase activity was detected at a relatively low level in five of 26 osteosarcoma tissue specimens. P53 was detected in eight of 21 cases. There was no significant correlation between telomerase activity and p53 overexpression (p=0.325). There was a significant correlation between PCNA staining and telomerase activity (p=0.0075). CONCLUSION: Difference between the telomerase activity and p53 overexpression in osteosarcoma suggests that p53 and telomerase may not cooperate in tumor proliferation. Correlation of telomerase activity to PCNA expression suggests that telomerase activity may also useful for evaluate proliferative activity in osteosarcoma.     

P53和P21过表达与胃癌淋巴结转移呈正相关

应用Ｓ－Ｐ免疫组化方法研究Ｐ５３和Ｐ２１表达变化与胃癌肿瘤组织分型、细胞增殖和浸润深度及淋巴结转移的关系。发现Ｐ５３阳性染色率为４８．９％，Ｐ５３阳性染色与胃癌肿瘤浸润深度及癌细胞增殖活性呈正相关（Ｐｅａｒｓｏｎ列联系数分别为Ｐ＝０．３２和Ｐ＝０．３５，Ｐ＜０．０５）。同时发现Ｐ２１阳性染色率为７０．０％，Ｐ２１阳性染色与胃癌肿瘤组织分型及癌细胞增殖活性呈正相关（Ｐｅａｒｓｏｎ列联系数分别为Ｐ＝０．３３和Ｐ＝０．５２，Ｐ＜０．０５）。Ｐ５３和Ｐ２１阳性肿瘤的淋巴结转移率（９３％和８１％）分别均明显高于其阴性表达的肿瘤（６０％和５５．５％，Ｐ＜０．０５）。Ｐ５３和Ｐ２１过表达对胃癌淋巴结转移率的贡献为以Ｐ５３过表达为主的独立的联合作用。提示Ｐ５３和Ｐ２１过表达在胃癌淋巴结转移和肿瘤增殖中起重要作用。Ｐ５３过表达与肿瘤浸润有关，而Ｐ２１过表达与肿瘤组织分型有关。     

Preoperatively irradiated rectal carcinoma: analysis of the histopathologic response and predictive value of proliferating cell nuclear antigen immunostaining

OBJECTIVES: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. METHODS: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. RESULTS: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07-26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. CONCLUSION: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.     

Overexpressions of Ha-ras and p53 predict the prognosis of patients with non-small-cell lung carcinoma

Activationofprotooncogenesandinactivationoftumor-suppressorgeneshavebeenshowntoplayanimportantroleincarcinogenesis.Inhumantumors,alterationsoftherasprotooncogenesandp53tumor-suppressorgenehavebeenwidelyinvestigated[1-6].Thethreemembersoftherasprotooncogenefamily,Ki-ras,Ha-ras,andN-ras,encodep2l(ras)[ras][1,2].Pointmutationsoftherasprotooncogenes,resultinginmutatedformsofrasp21,andanenhancedexpressionofthenormalcellularrasp2laretwomechanismsknowntoleadtoactivationoftherasprotooncogenefamily[7,…     

乳腺癌雌激素受体表达与p53、PCNA、AgNOR表达关系

目的 研究乳腺癌雌激素受体（ＥＲ）表达与ｐ５３,增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｏｎ ｃｅｌｌ ｍｕｃｌｅａｒ ａｎｔｉｇｅｎ,ＰＣＮＡ）表达和银染核仁组成区（ＡｇＮＯＲ）计数关系。方法 采用ＡｇＮＯＲ染色技术和免疫组化Ｓ－Ｐ法,用抗ＥＲ,抗ｐ５３（ＤＯ－７）及抗ＰＣＮＡ（ＰＣ１０）单克隆抗体,研究５０例乳腺癌ＡｇＮＯＲ计数及ＥＲ,ｐ５３,ＰＣＮＡ表达。结果 乳腺癌３３例（６６％）ＥＲ表达阳     

Effects of p53 overexpression on neoplastic cell proliferation and apoptosis in thymic carcinoma

Wild-type p53 protein could regulate cell proliferation and apoptosis. Loss of its function aught play acrucial role in tumourigenesis of some malig nancies.l']The inactivation of p53 protein could be resulting fromp53 gene mutation or binding with other cellular or viralproteins, such as mdm-2 or ZEBRA encoded byEPstein-Bars virus.12] Thyndc carcinoma is a rare thyndcepithelial malignancy. Does p53 protein overexpressiondevelop in thyndc carcinomas? If so, what role does p53overexpression…     

Expression of bax and p53 proteins in the tumorigenesis and progression of breast carcinomas.

OBJECTIVES: Dysregulation of normal programmed cell death mechanisms plays an important role in the pathogenesis of breast cancer. The purpose of this study was to investigate the role of bax and p53 expression in tumorigenesis and progression of breast carcinoma as well as their relationship with proliferative and apoptotic activity. METHODS: We used immunohistochemical methods and in situ detection of apoptotic cells to examine 30 carcinomas in situ (CIS), 131 invasive breast carcinomas and 45 lymph node metastases. RESULTS: In 25% (33 of 131) of invasive breast carcinomas examined, bax expression was absent, while p53 accumulation was present in 37% (49 of 131). Interestingly, p53 accumulation and loss of bax expression occur in breast CIS as frequently as in invasive breast carcinoma. Thus, in 17% (5 of 30) of CIS bax expression was absent, and 30% (9 of 30) presented nuclear expression of p53. p53 accumulation was related to apoptosis and proliferative activity. However, the protein level of bax was unrelated to all parameters studied, including proliferation and apoptosis of tumor cells. A multivariate analysis of disease-free survival demonstrated that p53 accumulation and bax expression are not significant independent indicators of prognosis in operable breast carcinoma. Our results also show that the proportion of bax- and p53-positive cells does not vary between primary and metastatic tumors. CONCLUSIONS: p53 accumulation and loss of bax expression influence the acquisition of a malignant phenotype but seem to have no further impact on tumor progression.     

食管癌中P16、PCNA基因蛋白的表达及意义

 目的：探讨P16、PCNA基因蛋白表达与食管鳞癌发生发展的关系。方法：应用S-P免疫组织化学方法对84例食管鳞癌及10例正常食管组织分别检测P16蛋白、PCNA蛋白表达。结果：84例食管鳞癌中P16蛋白表达率为54.8%(47/84),P16表达与淋巴结转移、临床分期、术后生存期显著相关(P<0.05);PCNA表达阳性率与食管癌组织分化程度显著性正相关(P<0.05),淋巴结转移组显著高于未转移组,并与术后生存期互相关(P<0.01),与临床分期无显著相关。P16与PCNA表达呈反相关系(P<0.01)。结论：表明P16在食管癌生长、转移中起重要作用,P16、PCNA可作为判断预后的重要指标。     

食管癌组织中COX-2、p53和PCNA的表达及意义

目的 :研究食管癌组织中环氧合酶 2 (COX 2 )、p53和增殖细胞核抗原 (PCNA)的表达及意义。方法 :采用免疫组化染色 (EnVision及S P)法 ,检测 82例食管鳞状细胞癌、2 0例食管炎和 1 6例正常食管粘膜组织标本中COX 2、P53和PCNA的表达。结果 :82例食管癌组织中COX 2、p53和PCNA的阳性表达率分别为 87.8% (72 82 ) ,82 .9% (68 82 )和 95 .1 % (78 82 ) ,而癌旁及正常组织中均呈阴性表达。COX 2在高分化和中分化食管癌中的表达率显著高于低分化癌 (P <0 .0 1 ) ;无淋巴结转移者表达率高于有淋巴结转移者 (P <0 .0 5)。p53的过表达与浸润深度和淋巴结转移呈正相关 (P <0 .0 1 )。结论 :COX 2、P53和PCNA的过表达可能均参与了食管癌的发生发展过程     

Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.

BACKGROUND: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. PURPOSE: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. RESULTS: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. CONCLUSIONS: Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.     

Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative administration of 5-fluorouracil

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.     

肺鳞癌免疫组化彩色图像定量分析

目的：探讨肺鳞癌免疫组化图像定量分析中描述图像色彩的指标在不同分化程度间的变化及作用。方法：采用S－P法进行肺癌p53,PCNA和p16免疫组化染色,应用计算机病理图像分析系统（MPIAS－500）进行图像分析。结果：20例肺鳞癌患者中没有高分化者,中分化组和低分化组P53阳性均为6例,PCNA阳性分别为7例和6例,P16阳性分别为5例和6例,中分化组P53染色的饱和度（4．95％）低于低分化组（10．95％）,两者差异有显著性（t=4.208,P=0.002)。中分化组PCNA染色的饱和度（7．74％）亦低于低分化组（12．98％）,差异有显著性（t=2.416,P\0.034);中分化组P16染色的色度（53．98度）低于低分化组（62．32度）,差异有显著性（t=2.784,P=0.021)。结论：用描述图像色彩的指标定量分析肺鳞癌免疫组化图像可能反应肺癌的不同分化程度。     

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.     

食管鳞癌特殊亚型的免疫组化表型及其增殖活性的研究

目的：探讨食管鳞癌特殊亚型的免疫组化表型和细胞增殖活性。方法：用免疫组化S－P法检测鳞癌4种亚型的免疫组化表型、PCNA和p53蛋白。结果：（1）这些亚型的免疫组化表型与其形态分化有关；（2）PCNA和p53蛋白在梭形细胞鳞癌（SCSC）和基底细胞样鳞癌（BSC）中表达更为显著。结论：在食管鳞癌特殊亚型中，SCSC和BSC型，尤其是后者具有低分化高增殖活性以及明显的临床侵袭行为。     

PCNA、P53的过度表达与喉鳞癌预后的关系

 探讨PCNA、P⁵³的过度表达与喉癌预后的关系.方法:应用免疫组化ABC法对56例喉鳞癌和7例喉正常组织检测.结果:56例喉癌中,PCNA、P⁵³阳性率分别为71.4% 和 51.8%.正常组织染色阴性.喉癌的临床分期、有无淋巴结转移和患者术后3年生存率与PCNA、P⁵³ 阳性表达率关系密切.结论: PCNA、P⁵³的过度表达与喉癌的不良预后有关.     

p53、p16蛋白及增殖细胞核抗原与胃癌生物学行为的关系

目的　探讨p5 3、p16蛋白及增殖细胞核抗原 (PCNA)异常表达与胃癌生物学行为的关系。方法　应用免疫组化ABC法 ,对 95例胃癌进行p5 3、p16蛋白表达产物和PCNA进行检测。结果　胃癌组织中p5 3、p16、PCNA阳性率分别为 49 5 % ( 4 7/ 95 )、2 0 0 % ( 19/95 )、78 9% ( 75 / 95 )。p5 3蛋白、PCNA在进展期胃癌 ( 5 3 5 %、82 6% )淋巴结阳性胃癌 ( 5 9 3 %、86 4% )表达率均高于早期胃癌( 11 1%、44 4% )和淋巴结阴性胃癌 ( 3 3 3 %、66 7% ) (P <0 0 5 )。p5 3蛋白、PCNA在累及浆膜胃癌的表达率高于局限粘膜及粘膜下层胃癌 (P <0 0 5 ,P <0 0 1)。PCNA异常表达与胃癌组织学分型有关 (P <0 0 5 )。p16蛋白表达与胃癌大多数生物学行为无明显关系 ,但其在淋巴结阳性胃癌中的表达率 ( 11 9% )低于淋巴结阴性胃癌中的表达率 ( 3 3 3 % ) (P <0 0 5 )。p5 3阳性组织大多数伴PCNA阳性表达 (P <0 0 1)。结论　p5 3蛋白、PCNA异常表达在胃癌浸润转移过程及增殖中均起重要作用。p16蛋白表达缺失可能是胃癌淋巴结转移的重要促发因素。     

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.