p53、c-erbB-2和PCNA蛋白表达与大肠癌生物学行为的关系

目的　探讨 p5 3、c erbB 2、PCNA蛋白的表达与大肠癌的临床病理意义以及其对大肠癌预后判断的价值。方法　应用免疫组化技术对 5 3例大肠癌进行上述指标的表达及对比研究。结果　大肠癌p5 3、PCNA、c erbB 2阳性表达分别为 5 2 .83%、96 .2 3%、5 4 .72 %。p5 3、PCNA、c erbB 2共同阳性表达率为 37.74 % ,与大肠癌患者年龄、性别、发病部位、纤维的增生程度、淋巴细胞的浸润及组织学类型无关 (P >0 .0 5 ) ,与癌组织的浸润深度、淋巴结转移有关 (P <0 .0 5 )。纤维组织的增生程度与癌组织浸润程度呈负相关 (r1=- 0 .4 2 13,P <0 .0 5 )有参考价值。结论　p5 3、c erbB 2、PCNA的联合检测对判断大肠癌预后有参考价值。     

喉鳞癌组织中p53蛋白的表达及其临床意义

目的　探讨p5 3蛋白在喉鳞状细胞癌组织中的表达及其临床意义。方法　采用免疫组化技术检测p5 3蛋白在喉鳞癌、癌旁非典型增生组织及正常组织中的表达。结果　p5 3蛋白在喉鳞癌、癌旁和正常组织中阳性表达率分别为 5 3 .7%、3 8.1%和0 ,三者有显著性差异 (P <0 .0 5 ) ;重度非典型增生组织与中、轻度增生、癌旁单纯增生和癌旁正常黏膜 p5 3阳性表达分别有显著性差异 ,表达率分别为 68.8%、2 1.4%、16.7%、8.3 %和 0 ;在肿瘤浸润的前沿部 p5 3阳性表达显著强于浅表部 (P <0 .0 5 ) ;且癌巢边缘 p5 3表达显著强于中央部 (P <0 .0 5 ) ;p5 3阳性表达与喉鳞癌的分化、淋巴结转移有关 (P <0 .0 5 )。 结论　p5 3的过度表达可能为喉鳞癌的早期发生事件 ,癌旁组织中已发生p5 3基因突变的细胞可能是肿瘤复发的根源 ;p5 3表达与喉鳞癌的浸润生长、分化及转移有关 ,为判断预后的 1个有意义指标。     

新疆不同民族食管癌中p53、p16、Rb蛋白的表达及其意义

目的　探讨 p5 3、p16、Rb蛋白在新疆不同民族食管癌中的表达及意义。 方法　应用免疫组化技术检测 119例不同民族食管癌组织中 p5 3、p16、Rb蛋白的表达。 结果　新疆食管癌 p5 3、p16、Rb蛋白检出率在不同民族间的阳性表达率均无显著性差异 (P >0 .0 5 )。三者阳性表达率与组织学分级无关 (P >0 .0 5 ) ;p5 3、p16阳性均与肿瘤浸润深度以及淋巴结转移有关 (P <0 .0 5 ) ,而Rb阳性仅与淋巴结转移有关 (P <0 .0 5 )。Rb与p16的表达密切相关 (P <0 .0 1)。结论　 1.食管癌组织内三者蛋白表达在新疆不同民族之间无显著性差异。 2 .检测三者蛋白的表达有助于判断食管癌的恶性程度以及推断临床预后。     

p16、p63蛋白在甲状腺肿瘤中的表达及其意义

目的　探讨抑癌基因蛋白p16和 p63在各型甲状腺肿瘤中的表达及其意义。 方法　采用免疫组织化学 (EnvisionTM)法检测 60例甲状腺肿瘤细胞中 p16和 p63蛋白的表达情况。 结果　甲状腺腺瘤中 p16及 p63蛋白阳性表达率分别为 60 .0 % ( 18/3 0 )和 46.7% ( 14 / 3 0 ) ,明显高于甲状腺癌 ( 3 3 .3 % ,10 / 3 0 ;2 0 .0 % ,6/ 3 0 ) ,有显著性差异 (P <0 .0 5 )。甲状腺乳头状腺瘤中 p16和p63蛋白阳性表达率分别为 80 .0 % ( 12 / 15 )和 60 .0 % ( 9/ 15 ) ,明显高于甲状腺乳头状腺癌中阳性率 ( 3 3 .3 % ,5 / 15 ;2 0 .0 % ,3 / 15 ) ,有显著性差异 (P <0 .0 5 )。甲状腺滤泡状腺瘤中 p16和p63蛋白阳性表达率分别为 40 .0 % ( 6/ 15 )和 3 3 .3 % ( 5 / 15 ) ,高于甲状腺滤泡状腺癌中其阳性表达率 ( 3 3 .3 % ,5 / 15 ;2 0 .0 % ,3 / 15 ) ,但无显著性差异 (P >0 .0 5 )。结论　检测甲状腺癌中p16和 p63蛋白表达水平 ,对甲状腺恶性肿瘤的诊断和预后评估有一定意义     

p16和p27蛋白在乳腺癌的表达及其意义

目的 :探讨p16和p2 7在乳腺癌的表达特点及其判断乳腺癌患者预后的意义。方法 :应用免疫组化ABC法检测 89例乳腺癌的p16、p2 7的表达情况。结果 :89例乳腺癌中 ,p16蛋白阳性表达率4 8 3% (4 3/ 89) ,p2 7蛋白阳性表达率 57.3% (51/ 89)。p16蛋白在腋淋巴结转移阳性组表达率 31.8%(14/ 4 4 ) ,显著低于腋淋巴结转移阴性组表达率 6 4 .4 % (2 9/ 4 5) (P <0 .0 1)。p2 7蛋白在浸润性乳腺癌组和腋淋巴结转移阳性组表达率分别为 52 .0 % (39/ 75)、38.6 (17/ 4 4 ) ,显著低于非浸润性乳癌腺组和腋淋巴结转移阴性组的表达率 85.7% (12 / 14)、75.6 % (34/ 4 5) (P <0 .0 5、P <0 .0 1)。结论 :p16蛋白与p2 7蛋白的缺失表达均与乳腺癌的生物学行为有关。p2 7蛋白检测在判断乳腺癌患者预后方面比p16蛋白检测可能有更重要意义。     

肿瘤转移抑制基因蛋白在不同恶性肿瘤组织中表达的检测

目的　研究肿瘤转移抑制基因蛋白在不同恶性肿瘤组织中的表达。方法　采用流式细胞术对 12 6例癌组织nm 2 3阳性、DCC阳性、p16阳性和 p5 3V阳性细胞检出率进行了检测。 结果　不同肿瘤患者癌组织的nm 2 3阳性、DCC阳性、p16阳性和p5 3V阳性细胞检出率分别为 (60 .0 2± 2 6.5 5 ) %、(5 1.16± 2 5 .2 5 ) %、(12 .47± 6.0 5 ) %及 (18.3 1± 10 .5 4) % ,前三者与正常对照比较均有显著性差异 (P <0 .0 1或P <0 .0 5 ) ,而后者极显著高于正常对照 (P <0 .0 1)。肿瘤转移患者的nm 2 3阳性、DDC阳性、p16阳性和 p5 3V阳性细胞检出率分别为 (4 8.82± 3 2 .2 5 ) %、(3 1.2 3± 2 2 .69) %、(5 .84± 4.70 ) %和 (2 9.67± 18.3 7) %。前三者显著低于未转移者 (P <0 .0 1或P <0 .0 5 ) ,而p5 3V阳性细胞检出率显著高于未转移者 (P <0 .0 1)。结论　恶性肿瘤患者癌组织中nm 2 3、DCC、p16表达水平明显下降 ,伴肿瘤转移者更为显著。肿瘤转移抑制基因蛋白表达的检测 ,对恶性肿瘤的诊断和转移潜能的判断有一定的意义     

cyclinD1及p16蛋白在大肠癌中的表达及与预后的关系

目的：研究cyclinD1（周期素D1）及p16基因表达的蛋白产物在大肠癌组织中的表达及与预后的关系.方法：应用免疫组化ABC法,在55例原发性大肠癌中检测cyclinD1及p16蛋白的表达.结果：cyclinD1蛋白表达阳性率为43.64%（24/55）;p16蛋白阳性表达率为47.27%（26/55）,cyclinD1与p16阳性表达与正常结肠直肠粘膜组织之间有非常显著性差异;cyclinD1阳性表达率在死亡组（64.70%,11/17）与生存组（28.57%,6/21）之间有非常显著性差异（P〈0.01）;p16蛋白阳性表达率在死亡组（5.85%,1/17）与生存组（42.86%,9/21）亦有显著性差异（P〈0.05）.结论：大肠癌发生过程中,存在cyclinD1及p16蛋白表达的异常,p16及cyclinD1过度表达与患者的预后密切相关,对肿瘤预后评估有重要意义.     

HIF-1α和iNOS在大肠癌组织血管形成中的作用

目的　探讨缺氧诱导因子 1α(HIF 1α)和诱导型一氧化氮合酶 (iNOS)在大肠癌血管形成中的作用。方法　采用免疫组化S P法 ,检测 62例大肠癌组织及 10例癌旁正常组织中HIF 1α和iNOS蛋白的表达 ,并用CD3 4标记血管内皮细胞 ,计算微血管密度 (MVD )。结果　 62例大肠癌组织中 ,HIF 1α、iNOS蛋白阳性表达率分别为 43 .5 % ( 2 7/62 ) ,5 6.5 % ( 3 5 /62 ) ,MVD平均值为 2 8.3± 17.5。HIF 1α、iNOS蛋白阳性表达率及MVD与癌组织Dukes分期显著相关 (P均 <0 .0 5 )。HIF 1α与iNOS表达一致符合率为 5 1.6% ( 3 2 /62 ) ,两者表达显著相关 (P <0 .0 5 )。HIF 1α、iNOS均阳性的大肠癌组织MVD高于两者均为阴性者 ,有显著性差异 (P <0 .0 5 )。结论　大肠癌组织存在HIF 1α蛋白的过表达 ,HIF 1α诱导iNOS蛋白表达 ,协同促进肿瘤新血管形成。HIF 1α、iNOS及MVD的测定可作为判断大肠癌转移潜能的重要指标     

不同分化程度大肠癌组织RAB5A和CD44v9的表达及其相关性分析

目的　检测RAB5A蛋白在高低不同分化程度大肠癌组织中的表达及其与CD4 4v9的相关性。方法　分别应用二步免疫组化和原位杂交法对 4 3例高低不同分化程度的大肠癌石蜡包埋标本进行检测。结果　 4 3例大肠癌组织中 ,RAB5A蛋白表达阳性率达 10 0 % (4 3/ 4 3) ,阳性表达位于胞质和胞膜 ;CD4 4v9表达阳性率为 81.4 % (35 / 4 3) ,阳性表达位于胞质。高低分化程度不同者RAB5A和CD4 4v9的表达程度差异有显著性 (P <0 .0 1) ,随着大肠癌分化程度的降低 ,表达明显增高。两者表达呈正相关性 (P <0 .0 1)。结论　RAB5A蛋白和CD4 4v9在大肠癌进展和分化过程中起着共同调节作用 ,可作为预测肿瘤分化程度和预后的客观指标。     

p27 蛋白在喉癌组织中的表达及其临床意义

目的 :探讨细胞周期调控因子p2 7蛋白在喉癌组织中的表达及临床意义。方法 :采用免疫组织化学SP法检测41例喉癌组织中 p2 7蛋白的表达 ,并与 12例癌旁正常组织作对照 ,进行比较分析。结果 :41例喉癌组织中p2 7蛋白的阳性表达率为 2 6 8% ( 11/4 1) ,12例癌旁正常组织阳性率为 5 8 3 % ( 7/12 ) ,二者差异有统计学意义 ,P <0 0 5。p2 7蛋白阳性表达率与喉癌患者的不同性别、年龄、病程、肿瘤部位、TNM分期以及淋巴结有无转移无关 ,P >0 0 5 ;患者吸烟 ( 14 3 % )和饮酒组 ( 10 0 % )与各自对照组 ( 5 3 8%和45 0 % )差异有统计学意义 ,P <0 0 5 ;与喉癌组织的病理分级差异有统计学意义 ,P <0 0 1。结论 :p2 7蛋白在喉癌的发生、发展过程中起着一定的作用 ,可作为判断喉癌恶性程度的一个重要参考指标     

Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis.

BACKGROUND AND METHODS. The expression of p53 protein in 100 large bowel cancers was studied immunohistochemically by use of a monoclonal antibody (PAb1801). RESULTS. Immunoreactivity was found in 61.0% of specimens from 100 patients with colorectal cancer. The pattern of p53 expression was mainly detected in the nuclei of the cancer cells. There was no significant correlation between the expression of p53 and the histologic grade, tumor size, serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, or liver metastasis. However, patients with p53-positive tumors had a greater relative risk of death compared with those with p53-negative tumors. The p53 negative-tumors showed a recurrence rate of 5.9%; for the p53 positive-tumors, a recurrence rate of 23.8% was recorded. The 3-year survival rate was 96.7% of 39 patients with p53-negative carcinomas and 61.8% for the patients with p53-positive tumors; there was a significant difference in the rate between the two groups of patients (P < 0.05). The growth fraction of p53-positive tumors determined with a monoclonal antibody against DNA polymerase alpha (49.0%) was significantly higher than that of p53-negative tumors (40.7%, P < 0.01). CONCLUSIONS. These results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance.     

Bcl-2 and p53 expressions in invasive bladder cancers

We investigated the Bcl-2 and P53 protein expressions in 89 patients with bladder cancers using immunohistochemical analysis. In superficial tumors, the times of tumor recurrence and progression were significantly shorter in the P53-positive group than in the negative group (p < 0.005, p < 0.05, respectively). In invasive tumors, the disease-specific actuarial survivals were significantly lower in the P53 and Bcl-2-positive groups (p <0.05, p < 0.025, respectively). In multivariate analysis, overexpression of p53 and Bcl-2 had independent prognostic value for survivals in invasive tumor, while disease-free survival was related independently to overexpression of p53 in superficial tumor. The results of our assessment for chemoeffectiveness revealed that the patients with Bcl-2-positive tumors had significantly lower response rates than those with Bcl-2-negative tumors (p < 0.05). We conclude that p53 expression is an independent, poor prognostic marker in invasive tumors as well as in superficial tumors and that overexpression of Bcl-2 is independently associated with a reduced-survival in patients with invasive tumors. These prognostic differences related to P53 and Bcl-2 expression in invasive bladder cancers may be partly due to chemo- or radio-sensitivity in relation to apoptotic process.     

Immunohistochemical analysis of p53 in colorectal cancer regarding clinicopathological correlation and prognostic significance

The overexpression of the tumor suppressor gene p53 was investigated immunohistochemically in 144 cases of primary colorectal cancer and in 8 cases with cancer in the corresponding metastatic lymph nodes. Abnormalities in p53 expression were found in 36 cases (25%) of the 144 primary cancer cases. In addition, p53-positive tumors were found to metastasize frequently to the lymph nodes, as compared to p53-negative tumors (61.1% vs. 41.7%, P=0.0428). p53 staining was identical in 7 of 8 (87.5%) cases in primary and metastatic lesions. When the DNA content of the tumor was determined by flow cytometry, the DNA index (mean ± SD) was significantly higher in p53-positive tumors than in p53-negative tumors (1.57 ± 0.38 vs. 1.39 ± 0.37, P=0.012). Therefore, the immunohistochemical data of p53 in colorectal cancer may help in potentially predicting metastatic spread to the lymph nodes. © 1995 Wiley-Liss, Inc.     

ASSOCIATION OF EXPRESSION OF P53 PROTEIN WITH CELL PROLIFERATIVE ACTIVITY AND PROGNOSIS IN COLORECTAL CANCER

p53gene,oneofwellknowntumorsuppressergenes,hasthecell-cyclenegatlveregulatlngfunctlonandregulatescellprollferatlon.'-'Themutatlonsandexpresslonofp53genelncolorectalcancerhavebeenstudledcomprehenslvely,butfewreportsdlscussedtherelatlonshlpofltsexpresslontocellprollferatlveactlvlty,lymphnodemetastaslsaswellasprognoslsofthedlsease.Weherebylnvestlgatedexpresslonofp53protelnandprollferatlngcellnuclearantlgen(PCNA)lncolorectalcancerwlthAB-PAPlmmuno-hlstochemlcaltechnlquetoflndoutthecorrelatlonbet…     

Correlations between HER2 Expression and Other Prognostic Factors in Breast Cancer: Inverse Relations with the Ki-67 Index and P53 Status

Background: Overexpression or amplification of human epidermal growth factor receptor-2 (HER2) is associated with grade of malignancy and a poor prognosis in breast cancer (BC). The aim of this study was to evaluate of value of HER2 as a prognostic marker, and to analyze associations with common histopathological parameters in BC cases. Materials and Methods: Between of 2007 to 2014, 260 patients with BC referred to Oncology Clinic provided cancer tissue samples which underwent immunohistochemistry (IHC) for markers. ER and PR positivity was defined as 10% positive tumor cells with nuclear staining. HER2-positive was defined as either HER2 gene amplification by fluorescent in situ hybridization (FISH) or scored as 3 by IHC. For HER2 (2), FISH was performed to determine HER2 positivity. Results: The mean age at diagnosis for the patients with HER2-negative was significantly higher than in HER2-positive cases. Also, there were significant correlations between histological grade, nuclear grade, lymph node metastasis, tumor size, ER status, PR status, p53 overexpression and Ki-67 index with HER2 expression. HER2-negative lesions were of higher grade and more likely to be ER-negative, PR-negative, p53-positive, lymph node metastasis, with a tumor sizealso Ki-6720% as compared to the HER2-positive group. Conclusions: Contrary to the results of other studies, HER2-positive tumors in our study had a lower Ki-67 index and were p53-positive. Also, Ki-67 proliferation index 20% in more studies was associated with p53-positive.Therefore, tumors which are HER2-positive and have a Ki-6720% had a more aggressive behavior compared to HER2-positive and Ki-67<20% lesions.     

Expression of phosphorylated Akt (pAkt) in gastric carcinoma predicts prognosis and efficacy of chemotherapy

BACKGROUND: The Akt signaling pathway controls the survival and growth of human cancers. We investigated the expression of phosphorylated Akt (pAkt) in patients with gastric cancer. METHODS: The expression of pAkt was immunohistochemically examined in 140 gastric cancer patients who underwent a gastrectomy. The expression of pAkt was evaluated based on staining intensity, and staining was classified as negative or positive. We examined the expression of pAkt and its association with the clinicopathological findings, prognosis, depth of invasion, the expression of p53, and efficacy of oral fluorouracil chemotherapy after surgery. RESULTS: Expression of pAkt was positive in 81 (58%) patients and negative in 59 (42%) patients. There were no significant correlations between pAkt expression and the clinicopathological findings. The prognosis of patients with pAkt-negative tumors was superior to that of patients with pAkt-positive tumors, and the difference was significant for T3/T4 gastric cancer (P < 0.05). Among the patients with T3/T4 gastric cancer, postoperative oral fluorouracil treatment was effective in those who were pAkt-positive. Multivariate analysis revealed that pAkt expression and lymph node metastasis were independent prognostic factors. In 88 patients with T3 gastric carcinoma who had undergone curative surgery, in whom we studied the prognostic impact of a combined analysis of pAkt and p53 expression, patients with both pAkt- and p53-positive tumors showed a significantly poorer prognosis than patients with either or both pAkt- and p53-negative tumors (P < 0.05). CONCLUSION: Our results indicate that pAkt expression may be useful for predicting the prognosis and efficacy of fluorouracil treatment in patients with gastric cancer.     

MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency

Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4 %) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor–node–metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4 % (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan–Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC–pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular.     

非小细胞肺癌组织中bcl-2和mt-p53蛋白表达与血管生成的关系及其意义

目的:探讨非小细胞肺癌组织(NSCLC)中bcl-2及mt-p53蛋白表达与血管生成的关系。方法:采用免疫组化s-p法检测60例NSCLC标本中bcl-2、mt-p53蛋白表达,以血管内皮细胞表面抗原CD34单抗标记测定MVD。结果:在NSCLC中bcl-2阳性率31.67%,bcl-2阳性率与分化程度有关(P<0.05),mt-p53表达阳性率为48.33%;MVD以及mt-p53表达与NSCLC的淋巴转移(P<0.05)有关,MVD低表达者术后生存期明显长于高表达组(P<0.01);bcl-2阳性组病人中mt-p53阳性率明显低于bcl-2阴性组(P<0.05),bcl-2阳性组MVD明显低于bcl-2表达阴性组(P<0.05),相反,mt-p53阳性组MVD高于阴性组(P<0.01);在NSCLC中,在bcl-2阴性病人中mt-p53( )组MVD(21.39±6.35)与mt-p53(-)组之间的MVD(15.91±5.68)存在显著性差异(P<0.01),但在bcl-2阳性病人中二组之间无显著差异(P>0.05)。结论:NSCLCbcl-2基因高表达可能与肿瘤血管生成的抑制有关,mt-p53基因则可能通过下调bcl-2促进肿瘤血管生成。     

Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma. Int. J. Cancer 74:310-315, 1997. © 1997 Wiley-Liss, Inc.