直肠癌P21、P53基因表达及其临床意义

 目的: 研究P²¹、P⁵³基因在直肠癌组织中的表达情况与直肠癌病理特征的关系及其在预后判定方面的意义。方法: 采用SP免疫组化法对110例手术后石蜡包埋标本行P²¹、P⁵³基因表达检测, 同时选用正常组织为实验对照。结果: 直肠癌组织P²¹、P⁵³基因表达阳性率分别为54.5 %、42.7 %;P53组织表达情况与临床病理因素无相关性; P²¹表达阳性病例3 、5年生存率降低, 组 织分化差, 淋巴转移率增高(P<0.05 %)。结论: P⁵³基因与直肠癌形成密切相关, 与直肠癌预后未见相关性。P²¹基因表达情况可能成为直肠癌的预后指标。     

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.     

鼻咽癌细菌L型、EB病毒感染的检测及与P21、P53基因突变的关系

 用免疫组化染色和革兰染色等技术,对129例鼻咽癌、20例鼻咽粘膜慢性支进行细菌L型、EB病毒检测,同时对L型阳性、EBV阳性和L型阴性、EBV阴性组织的P ²¹、P⁵³表达进行对比分析.结果显示,鼻咽癌组的L型检出率为69.8%;EBV检出率为27.1%,两者有显著性差异(P<0.05).鼻咽癌组的P²¹、P⁵³阳性表达率显著高于慢性炎组(P＜O.005).L型阳性、EBV阳性伴P²¹、P⁵³阳性的表达率也分别高于L型阴性、EBV阴性伴P²¹、P⁵³阳性的表达率.表明L型、EBV感染与鼻咽癌关系密切;P²¹、P⁵³过度表达与鼻咽癌的发生也有关.此外,L型和EBV感染与P²¹、P⁵³的过度表达存在着相关性.提示,L型和EBV参与了P²¹、P⁵³基因突变,并在鼻咽癌的发生中可能起协同作用.     

P53、P16蛋白在卵巢上皮癌中的表达

 目的:探索抑癌基因P⁵³、P¹⁶表达与卵巢上皮癌发生的关系。方法:采用免疫组化SP法对27例卵巢上皮癌组织中P⁵³蛋白,P¹⁶蛋白进行检测。结果:卵巢上皮癌P⁵³蛋白阳性表达率为44.44%。P¹⁶蛋白在卵巢上皮癌中表达阳性率为18.52%,P⁵³及P¹⁶表达与病理类型无关。P⁵³蛋白过度表达与临床分期无关。P¹⁶晚期表达阳性率明显减少(P<0.05)。结论:P⁵³、P¹⁶基因表达的改变在卵巢上皮癌发生中起重要的作用。     

P53及nm23在胃癌中的表达及其意义

 应用LSAB免疫组化方法研究P⁵³和nm23表达变化与胃癌生物学行为及淋巴结转移和预后的关系。发现P⁵³及nm23的阳性率分别为61%、60%。P⁵³过表达与淋巴结转移和预后关系密切(P<0.01)。nm23低表达与胃癌侵袭程度、淋巴结转移及预后有明显关系(P<0.01)。P⁵³过表达和nm23低表达在胃癌淋巴结转移及预后中可能起协同作用。提示检测P⁵³蛋白及nm23基因表达状况可作为临床预测胃癌淋巴结转移及预后的一项指标。     

子宫内膜癌c-erbB-2和P53基因蛋白表达及其与预后的关系研究

 采用免疫组织化学法检测了64例子宫内膜癌,16例正常子宫内膜,32例子宫内膜增殖症和5例子宫内膜息肉中的C-erbB-2和P⁵³基因蛋白表达情况并分析与其临床病理和预后的关系.结果:(1)c-erbB-2阳性表达率在内膜癌、内膜增殖症和正常内膜分别为60.9%、21.9%和18.8%.内膜息肉无阳性表达.P⁵³阳性表达率则分别为37.5%.3.l%和0.0%.癌组织与增殖症和正常内膜的c-erbB-2和P⁵³阳性表达率相比较,差异均有显著性(P＜O.05).(2)内膜组织中的c-erbB-2和P⁵³的阳性表达与临床分期和组织分级有相关性,而与病理类型,肌层浸润无关.(3)P⁵³和c-erbB-2表达阳性内膜癌患者的3、5年生存率明显低于阴性患者.上述结果表明,c-erbB-2和P⁵³与内膜癌的发生,发展密切相关,可作为评估其恶性生物学行为和预后的重要指标之一.     

三种癌基因蛋白产物在结肠癌的表达及意义

 用免疫组化方法检测4B例结肠良性病变和113例结肠癌中c－erbB－2、c－myc及P⁵³蛋白的表达。结果：三种癌基因蛋白产物在结肠癌中的表达显著高于结肠良性病变（P<0.01）。c－erbB－2、P⁵³蛋白表达与结肠癌淋巴结转移密切相关。P⁵³蛋白表达与结肠癌的分化程度有关。检测结肠癌组织中三种癌基因蛋白产物表达可作为结肠癌的诊断和判断预后的参考指标。     

恶性淋巴瘤中MTS1-p16基因的缺失

 目的 研究MTS1p¹⁶基因在恶性淋巴瘤中的变化。方法 采用多重PCR 检测34 例非何杰金淋巴瘤（NHL） 和15 例健康人体外周血DNA 的p¹⁶gene Exon2 纯合子缺失。结果 34 例NHL中有4 例有p¹⁶gene Exon2 纯合子缺失。结论 MTS1P¹⁶gene 变异可能在非何杰金淋巴瘤的发生发展中起作用。     

P53突变产物在睑板腺癌中的增强表达及其意义

 我们采用免疫组化S-P法, 对17例石蜡包埋睑板腺癌及癌旁组织标本的P⁵³突变蛋白表达进行了检测。 结果:17例癌组织有12例表达阳性, 阳性率71%。其中分化型7例, 6例呈阳性(86%)表达。在一组原发灶及淋巴结转移癌配对标本中, 同一病人之两个部位P⁵³突变蛋白表达差异无明显意义。 癌旁(睑缘)组织17例中5例上皮有异常增生, 且同时伴有P⁵³突变蛋白呈强阳性表达。 以上结果提示:抑癌基因P53的突变在睑板腺癌的发生中是一个比较常见的基因改变, 且在分化型癌的发生中表现明显; P⁵³基因异常发生在肿瘤转移之前且在淋巴道转移中可能起重要作用; P⁵³突变蛋白在癌旁上皮异型增生组织中的过度表达具有十分重要的意义。     

PCR-SSCP法检测宫颈癌P53基因突变

 目的：探讨抑癌基因P⁵³突变与宫颈癌发生发展之间的关系,并为该病的临床检测提供一种分子生物学方法。方法：应用多聚酶链反应－单链构象多态性（PCR SSCP）分析方法对宫颈癌及慢性宫颈炎组织中P⁵³基因5～6外显子的突变进行了检测。结果：35例宫颈癌组织中有2例出现突变,突变率为5.71%;而作为对照的慢性宫颈炎组织中无一例出现突变。结论：宫颈癌的发生与抑癌基因P⁵³5～6外显子的突变有关;此方法可有效地检测抑癌基因P⁵³的突变。     

儿童非霍奇金淋巴瘤53例临床分析

目的　总结 5 3例儿童非霍奇金淋巴瘤的临床特点及治疗方法。方法　回顾性分析 5 3例儿童非霍奇金淋巴瘤的临床症状、病理类型、诊断和治疗。结果　浅表淋巴结肿大为首发症状者 36例。全组误诊率 71 7%。病理类型主要为高度恶性 (31/ 5 3)。全组 5年生存率为 2 2 6 %。结论　儿童非霍奇金淋巴瘤为儿童常见肿瘤 ,恶性度高 ,误诊较为常见 ,治疗应以化疗为主配合局部放疗。     

转染P53基因对胶质瘤细胞株SHG44裸鼠致癌性的作用研究

 目的:探讨转染野生型P⁵³(wt-P⁵³)和突变型P⁵³(mtP⁵³)基因,对人胶质瘤细胞株SHG44裸鼠致瘤性的影响及意义.方法:采用质脂体介导法,分别将wt-P⁵³和mt-P⁵³基因导入人胶质瘤细胞株SHG44,体内外检测转导细胞的生长状况和裸鼠致瘤性.结果:转染mt-P⁵³基因的细胞株,G418筛选细胞集落数、软琼脂平皿细胞集落数以及裸鼠瘤组织重量和体积,均显著高于对照组(P <0.01);而转染Wt-P⁵³ 基因的细胞株均显著低于对照组(P<0.01),表明导入wt-P⁵³基因的细胞株,瘤细胞生长速度明显低于对照细胞株和导入.mt-P53基因的细胞株,即导入mt-P⁵³基因的细胞株瘤细胞生长速度最快,而导入Wt-P⁵³基因的细胞株瘤细胞生长速度最慢.结论:Wt-P⁵³基因能有效地抑制人胶质瘤细胞生长;mt-P⁵³基因则可以明显地促进瘤细胞生长.     

Mutation of the TP53 gene in acute lymphoblastic leukemia does not affect survival outcomes after haploidentical hematopoietic stem cell transplantation

Previous studies have demonstrated that TP53 mutation is correlated with insufficient therapy response and unfavorable prognosis in acute lymphoblastic leukemia (ALL). Few studies have investigated the impact of TP53 mutation in ALL patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We completed a retrospective study of 65 ALL patients with available TP53 status who underwent haplo-HSCT. They were divided into a TP53 mutation group (TP53^mut) and a TP53 wild-type (TP53^wt) group. TP53^mut showed comparable 2-year cumulative incidence of relapse (CIR) rates (13.1% vs 12.5%, P = .96) and 2-year leukemia-free survival (LFS) (74.2% vs 77.4%, P = .80) with TP53^wt. No significant differences in 2-year overall survival (OS) rates (82.9% vs 87.3%, P = .61) or 2-year NRM rates (12.7% vs 10.2%, P = .69) were observed in TP53^mut and TP53^wt patients. Multivariate analysis suggested that white blood cell (WBC) count at initial diagnosis (>50 × 10⁹/L: hazard ratio [HR] = 3.860, P = .016) and age (>40 years old: HR = 4.120, P = .012) are independent risk factors for 2-year LFS. Our study showed that TP53 mutations may not be related to the unfavorable impact on survival in ALL patients after treatment with haplo-HSCT. The present results suggested that haplo-HSCT may eliminate the poor prognosis effect of TP53 mutation in ALL.     

Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor

Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors.     

nm23和p53基因与肺腺癌生物学特性的关系

目的：检测肺腺癌组织中nm23表达和p53基因外显子突变情况,寻找有助于准确预测局部肿瘤进展、分型和预后情况的临床参照指标。方法：应用PCR技术检测31例肺腺癌术后存档蜡块组织中nm23表达及p53基因外显子突变情况,并与肺腺癌的病理及临床指标进行相关性分析。结果：nm23表达及p53基因突变率分别为38．7％（12／31）及48．4％（15／31）。nm23表达和p53基因突变与临床分期相关,P值分别为0．005、0．037。结论：nm23表达和p53基因突变与肺癌临床分期和生存相关,在判断肺腺癌细胞增殖、分化程度、恶性程度及预后转归方面有一定价值,可作为判断肺腺癌预后的参考指标,指导高危患者的进一步治疗。     

High prevalence of p53 exon 4 mutations in soft tissue sarcoma

BACKGROUND: p53 is the most commonly mutated gene in cancer, including soft tissue sarcoma (STS). The authors characterized p53 alterations (protein accumulation and gene mutation) in STS to evaluate possible associations with patient outcomes. METHODS: Thirty-one STS specimens (multiple histologies) were analyzed by p53 immunohistochemistry (IHC) and direct DNA sequencing of p53 exons 2-11 and then correlated with outcomes. RESULTS: Direct p53 sequencing detected mutations in 10 of 31 STSs; 7 of 10 were missense mutations, whereas 3 of 10 were either insertions or frameshift mutations, leading to nonfunctional truncated p53; 7 of these p53 mutations have not been previously described. Four p53 exon 4 mutations were identified, a p53 region previously unknown to be mutation prone. Eighteen of the 31 specimens expressed p53 when the authors used the clinical IHC assay of their institution. Interassay concordance of 48% was observed; only 6 of 10 sequencing-identified p53 mutated specimens exhibited nuclear p53 protein expression by IHC, whereas 12 of 18 specimens exhibiting p53 protein expression by IHC harbored sequencing-identified wild-type p53. Decreased survival was observed in STS patients bearing sequencing-identified mutated p53 versus wild-type p53, as was a correlation between IHC-determined nuclear p53 protein expression and decreased survival. CONCLUSIONS: p53 protein stabilization and p53 mutation frequently occur in STS, and both suggest worse outcomes for patients so affected. However, increased p53 protein expression does not necessarily indicate p53 gene mutation. The high incidence of exon 4 mutations found in STS suggests that p53 sequencing should not be limited to the core DNA binding domain.     

Constitutively overexpressed 21 kDa protein in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas identified as cytochrome B<Subscript>5b</Subscript> (CYB5B)

Background  

We have previously reported a novel constitutively overexpressed 21 kDa protein in Hodgkin Lymphoma (HL) and aggressive Non-Hodgkin Lymphomas (NHL). The objective of the current study was to 1) identify this protein using two independent methods, 2) study the expression of the protein and its encoding mRNA in reactive lymph nodes, normal lymphocytes and CD34+ bone marrow precursor cells, 3) analyse patterns of expression of the protein in tissue microarrays assembled from a large number of diagnostic clinical biopsies from patients with HL, and 4) determine the copy number variation and mutation status of the encoding gene in HL cell lines.     

有和无内分泌分化大肠癌P53和表皮生长因子受体表达的比较研究

 目的：研究大肠癌内分泌分化与P⁵³表皮生长因子受体（EGFR）表达的关系及意义。方法：采用免疫组织化学ABC法，检测79例大肠癌手术切除组织中嗜铬蛋白A（CGA），P⁵³及EGFR的表达变化。结果：大肠癌组织中CGA，P⁵³及EGFR的表达率分别为：35.4％（28/79〕，60.8％(48/79）和30.4％（24/79），有内分泌分化的大肠癌P⁵³表达率及其免疫阳性细胞数分别为78.6％（22/28）和984.3士702.0/mm²，无内分泌分化者分别为51.0％和589.5士489.5/mm²，前者明显高于后者（P53及EGFR的表达明显高于无内分泌分化者，提示P⁵³及EGFR的表达可能与大肠癌的内分泌分化有关     

EFFECTS OF LIMONENE,SALVIA MILTIORRHIZA AND TURMERIC DERIVATIVES ON H-RAS ONCOGENE EXPRESSION AND GAP JUNCTION INTERCELLULAR COMMUNICATION IN HUMAN SOLID TUMOR CELL LINES

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Activating mutations in BRAF characterize a spectrum of pediatric low-grade gliomas

In the present study, DNA from 27 grade I and grade II pediatric gliomas, including ganglioglioma, desmoplastic infantile ganglioglioma, dysembryoplastic neuroepithelial tumor, and pleomorphic xanthoastrocytoma was analyzed using the Illumina 610K Beadchip SNP-based oligonucleotide array. Several consistent abnormalities, including gain of chromosome 7 and loss of 9p21 were observed. Based on our previous studies, in which we demonstrated BRAF mutations in 3 gangliogliomas, 31 tumors were screened for activating mutations in exons 11 and 15 of the BRAF oncogene or a KIAA1549-BRAF fusion product. There were no cases with a KIAA1549-BRAF fusion. A BRAF V600E mutation was detected in 14 of 31 tumors, which was not correlated with any consistent pattern of aberrations detected by the SNP array analysis. Tumors were also screened for mutations in codon 132 in exon 4 of IDH1, exons 2 and 3 of KRAS, and exons 2–9 of TP53. No mutations in KRAS or TP53 were identified in any of the samples, and there was only 1 IDH1 R132H mutation detected among the sample set. BRAF mutations constitute a major genetic alteration in this histologic group of pediatric brain tumors and may serve as a molecular target for biologically based inhibitors.