bcl-2与乳腺癌耐药蛋白基因在弥漫大B细胞淋巴瘤中表达的意义

目的 研究bcl-2和乳腺癌耐药蛋白(BCRP)基因在非霍奇金淋巴瘤(NHL)中的表达及其相关性.方法 对初治弥漫大B细胞淋巴瘤(DLBCL)患者(40例)淋巴结组织液,采用流式细胞术(FCM)及反转录聚合酶链反应(RT-PCR)技术定量检测其BCRP mRNA的表达,同时将患者标本常规石蜡包埋、HE染色和链霉菌素牛物素技术(LSAB)免疫组织化学法标记bcl-2蛋白表达.结果 40例DLBLC患者的bcl-2与BCRP的阳性表达率分别为60.0%(24/40),37.5%(15/40),不同临床分期的DLBCL患者,BCRP阳性表达率差异有统计学意义(x2=6.0606,P<0.05).bcl-2、BCRP表达阳性组有效率低于表达阴性组,差异有统计学意义(x2=5.7618,P<0.05;x2=6.5541,P<0.05);bcl-2和BCRP表达均阳性与均阴性患者的疗效比较,差异无统计学意义(x2=2.0263,P>0.05).结论 BCRP可能在DLBCL的原发多药耐药中发挥重要作用,并有助于化疗疗效的评估及提示疾病转归;bcl-2在DLBCL中的表达对肿瘤恶性程度及预后的判断均有一定意义;联合检测bcl-2和BCRP基因对评价DLBCL预后有较大意义.     

Choi和Hans分型在弥漫大B细胞淋巴瘤预后评价中的意义

目的 探讨Choi和Hans分型在弥漫大B细胞淋巴瘤(DLBCL)预后评价中的意义.方法 收集山西省肿瘤医院病理科有详细随访资料的DLBCL 99例,用免疫组织化学EnVision法检测bcl-2、bel-6、CD10、FOXP1、GCET1、MUM-1的表达情况.根据Choi和Hans两种分类法分别将所有病例分型.其中35例应用荧光原位杂交技术检测bcl-6基因重排情况.结果 按Hans分类法生发中心B细胞(GCB)型21例,非GCB(nonGCB)型78例;按Choi分类法GCB型23例,nonGCB型76例.GCB型生存率明显优于nonGCB型,差异有统计学意义(P=0.000).FOXP1蛋白阳性表达与预后呈负相关(P=0.011),GCET1阳性表达则与预后呈正相关(P=0.027).在35例DLBCL患者中.bcl-6基因重排阳性高发于nonGCB型患者,bcl-6基因重排与bcl-6蛋白的表达没有明显相关性.结论 Choi和Hans两种分类法免疫分型GCB型预后都优于nonGCB型.bcl-6、FOXP1、GCET1的表达与预后有相关性.Choi及Hans分类法对DLBCL的免疫分型、临床预后估计均有应用价值.     

CD20在成年人急性B淋巴细胞白血病中的表达及其临床意义

目的 检测CD20在成年人急性B淋巴细胞白血病(B-ALL)的表达,探讨其与临床特点的相关性.方法 回顾性总结分析96例成年B-ALL患者CD20表达情况,结合其临床特性和治疗转归进行分析.结果 96例成年B-ALL患者中,CD20阳性29例(30.20%),CD20阴性67例(69.79%).CD20阳性组与阴性组男女比分别为1.42∶1和1.79∶1(x2=0.27,P＞0.05),中位年龄分别为28岁与23岁,肝脾及淋巴结浸润比例分别为44.83%和41.38%、40.30%和35.82%,髓系抗原表达比例分别为51.72%与56.72%,Ph染色体和bcr-abl融合基因阳性比例分别为24.14%与28.36%,4周内完全缓解率分别为73.08%与68.85%,差异均无统计学意义(P值均＞0.05).在复发率和3年总体生存率上,CD20阳性组分别为54.55%与14.80%,CD20阴性组分别为29.63%与37.30%,两组间差异有统计学意义(x2=0.42,x2=5.31;P值均＜0.05).结论 CD20在成年人B-ALL表达与临床特点无相关性,但对判断患者的预后有一定的指导意义.     

MUM1/IRF4在滤泡性淋巴瘤中的表达及其临床病理意义

目的 探讨MUM1/IRF4在滤泡性淋巴瘤(FL)中的表达情况及临床病理意义.方法 对96例FL患者标本进行MUM1、CD10、bcl-2、bcl-6、Ki-67免疫组织化学染色,并与患者的临床资料和病理学特征比较.结果 MUM1在96例FL中总的阳性率为59.2%(58/96),其中1～2级组阳性率为36.2%(19/51),3级组阳性率为86.4%(39/45)(x2=24.406,P<0.001).68.9%伴有弥漫成分的FL患者MUM1阳性(x2=8.161,P=0.004).MUM1和CD10的表达呈负相关,83.3%的CD10阴性病例表达MUM1(x1=12.649,P<0.001).MUM1阳性者核分裂和Ki-67标记指数高于MUM1阴性者(t=-3.852、t=-4.610,P<0.001).结论 MUM1可作为FL分型的标志物.MUM1阳性的FL可能为类似非生发中心B细胞分化特征的高度恶性淋巴瘤.     

MTAP、CDKN2A和CDKN2B在弥漫大B细胞淋巴瘤中的表达及其临床意义

目的 研究弥漫大B细胞淋巴瘤(DLBCL)MTAP、CDKN2A和CDKN2B基因的表达及其临床意义.方法 以实时定量聚合酶链反应(PCR)方法检测40例DLBCL及19例淋巴结反应性增生组织中MTAP、CDKN2A和CDKN2B基因的表达情况,结合临床特征进行分析,并进行随访.结果 DLBCL组MTAP、CDKN2A和CDKN2B基因表达水平较淋巴结反应性增生组降低,差异有统计学意义(P值分别为0.024、0.044和0.047);三者表达均与Ann Arbor临床分期相关(P值分别为0.004、0.001和0.027);与患者的性别、年龄、淋巴结外病变累及、ECOG体力评分、骨髓累及、血清乳酸脱氢酶水平均无明显相关(均P＞0.05).其中MTAP与CDKN2A基因表达情况还与B症状(P值分别为0.003和0.028)和国际预后指数(IPI)相关(P值分别为0.001和0.011).此外,生存分析结果显示,MTAP、CDKN2A和CDKN2B基因表达水平与患者总生存期相关(P值分别为0.022、0.019和0.042).结论 MTAP、CDKN2A和CDKN2B基因在DLBCL中呈低水平表达,与疾病进展和患者预后有关,可作为反映其生物学行为和评估患者临床疗效的分子标志物.     

鼻腔自然杀伤/T细胞淋巴瘤放射治疗的疗效和影响因素

目的 回顾分析鼻腔自然杀伤(NK)/T细胞淋巴瘤的放射治疗效果,并分析其预后因素.方法 回顾分析9年间接受放射治疗的62例鼻腔NK/T细胞淋巴瘤的临床资料和疗效,单因素分析采用Kaplan-Meier法,多因素分析用COX比例风险模型.结果 全组中位生存时间69.7个月(95%CI为63.0～78.0个月),3、5年总生存率分别为66.1%和46.8%,远处转移导致治疗失败占61.8%.T淋巴细胞CD3升高组和降低组的中位生存时间分别为72.6个月和39.6个月,两组比较差异有统计学意义(x2=4.9309,P=0.0264).多因素分析表明,修正后国际预后指数(IPI)为0～1(x2=7.5266,P=0.0061)、CD3升高(x2=9.0912,P=0.0266)和治疗结束达到CR(x2=9.0912,P=0.0106)是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.结论 放射治疗鼻腔NK/T细胞淋巴瘤疗效肯定,但远处转移治疗失败率高,全身治疗仍具有重要地位;修正后IPI为0～1、CD3升高、治疗结束达到CR是影响鼻腔NK/T细胞淋巴瘤放疗总生存的有利预后因素.     

NF-κB信号通路的阻断对皮肤鳞癌SCL-1细胞凋亡的影响

目的:利用siRNA技术抑制核因子-kappa B(nuclear factor-kappa B,NF-κB)亚单位p65基因的表达,研究其对p65表达的抑制作用,并探讨其对皮肤鳞癌SCL-1细胞凋亡的影响.方法:将终浓度为50 nmol/L的p65 siR-NA转染皮肤鳞癌SCL-1细胞,通过RT-PCR检测p65 mRNA的表达;利用Western blotting检测p65、bcl-2和bax蛋白表达,利用Caspase-Glo(R)-3/7,8和9检测试剂盒检测caspase-3/9的活性;最后通过流式细胞术检测细胞凋亡.结果:p65 siRNA转染SCL-1细胞后的48 h,p65 mRNA的表达水平最低,与0 h相比,差异有统计学意义(0.23±0.10vs.0.66±0.05,P＜0.05);转染48 h后,p65和bcl-2蛋白表达水平下调,而促凋亡蛋白bax的表达上升,进一步caspase-3/9的活性也显著升高.流式细胞术结果表明,p65 siRNA能明显诱导SCL-1细胞发生凋亡,其早期凋亡的比率为20.28%±1.87%,显著高于未处理组和对照siRNA组(凋亡率分别为9.13%±1.51%和9.37%±1.38%,F=47.532,P＜0.01).结论:p65 siRNA能够阻断皮肤鳞癌细胞中NF-κB信号通路,并下调抑凋亡蛋白bcl-2的表达,上调促凋亡蛋白bax的表达以及提高caspase的活性,提示NF-κB信号通路有望成为皮肤鳞癌基因治疗的分子靶点.     

PTEN、MLL基因在T淋巴母细胞淋巴瘤/白血病的表达及其意义

目的 分析肿瘤抑制基因PTEN、混合系白血病(MLL)基因等在T淋巴母细胞淋巴瘤/白血病(T-LBL/ALL)的表达及意义.方法 选用76例T-LBL/ALl患者淋巴结存档蜡块,应用免疫组织化学EnVision法进行 PTEN标记,用20例反应性增生淋巴结标本作正常对照.并用荧光原位杂交(FISH)技术检测MLL基因所在1 1q23染色体的断裂和扩增情况.结果 76例T-LBL/ALL中,PTEN的表达率为64.47%(49/76),低于淋巴结反应性增生的100%(20/20)(λ2=19.220,P＜0.05).PTEN表达与临床分期、Ki-67、乳酸脱氢酶(LDH)呈负相关(P＜0.05).76例T-LBL/ALL中,MLL基因发生1 1q23染色体断裂13例(17.11%),扩增18例(23.68%).MLL基因断裂组总体生存率(25.0%)低于非断裂组(43.6%)(λ2=11.357,P＜0.05).MLL基因扩增组总体生存率(17.1%)低于非扩增组(42.7%)(λ2=4.533,P＜0.05).结论 抑癌基因PTEN表达降低在T-LBL/ALL的发生发展中可能具有重要作用.MLL基因发生染色体1 1q23断裂和扩增有助于对T-LBL/ALL预后的判断,发生MLL基因断裂或扩增的T-LBL/ALL预后较差,提示MLL基因断裂或扩增可能为T-LBL/ALL的一种分子亚型.     

儿童侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点

目的 分析总结中国儿童各类型侵袭性成熟B细胞淋巴瘤的临床病理学及分子遗传学特点,为其诊断的标准化提供依据.方法 收集97例儿童侵袭性成熟B细胞淋巴瘤石蜡包埋组织标本,包括伯基特淋巴瘤(BL)81例、弥漫大B细胞淋巴瘤(DLBCL)8例、介于BL和DLBCL间的不能分类的B细胞淋巴瘤(BL/DLBCL)8例,利用免疫组织化学技术和间期荧光原位杂交(FISH)技术检测其免疫表型和分子遗传学特征.结果 BL的bcl-2和MUM1的阳性率分别为3%(2/66)和17%(12/71),DLBCL分别为50%(4/8)和63%(5/8),BL/DLBCL分别为50%(4/8)和63%(5/8).BL、DLBCL和BL/DLBCL的Ki-67平均值分别为(93±4.4)%、(83±14.3)%和(80±11.5)%.BL、DLBCL和BL/DLBCL的c-myc基因易位的比例分别为98%(79/81)、38%(3/8)和50%(4/8).38%(3/8)的DLBCL和25%(2/8)的BL/DLBCL存在bcl-6基因的多拷贝,BL与DLBCL之间、BL与BL/DLBCL之间bcl-2、MUM1和Ki-67平均值的差异及c-myc基因易位和bcl-6基因多拷贝的差异均有统计学意义(均P＜0.05).结论 儿童侵袭性成熟B细胞淋巴瘤的诊断和分型需要综合分析形态学、免疫表型和分子遗传学特征.儿童BL/DLBCL可能是DLBCL的一个亚型.CD10+、bcl-6+、bcl-2-、Ki-67＞90%、伴有IGH/c-myc重排、不伴有bcl-2和bcl-6重排时,支持BL的诊断;bcl-2+、Ki-67为50%～90%,同时伴有bcl-6基因的多拷贝时,支持DLBCL或BL/DLBCL的诊断.     

荧光原位杂交检测乳腺癌人表皮生长因子受体2基因扩增及与临床病理特征的关系

目的:探讨荧光原位杂交法(fluorescence in situ hybridization,HSH)及免疫组织化学法(immunohistochemistry,IHC)检测乳腺癌人表皮生长因子受体2(human epidermal growth factor receptor2,HER-2)的一致性,及HER-2基因扩增与乳腺癌临床病理特征的关系.方法:对北京大学第三医院病理科2008年1月至10月的乳腺浸润性导管癌病例中选取的41例进行HER-2基因扩增的FISH检测和蛋白表达的IHC检测,并对HER-2基因扩增与雌激素受体(estrogen receptor,ER)、组织学分级、癌周脉管内癌栓、腋窝淋巴结转移的关系进行统计学分析.结果:41例乳腺浸润性导管癌中,HER-2基因扩增患者15例,为IHC检测+++者8例,++者6例,+者1例,阴性者0例,分别占IHC+++、++、+及阴性者病例总数的88.89%(8/9)、42.68%(6/14)、8.33%(1/12)及0%(0/6).HER-2基因扩增率在不同组织学分级的乳腺浸润性导管癌中差异无统计学意义(P=0.095).HER-2基因扩增率在ER阴性及弱阳性(+)组高于ER强阳性(++或+++)组(P=0.018),可见脉管内癌栓组高于未见脉管内癌栓组(P=0.000),同侧腋窝淋巴结有转移组高于腋窝淋巴结无转移组(P=0.025).结论:FISH技术可较稳定地应用于乳腺癌HER-2基因扩增的检测,IHC++的患者需进一步行FISH检测;HER-2基因扩增与ER表达呈负相关,与癌周脉管内癌栓、腋窝淋巴结转移呈正相关.     

p53 alterations are associated with improved prognosis in distal colonic carcinomas

Alterations of the p53 gene and the p53 protein are common in a wide spectrum of human malignancies. In several tumor types, p53 gene mutation and/or p53 protein overexpression correlate with a more clinically aggressive phenotype as judged by worse patient survival. This has not been clearly demonstrated to be the case in colorectal cancer. Herein, we report results of the prognostic significance of p53 protein accumulation and gene mutation in a large series of colorectal cancers (n = 541) with long patient follow-up (mean, 87 months). The large majority of patients (95%) received no postoperative systemic adjuvant therapy. The incidence of p53 accumulation detected by immunohistochemistry with the monoclonal antibody DO-7 was 30%, whereas the incidence of p53 gene mutation in exons 5-8 detected using PCR-single strand conformation polymorphism was 36%. Accumulation of p53 protein was associated with improved patient survival independent of tumor stage or grade (hazard ratio, 0.66; 95% confidence interval, 0.47-0.93; P = 0.017). A marked difference was observed depending on the location of the tumor: tumors originating in the distal colon showed a strong association between the presence of p53 accumulation and improved patient survival (P = 0.003), but this was not the case for those located in the proximal colon. Dukes' stage C tumors, but not stage B, also showed an association between p53 accumulation and better outcome (P = 0.013). Mutation of the p53 gene was associated with a trend toward improved survival, particularly in the distal tumors. Our results demonstrate that in some tumor types, the presence of p53 abnormalities can correlate with better prognosis.     

Osmolyte contents of cultured astrocytes grown in hypoosmotic medium

The prognostic value of p53 protein overexpression was investigated in a large series of early stage endometrial carcinomas with long follow-up (n=179, median follow-up 147 months). P53 overexpression was detected in 10 cases (5.6%). At the end of the study period, 30% (3/10) of patients with p53 protein overexpression had died of their disease compared to 6.5% (11/169) of those without overexpression. Multivariate analysis revealed that only myometrial invasion (RR 2. 1; 95% CI=1.2-3.6; P=0.001) and p53 overexpression (RR 9.5; 95% CI=2. 5-36.8; P=0.007) were independent predictors of survival. These results suggest that immunohistochemical evaluation of p53 protein overexpression provides strong prognostic information for the outcome of endometrial carcinoma patients with early stage disease.     

Aprotinin inhibits plasmin-induced platelet activation during cardiopulmonary bypass

PURPOSE: We correlated the expression of bcl-2 with accumulation of p53 protein in bone marrow metastases from patients with androgen independent prostate cancer and a history of hormonal ablation therapy. These results were correlated with clinical parameters, including the extent of bone marrow metastases and patient survival. MATERIALS AND METHODS: All 43 patients studied had evidence of prostate cancer progression following androgen deprivation therapy and histologically confirmed bone marrow metastases. Decalcified tissue sections were used for immunohistochemical evaluation of bcl-2 protein and p53 protein accumulation. RESULTS: We previously established that p53 protein accumulation as detected by immunohistochemistry is a reliable indicator of p53 gene mutation in prostate cancer. Immunoreactivity was demonstrated for p53 protein in 22 of 43 cases and for bcl-2 protein in 14. A total of 28 cases (65%) exhibited immunohistochemical evidence of p53 and/or bcl-2 expression, and 15 (35%) were negative for p53 and bcl-2. The expression of bcl-2 and accumulation of p53 were independent events (p < 0.01). The expression of bcl-2 or accumulation of p53 protein in prostate cancer metastases did not significantly influence patient survival or the extent of metastatic disease. CONCLUSIONS: The presence or absence of p53 protein accumulation and/or bcl-2 expression did not correlate with tumor burden or patient survival in stage D androgen independent prostate cancer bone marrow metastases. The expression of bcl-2 protein occurs independently of and is inversely correlated with p53 mutations in advanced prostate cancer.     

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.     

p53 status has no prognostic significance in glioblastomas treated with radiotherapy

Mutation of the tumor suppressor gene TP53 and accumulation of the p53 protein are common events in the range of cerebral astrocytic tumors, including glioblastomas, but it is uncertain whether these events are associated with prognosis. Evidence suggests that the response of various tumors to radiotherapy may be influenced by the status of p53 which is involved in control of the cell cycle and apoptosis. This study tests the hypothesis that p53 governs survival in patients (n = 62) with glioblastomas who have received radiotherapy. Analysis of TP53 and p53 immunohistochemistry were undertaken using standard methods. TP53 mutations were present in 27% tumors, while 50% were p53-immunopositive (LI > 3%). A strong correlation (p < 0.0001) was found between a high p53 LI (> 50%) and the presence of a mutation, but p53 status at the level of gene or protein was unrelated to survival. Radiation-induced apoptosis that is independent of p53, and the presence in glioblastomas of genetic abnormalities that are also involved in the cellular response to radiation, such as deletions and mutations of pRb, are possible explanations of this result.     

Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma

PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.     

Prognostic value of bcl-2 oncoprotein expression in stage II colon carcinoma

The bcl-2 proto-oncogene encodes a Mr 25,000 protein that has been shown to prevent apoptosis or programmed cell death. The bcl-2 protein is detectable in basal cells of normal colonic epithelium, and an altered topographic distribution of this protein is found in colonic neoplasms. However, the clinical significance of abnormal bcl-2 expression in colon carcinomas remains unknown. We examined the prognostic value of the bcl-2 protein in TNM stage II colon carcinomas and its relationship to DNA ploidy, cell proliferation indices, p53 expression, and clinicopathological features. We analyzed 119 resected and otherwise untreated, paraffin-embedded stage II colon carcinomas for bcl-2 and p53 protein expression using immunohistochemistry. DNA ploidy and proliferative index (% S-phase + % G2-M) were determined by flow cytometry, and tumor grade and vascular microinvasion were assessed on histological sections. Cytoplasmic expression of the bcl-2 protein was detected in 72 (66%) of 110 carcinomas, and a high level of expression was significantly correlated with diploid DNA content (P = 0.02) and low proliferative activity (P = 0.005). bcl-2 was not associated with nuclear p53 expression. In a univariate analysis, a higher fraction of bcl-2-positive tumor cells was associated with better relapse-free survival (P = 0.02) and overall survival (P = 0.05) rates. Moreover, a high level of bcl-2 expression was an independent predictor of better relapse-free survival (P = 0.04), but not overall survival (P = 0.14), after adjustment for other variables, including proliferative index, DNA ploidy, and race. In conclusion, bcl-2 overexpression is associated with favorable prognostic features and may predict clinical outcome in stage II colon carcinomas.     

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.     

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.