Prognostic relevance of proliferating cell nuclear antigen and p53 expression in non-small cell lung cancer.

Prognostic value of p53 and PCNA expression in non-small cell lung cancer (NSCLC) remains controversial. In this study we determined the relevance of these abnormalities in terms of overall survival and disease-free survival in 95 NSCLC patients who underwent curative pulmonary resection. Expression of p53 was found in 44 samples (45%), expression of PCNA-in 79 samples (83%), and expression of both markers-in 35 samples (36%). There was no relationship between expression of either protein and major clinicopathological characteristics. Median survival for patients with and without p53 expression was 36 and 33 months, respectively and 5-year survival probability-29 and 37%, respectively (P=0.73). Median survival for patients with and without PCNA expression was 36 and 27 months, respectively and 5-year survival probability-35 and 25%, respectively (P=0.60). There was no significant difference in overall survival between particular groups of patients with tumors carrying four possible p53/PCNA phenotypes. In multivariate analysis including patient age, sex, tumor stage, tumor type and differentiation, p53 and PCNA expression, the only variable important for survival was stage of disease. These results suggest the lack of prognostic relevance of p53 and PCNA expression in surgically treated NSCLC patients.     

E-cadherin、CD44v6和PCNA在非小细胞肺癌组织中的表达及意义

背景与目的:上皮钙依赖粘附蛋白(E-cadherin,E-cad)、CD44v6和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在恶性肿瘤侵袭与转移中发挥重要作用。本研究旨在探讨E-cad、CD44v6和PCNA在非小细胞肺癌(non-small cell lung cancer,NSCLC)及癌旁组织中的表达与NSCLC的侵袭、转移及预后的关系。方法:应用免疫组化EnVision法检测86例NSCLC组织及40例癌旁组织中E-cad、CD44v6和PCNA的表达,并分析与NSCLC的侵袭、转移及预后的关系。结果:E-cad在肺癌组织中的表达率为53.5%(46/86),显著低于癌旁组织(80.0%)(P<0.05),且与NSCLC的分化程度、淋巴结转移和TNM分期有关(P<0.05);CD44v6在肺癌组织中的表达率为44.2%(38/86),在癌旁组织中无表达,且在鳞癌中的表达率(54.0%)显著高于腺癌(30.6%)(P<0.05),并且与淋巴结转移和TNM分期有关(P<0.05);PCNA在肺癌组织中的表达率为48.8%(42/86),在癌旁组织中无表达,且在淋巴结转移组与未转移组间的表达差异有统计学意义(P<0.05)。E-cad与PCNA的表达呈显著性负相关(r=-0.554,P<0.05),而CD44v6与PCNA的表达呈显著性正相关(r=0.688,P<0.05)。单因素生存分析显示E-cad、CD44v6及PCNA的表达与NSCLC患者预后有关。Cox比例风险模型进行多因素生存分析显示;E-cad与临床分期是有意义的预后指标(P<0.05)。结论:E-cad、CD44v6及PCNA的表达与NSCLC的侵袭和转移相关。在NSCLC中联合检测三者的表达对判断预后有参考价值。     

非小细胞肺癌中增殖细胞核抗原的表达及其意义

目的探讨非小细胞肺癌（ＮＳＣＬＣ）中增殖细胞核抗原（ＰＣＮＡ）的表达及与一些临床指标的相关性。方法利用免疫组化ＡＢＣ法回顾性分析１９６４年１月～１９９４年１２月间中国医学科学院肿瘤医院开胸探查术后或纤维支气管镜活检术后单纯放射治疗的９５例非小细胞肺癌的ＰＣＮＡ表达情况。结果全部病例均有ＰＣＮＡ表达,ＰＣＮＡ指数（ＰＩ）值平均为０．５２３,统计分析ＰＩ值与ＮＳＣＬＣ原发灶所在部位、分型、分化、分期、放射敏感性及预后均无相关性,（Ｐ＞０．０５）,但在分期分析中,有随分期愈晚,ＰＩ值逐渐增加的趋势。结论ＰＣＮＡ表达与非小细胞肺癌原发部位、分型、放射敏感性及预后无明显相关性;与分期、分化的相关性有待继续探讨。     

Angiostatin expression in non-small cell lung cancer.

Angiostatin, a potent inhibitor of angiogenesis, tumor growth, and metastasis, was examined in a panel of human lung cancer cell lines with Western blot analysis and in 143 primary non-small cell lung carcinomas with immunohistochemistry. Thirty-four of 143 cases (24%) stained positively. Patients with angiostatin-positive tumors survived longer (146 weeks) than patients with angiostatin-negative tumors (77 weeks; log-rank test: P = 0.07; rank-sum test: P = 0.02). To determine whether combining stimulating and inhibiting factors might improve the prognostic capability, both angiostatin and vascular endothelial growth factor (VEGF) were analyzed together with respect to patient survival. The median survival time of patients with angiostatin-positive/VEGF-negative carcinomas was 184 weeks, whereas the median survival time of patients with angiostatin-negative/VEGF-positive tumors was only 52 weeks. The angiostatin-positive tumors exhibited an increased incidence of apoptosis and a reduced capability to be transplanted into nude mice, but these differences did not reach or were only of borderline statistical significance.     

P-糖蛋白、bcl-2蛋白和增殖细胞核抗原在肺癌组织中的表达及意义

目的：研究Ｐ－糖蛋白（Ｐ－ｇｌｙｃｏｐｒｏｔｅｉｎ,Ｐ－ｇｐ）的表达与ｂｃｌ－２蛋白和增殖细胞核抗原（ｐｒｏｌｏｆｅｒａｔｉｎｇ－ｃｅｌｌｎｕｃｌｅａｒ ａｎｔｉｇｅｎ,ＰＣＮＡ）表达的关系及意义。方法：用特异性鼠抗人单克隆抗体,用ＳＰ免疫组织化学方法检测石蜡包埋的肺癌标本中Ｐ－ｇｐ,ｂｃｌ－２蛋白和ＰＣＮＡ的表达,结果：在小细胞肺癌（ｓａｍｌｌ ｃｅｌｌ ｌｕｎｇ ｃａｎｃｅｒ,ＳＣＬＣ）中,Ｐ     

增殖细胞核抗原与AgNOR检测在前列腺癌临床中的意义

目的研究前列腺癌中增殖细胞核抗原（ＰＣＮＡ）表达及ＡｇＮＯＲ计数的意义。方法应用免疫组织化学方法和银染色技术检测前列腺癌和良性前列腺增生组织中ＰＣＮＡ表达和ＡｇＮＯＲ计数。结果ＰＣＮＡ增殖指数与ＡｇＮＯＲ计数在癌组织中均明显高于良性前列腺增生组织（Ｐ均＜０．００１）,且两者均与肿瘤组织学分级和预后有密切关系（Ｐ均＜０．０１和Ｐ均＜０．００１）;前列腺癌ＰＣＮＡ增殖指数与ＡｇＮＯＲ计数间存在非常显著的正相关（Ｐ＜０．０１）。结论ＰＣＮＡ增殖指数和ＡｇＮＯＲ计数结合分析,在鉴别前列腺良恶性病变和判断前列腺癌的恶性程度及预测患者预后方面具有十分重要的意义。     

Proliferative potential of meningiomas evaluated by proliferating cell nuclear antigen expression

Meningiomas are principally benign in nature. Some meningiomas, however, grow fast or recur even after total removal. The biological behavior of meningiomas often can not be predicted from conventional histopathological studies. A monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used to investigate the usefulness of the PCNA index as a parameter to estimate the proliferative activity of meningiomas. Fifty-two meningiomas were examined. The mean PCNA index of recurrent meningiomas (3.37±0.92%) was significantly higher than that of non-recurrent meningiomas (1.12±0.51%) (p <0.005). The PCNA indices of recurrent cases were all higher than 2.0%. A semilog linear regression analysis between tumor doubling time and PCNA index showed a significant correlation (r=0.90, p < 0.05). An inverse linear correlation between PCNA index and interval to recurrence was observed (r=0.62, p < 0.05). A good linear correlation was also shown between PCNA index and BUdR labeling index (r = 0.88, p < 0.01). The results of this study suggest that, providing the methods of tissue processing, immunostaining and counting of positive nuclei are unified, the PCNA index is a useful parameter for estimating the biological behavior of meningiomas.     

流式细胞术检测肺癌组织HLA-ABC的意义

检测HLA—ABC（经典人类白细胞抗原Ⅰ类抗原）在肺癌组织的表达可为肺癌的免疫治疗提供指导。恶性转化的肿瘤细胞可通过不同的机制使其表面的HLA—ABC的表达缺失或下降，从而逃避机体的免疫监视。针对不同的缺失类型，其免疫治疗方案不同。如TAP缺陷造成的HLA—ABC整个分子缺失，可选择性使用某些细胞因子；而HLA单倍型缺失，染色体异常，则用基因治疗。非小细胞肺癌HLA—ABC表达低下在大多数研究中得到证实，但多采用免疫组化方法进行检测，费时费力且检测结果不一，同时对HLA—ABC表达低下的临床意义也存在着争议。针对以上问题，本实验采用流式细胞术（FCM）检测非小细胞肺癌（NSCLC）组织HLA—ABC的表达，评价其对肺癌免疫治疗方案选择的意义。     

独一味胶囊对大鼠动脉管壁增殖细胞核抗原表达的影响

目的：观察藏药独一味胶囊对经皮冠状动脉成形术（percutaneous transluminal coronary angioplasty,PTCA）大鼠动脉管壁增殖细胞核抗原（proliferating cell nuclearantigen,PCNA）表达的影响。方法：Wistar大鼠40只随机分为PTCA模型组（同时设右侧相同部位的颈总动脉为正常对照）、独一味胶囊0.50、1.25、2.50g/kg组、阳性对照组（丹参片1.0g/kg）,共5组,每组8只。各组动物灌胃给予相应药物第5天后行PTCA术,建立颈动脉球囊损伤模型;PTCA术后继续给予相应药物28 d后取损伤节段颈总动脉,常规病理切片后行免疫组织化学检测,测定PCNA的表达。结果：正常对照管壁PCNA表达极少或无表达。模型组动脉内膜PCNA表达的阳性率为33.71%;独一味胶囊0.50、1.25、2.50g/kg组动脉内膜PCNA阳性率依次为28.00%、27.83%、27.33%,与模型组比较均显著降低（P〈0.05或P〈0.01）。结论：独一味胶囊可显著抑制PCNA的表达,可能是预防大鼠颈动脉损伤后再狭窄的机制之一。     

胶质瘤中朊病毒蛋白和增殖细胞核抗原表达的相关性

目的研究胶质瘤中朊病毒蛋白(PrP)表达的生物学意义.方法采用免疫组织化学和图像分析技术,对45例胶质瘤中PrP和增殖细胞核抗原(PCNA)的表达进行定量研究和相关性分析.结果PrP和PCNA在各级胶质瘤中均有不同程度的表达,Ⅰ-Ⅱ级、Ⅲ级和Ⅳ级阳性细胞吸光度分别为10±3.7、21±6.8、24±6.5和12±4.0、29±7.2、34±7.9,除Ⅲ级与Ⅳ间无显著性差异外(P＞0.05),Ⅰ-Ⅱ级、Ⅲ级和Ⅳ级阳性细胞吸光度分别为10±3.7、21±6.8、24±6.5和12±4.0、29±7.2、34±7.9,除Ⅲ级与Ⅳ级间无显著性差异外(P＞0.05),Ⅰ-Ⅱ级与Ⅲ级、Ⅳ级间比较均具有显著性差异(P＜0.05),PrP表达的程度与胶质瘤的分化程度呈负相关,与PCNA的表达呈正相关(r=0.73、P＜0.001).结论PrP在判断胶质瘤组织学分级和预后上有较重要的使用价值.     

非小细胞肺癌患者外周血粘附分子表达的临床意义

目的 :探讨非小细胞肺癌患者外周血粘附分子CD4 4和CD6 2P的表达特征及其临床意义。方法 :应用流式细胞仪对 5 5例肺癌患者外周血CD4 4和CD6 2P表达进行荧光免疫检测 ,并与正常对照组 (n =30 )进行对比研究。结果 :5 5例肺癌患者外周血中CD4 4和CD6 2P表达明显高于正常对照组 (P <0 0 1)。Ⅲ期、Ⅳ期和Ⅰ期、Ⅱ期之间CD4 4和CD6 2P表达比较 ,有显著性差异 (P <0 0 1)。CD4 4和CD6 2P表达与肺癌组织学分级有明显相关性 (P <0 0 1)。结论 :应用流式细胞仪检测CD4 4和CD6 2P的表达水平可作为肺癌转移和预后的指标     

微血管密度及增殖细胞核抗原表达与宫颈癌放射敏感性的关系初探

目的探讨增殖细胞核抗原(PCNA)和肿瘤间质微血管密度(MVD)与宫颈癌放射敏感性的关系.方法采用回顾性研究的方法,运用LSAB免疫组织化学染色技术检测80例单纯放射治疗并随访5年以上宫颈癌患者的PCNA指数和MVD值.结果 80例宫颈癌患者均有不同程度的PCNA表达,PCNA指数分布在0.243～0.913之间,平均为0.522;微血管计数为(51.8±11.5)条,实际范围21～72条.结论 PCNA的表达和MVD值与宫颈癌的放射敏感性有关,为寻找能预测宫颈癌放射敏感性的肿瘤标志物,指导临床治疗方案的选择提供了初步的实验依据.     

Prognostic-significance of proliferating cell nuclear antigen (pcna) in adenocarcinoma of the lung

The aim of the study was to investigate the prognostic value of the proliferating cell nuclear antigen (PCNA) expression in non-small cell lung carcinomas (NSCLC). Two hundred and sixteen patients with previously untreated NSCLC entered into this investigation. For assessment of PCNA expression the streptavidin-biotinylated peroxidase complex method was performed using imnuunohistochemistry and Mab PC10. The tumors were scored for the percentage of PCNA-positive cells (low proliferative activity less than or equal to 25%; high proliferative activity >25%). Univariate analyses of all patients showed a trend that those with high proliferating tumors had shorter survival times than those with lower proliferating tumors. Similar results were obtained when the analysis was restricted to squamous cell carcinomas. Patients with adenocarcinomas and with high proliferating tumors had significantly shorter survival times than those with low proliferating tumors (p=0.028). No correlation was found between extent of tumors or metastasis and expression of PCNA. The multivariate analysis including age, sex, extent of tumors and metastasis as well as PCNA revealed a highly significant influence of extent of tumors (p=0.007) and metastasis (p=0.003) whereas all other factors including PCNA were of no significant influence.     

Preoperative lymphocyte count is an independent prognostic factor in node-negative non-small cell lung cancer

A number of prognostic factors have been reported in non-small cell lung cancer (NSCLC). Although lymph node metastasis is the most poorly predictive value in completely resected NSCLC, a significant number of patients have a fatal recurrence even in node-negative curative NSCLC. Recently inflammatory response has been shown as a predictive value in NSCLC. Neutrophils and lymphocytes play an important role in cancer immune response. In this study, we retrospectively examined the impact of preoperative peripheral neutrophil and lymphocyte counts on survival, and investigated the relationships of these factors to clinicopathological factors in node-negative NSCLC. A total 237 patients were evaluated. When the cut-off value of neutrophil count was 4500 mm⁻³ with a maximum log-rank statistical value, overall 5-year survival rates were 79.7% for the low-neutrophil-count group and 69.5% for the high-neutrophil-count group (P = 0.04). When the cut-off value of lymphocyte count was 1900 mm⁻³ with a maximum log-rank statistical value, overall survival rates were 67.9% for the low-lymphocyte group and 87.7% for the high-lymphocyte group (P < 0.001). High-neutrophil-counts were associated with tumor size (P = 0.002) and pleural invasion (P < 0.001). Low-lymphocyte-counts were correlated with vascular invasion (P = 0.018) and recurrence of NSCLC (P = 0.01). Multivariate analysis showed that the lymphocyte count was an independent prognostic factor (hazard ratio: 3.842; 95% confidence interval: 1.827-8.078; P < 0.001), but the neutrophil count was not (P = 0.185). We conclude that a peripheral lymphocyte count, which is associated with vascular invasion, is an independent prognostic factor in node-negative NCSLC.     

增殖细胞核抗原和毛细血管间距与宫颈癌放射敏感性的关系

目的：探讨肿瘤内毛细管间距（ICD）和增殖细胞核抗原（PCNA）与宫颈癌放射敏感性的关系。方法：采用回顾性研究的方法,运用免疫组织化学技术和计算机图像分析方法测定112例单纯放射治疗并随访5披颈癌患者的PCNA表达和ICD值。结果：本组所有病例均有PCNA有达,PCNA指数分布在0．241－0．903之间,平均为0．542;WFHGD渗58．47－243．62μm之间,平均为180．42μm。结论：本研究表明PCNA的表达和ICD值与宫颈癌的放射敏感性前有关,为寻找能预测宫颈癌放射敏感性的肿瘤标志物、指导临床治疗方案的选择提供了初步的实验依据。     

增殖细胞核抗原对乳腺癌预后的意义

用免疫组化法检测了５５例乳腺癌和１３例乳腺良性病变的增殖细胞抗原，结果ＰＣＮＡ增殖指数在乳腺癌为０％－８１％，在乳腺良性病变为０％－６８％，乳腺癌中也腺良性病变。在乳腺癌中ＰＣＮＡ表达与组织学分级，淋巴结转移及组织蛋白酶Ｄ间质表达呈正相关，与ＣａｔｈＤ实质表达，无病生存期及总生存期呈负相关。     

The relationship between the expression of proliferating cell nuclear antigen and clinicopathological variables of gastric-cancer

A monoclonal antibody against proliferating cell nuclear antigen (PCNA), PC10, was applied to 96 gastrectomy specimens obtained from patients with gastric cancer. Resected tissue was routinely processed and stained immunohistochemically with PC10. One thousand tumor cells were counted and the ratio of the number of stained cells to total tumor cells was calculated as the PCNA index, which ranged from 13.8% to 88.8% with a mean of 61.4%. Although the PCNA index did not correlate with pathological variables including histological type, lymph node metastasis, growth pattern and venous invasion, it was significantly lower in mucosal carcinomas compared with submucosal and advanced carcinomas.     

Osteopontin expression and prognostic significance in non-small cell lung cancer.

PURPOSE: The survival rate of non-small cell lung cancer patients is very low, and knowledge of predictors of outcome is inadequate. To improve the curability of lung cancer, we need to identify new specific molecules involved in tumorigenesis and progression. The purpose of this study was to better define the role of osteopontin in non-small cell lung cancer biology by determining its prognostic significance. EXPERIMENTAL DESIGN: Osteopontin expression was evaluated by immunohistochemistry, as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide series of patients with stage I-IIIA non-small cell lung cancer (207 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumors with low (<20%) from tumors with high (> or =20%) osteopontin expression. RESULTS: Taking the series of patients as a whole (207 cases), osteopontin expression was associated with neither overall survival (P = 0.14) nor disease-free survival (P = 0.074). However, among patients with at least 6 years of follow-up (163 cases), 6-year overall survival and disease-free survival were significantly reduced if osteopontin expression was high (P = 0.0085 for overall survival, P = 0.0023 for disease-free survival). Moreover, a statistically significant correlation between high levels of osteopontin and shorter overall survival (P = 0.034) and disease-free survival (P = 0.011) in patients with stage I tumors (136 cases) was shown. CONCLUSIONS: Our results support the hypothesis of an association between high osteopontin expression and poor survival of patients with stage I non-small cell lung cancer, suggesting that osteopontin could be a candidate target for cancer therapy.