The short-term efficacy of icotinib on the treatment of advanced non-small-cell lung cancer简

Objective： The aim of the study was, （1） to observe the short-term efficacy and adverse reactions of icotinib hydrochloride on the treatment of advanced non-small cell lung cancer （NSCLC）; （2） to explore whether there is difference in the efficacy of icotinib hydrochloride among the subgroups of sex, age, smoking history, classification of CEA, histological type, multi-line treatment and PS score. Methods： The study was conducted to collect 138 patients taking icotinib hydrochloride with advanced non-small cell lung cancer in hospitals of Dalian （China） from September 1st 2011 to June 14th 2012. All patients had taken icotinib hydrochloride （125 mg three times a day） until the disease was progressed or the adverse reactions could not be tolerated. During the period of taking it, other anti-tumor treatments were forbidden. We observed the symptoms, such as cough, short breath, hemoptysis, pain. The objective efficacy was evaluated by RECIST criteria, and the adverse reactions related to the treatment was assessed on the basis of NCl-CTC 3.0. Results： Of all patients, CR was 1 （0.7%）, PR was 59 （42.8%）, SD was 37 （26.8%）, PD was 41 （29.7%）. And ORR was 43.5% （60/138）, DCR 70.3% （97/138）. The DCR of females was 83.5% （71/85） versus 49.1% （26/53） of males. The difference of ORR and DCR between the two subgroups had statistical significance （X2 = 8.065, P = 0.05; X2 = 18.577, P = 0.000）. The difference of ORR and DCR between the subgroups of patients after or before 70 years old had no statistical significance. The difference of ORR and DCR between the subgroups of smoking and non-smoking had statistical significance （X2 = 8.492; X2 = 13.602）. The difference of ORR and DCR between the CEA subgroups had statistical significance （X2 = 14.141; X2 = 14.160）, showed 81 patients with abnormal CEA before the treatment with ORR 56.8.0% （46/81）, DCR 81.5% （66/81）; 57 patients of normal CEA before the treatment with ORR 24.6% （14/57）, DCR 52.6% （30/57）. The 36 patients （26.1%） using icotinib hydrochloride as the first-line treatment, 78 patients （56.5%） using icotinib hydrochloride as the second-line, 20 patients （14.5%） using icotinib hydrochloride as the third-line, and 4 patients （2.9%） with tyrosine kinase inhibitor （TKI） resistance, there was statistical difference of DCR among the multi-groups above （~2 = 11.734, P = 0.008）. ORR was 31.1% （14/45） versus DCR 53.3% （24/45） in 45 patients with PS 3-4 points, and ORR was 49.4% （46/93） versus DCR 78.5% （73/93） in 93 patients with PS 0-2 points, and there was statistical difference （X2 = 4.156; X2 = 9.149）. The main adverse reactions were rash （26.8%）, diarrhea （13.8%）, mild liver function abnormal （10.9%）. Conclusion： The short-term efficacy of icotinib hydrochloride on the treatment of advanced NSCLC is positive, and the relevant adverse reactions are mild. The efficacy is better when the patient is female, non-smoker, treated as first-line, with higher CEA before treatment and lower PS scores.     

胰岛素样生长因子1在非小细胞肺癌中的表达及其预后价值

目的：研究胰岛素样生长因子（IGF1）在非小细胞肺癌组织中的表达，探讨其与肺癌临床病理学特征和生存间的关系。方法：采用免疫组织化学和免疫印迹技术检测IGF1在29例肺鳞癌和22例肺腺癌（25例含癌旁肺组织）及12例良性肺病变组织中的表达。采用x^2检验检测其与临床病理学特征的关系，Log-rank检验IGF1表达与生存时间的关系，Gox模型作单因素和多因素预后分析。结果：IGF1在肺癌中的阳性表达率为51%（26/51），表达率和强度显著高于良性肺组织（P分别为0.0143和0.0039）。晚期肺癌（Ⅲ＋Ⅳ）IGF1阳性表达率和强度显著高于早期肺癌（Ⅰ＋Ⅱ）（P分别为0.0032和0.0094）。IGF1在伴有局部淋巴结转移肺癌组织 的阳性表达率显著高于无淋巴结转移肺癌组织中的表达（P=0.0074）。IGF1阳性表达患者的中位生存时间显著短于IGF1阴性者（12个月比35个月，P=0.0001），Cox模型分析表明，IGF1表达是非小细胞肺癌的独立预后因素。结论：本研究结果提示，IGF1过表达的非小细胞肺癌的发生和发展中可能起重要作用，检测IGF1表达有望成分判断非小细胞肺癌预后的参考指标之一。     

局限期小细胞肺癌增强CT与Ki-67抗原表达的对照研究

目的 局限期小细胞肺癌(limited-stage small cell lung cancer,LS-SCLC)是指SCLC局限于同侧胸腔、纵隔和锁骨上,无明显的上腔静脉压迫、声带麻痹及胸腔积液.Ki-67抗原可反映肿瘤细胞的增殖活性,间接提示肿瘤恶性程度.本研究旨在探讨LS-SCLC增强CT与Ki 67抗原表达水平的关系.方法 回顾性分析山东大学附属山东省肿瘤医院2014-07-01-2015-09-01经穿刺活检或手术病理确诊的43例LS-SCLC患者的临床资料.患者均于穿刺活检或手术前行平扫及增强CT检查.穿刺或手术标本作免疫组化Ki-67抗原染色,测定肿瘤细胞阳性百分率,即Ki-67标记指数(Ki-67 labeling index,Ki-67 LI).分析CT征象、平扫及增强后CT值与Ki-67 LI值的关系.结果 43例LS-SCLC患者的Ki-67 LI值为40％～90％,均值为(67.86±16.83)％.其瘤体最大径≥30 mm、边缘清楚和无毛刺征Ki-67 LI比瘤体最大径＜30 mm、边缘毛糙和有毛刺征高,P值分别为0.002、0.033和0.023.平扫、Ⅰ和Ⅱ期增强后CT值与Ki-67 LI值呈显著正相关性,P值分别＜0.001、0.003和0.038.Ki-67 LI值在有无坏死、空气支气管征、分叶征和淋巴结转移间差异无统计学意义,P＞0.05.结论 LS-SCLC的增强CT与Ki-67抗原表达水平相关,可间接反应肿瘤的增殖活性,评估恶性程度.     

Association of Ki-67, p53, and bcl-2 expression of the primary non-small-cell lung cancer lesion with brain metastatic lesion

: The study was conducted to determine whether immunohistochemical analysis of Ki-67, p53, and bcl-2 in patients with non-small-cell lung cancer is associated with a higher rate of brain metastases and whether the intrapatient expression of these biomarkers (in the primary tumors vs. brain lesions) is similar.

: At the M. D. Anderson Cancer Center, tumors from 29 case patients with primary lung tumor and brain metastasis and 29 control patients with primary lung tumor but no brain metastasis were resected and examined for immunohistochemical expression. Ki-67, p53, and bcl-2 were analyzed in resected primary lung, lymph node, and metastatic brain tumors. Each control patient was matched by age, gender, and histology to a patient with brain metastasis.

: No significant differences in patient survival characteristics were detected between the case group and control group. Also, difference in patient outcome between the two groups was not generally predicted by biomarker analysis. However, when the groups were combined, the biomarker analysis was predictive for certain patient outcome end points. Using median values as cutoff points between low and high expression of biomarkers, it was observed that high expression of Ki-67 (>40%) in lung primaries was associated with poorer disease-free survival (p = 0.04), whereas low expression of p53 in lung primaries was associated with poorer overall survival (p = 0.04), and these patients had a higher rate of nonbrain distant metastases (p = 0.02). The patients with brain metastases were particularly prone to developing nonbrain distant metastases if the percentage of p53-positive cells in brain metastases was low (p = 0.01). There was a positive correlation in the expression of Ki-67 (p = 0.02)(r² = 0.1608), as well as p53 (p < 0.001) (r² = 0.7380), between lung primaries and brain metastases. Compared to Ki-67 and p53, bcl-2 was the least predictive.

: Differences in biomarker expression between the case and control groups did not serve as significant predictors of brain metastasis or patient survival. There was a strong correlation between lung primary biomarker expression and brain metastasis expression for Ki-67 and p53. Univariate analysis showed that low p53 and high Ki-67 expression predicted poor prognosis. This study shows that there may be a strong correlation between biomarker expression in non-small-cell lung cancer primary tumors and their brain metastases.     

Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

Objective： The purpose of the study was to assess prognostic factors to predict overall survival （OS） and progres- sion-free survival （PFS） in non-small-cell lung cancer （NSCLC） with brain metastasis （BM）. Methods： From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy （WBRT） combined with tyrosine kinase inhibitor （TKIs）. The efficacy and adverse reaction were evaluated after treatment. Results： In terms of intracranial lesions, the objective response rate （ORR） and the disease control rate （DCR） were 22.6% and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3% and 93.5%, respectively. The median time to progression-free survival （PFS） was 298 days （95% CI： 258.624-337.376 days）, whereas in the epidermal growth factor receptor （EGFR） mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate （RR） than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxicities were rash and diarrhea, but all were well-tolerated. Conclusion： EGFR-mutations is the independent prognostic factors affecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be effective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.     

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.     

Prognostic significance of osteopontin expression in early-stage non-small-cell lung cancer

Osteopontin (OPN) is a multifunctional protein, which has recently been shown to be linked to tumorigenesis, progression and metastasis in different malignancies. Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few predictors of outcome, the purpose of this study was to evaluate if OPN might be involved in NSCLC's biology and therefore represent a prognostic marker and a target for new therapeutic trials. Immunohistochemistry was used to detect OPN expression, evaluated as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumours with low (<20%) from tumours with high (> or =20%) OPN expression. A statistically significant correlation between high levels of OPN and shorter overall (P = 0.034) and disease-free (P = 0.011) survival in our patients was shown. Our results support the hypothesis that high OPN expression is a significantly unfavourable prognostic factor for the survival of patients with stage I NSCLC. This conclusion has notable importance in terms of the biological characterization of early-stage tumours and therapeutic opportunities.     

Ki-67表达水平检测在乳腺癌新辅助化疗疗效评估中的价值

目的:回顾性分析88例乳腺癌新辅助化疗前、后Ki-67在肿瘤组织的表达情况,探讨Ki-67表达与新辅助化疗疗效的关系,评价其在乳腺癌新辅助化疗中的预测作用.方法:选取2015年9月至2016年9月河北医科大学第四医院乳腺中心收治的88例Ⅱ-Ⅲ期乳腺癌患者,检测新辅助化疗前空芯针穿刺肿瘤组织及术后标本中Ki-67的表达,分析其与新辅助化疗疗效及临床相关病理因素的关系.结果:新辅助化疗的临床总有效率为59.09%(52/88),Ki-67高表达组对化疗敏感,化疗效果明显优于Ki-67低表达组(P<0.05);新辅助化疗可明显降低Ki-67的高表达率(P<0.01);新辅助化疗后Ki-67表达下降组化疗有效率显著高于其他组(P<0.05).结论:Ki-67在乳腺肿瘤组织中的表达可作为新辅助化疗疗效临床评价指标之一,预测新辅助化疗的疗效,为个体化治疗提供依据.     

Inhibition of non-small-cell lung cancer cell proliferation by Pbx1

Lung cancer is one of the most deadly human cancers and continues to be a major unsolved health problem worldwide. Here, we evaluate the function of Pbx1 in the proliferation of non-smallcell lung cancer（NSCLC）. In contrast with its known proliferative function, we found that Pbx1 inhibits the proliferation of lung cancer cells. In particular, Pbx1-specific RNA interference resulted in increased proliferation in lung cancer cells. In addition, histone H3 phosphorylation was also increased following inhibition of Pbx1 expression. In contrast, Pbx1 overexpression repressed the proliferation of lung cancer cells and inhibited DNA synthesis. Collectively, our data indicate that Pbx1 inhibits proliferation in lung cancer cells, suggesting a complex role for Pbx1 in modulating the proliferation of cancer cells and making this protein a potential new target for lung cancer therapy.     

The tumour-stromal interaction between intratumoral c-Met and stromal hepatocyte growth factor associated with tumour growth and prognosis in non-small-cell lung cancer patients

Immunohistochemical analyses of the effects of hepatocyte growth factor (HGF) and c-Met expression on tumour growth and angiogenesis were performed on 88 patients with non-small-cell lung cancers (NSCLCs). In all, 22 carcinomas (25.0%) were intratumoral HGF-positive, 14 carcinomas (15.9%) were stromal HGF-positive, and 36 carcinomas (40.9%) were intratumoral c-Met-positive. None of the carcinomas were stromal c-Met-positive. Examination of tumour growth revealed that the frequency of tumours with a high Ki-67 index was significantly greater for stromal HGF-positive tumours than for stromal HGF-negative tumours (P=0.0197). The frequency of tumours with a high Ki-67 index was also significantly greater for intratumoral c-Met-positive tumours than for intratumoral c-Met-negative tumours (P=0.0301). However, there was no significant difference in tumour vascularity with relation to intratumoral HGF status, stromal HGF status, and intratumoral c-Met status. The survival rate of patients with intratumoral c-Met-positive tumours was significantly lower than for patients with c-Met-negative tumours (P=0.0095). Furthermore, the survival rate of patients with both intratumoral c-Met-positive and stromal HGF-positive tumours was significantly lower than for patients with either positive tumours, and that of patients with both negative tumours (P=0.0183 and P=0.0011, respectively). A univariate analysis revealed that intratumoral c-Met expression was a significant prognostic factor of NSCLC patients (relative risk=2.642, P=0.0029). The present study demonstrates that tumour-stromal interaction between tumour cell-derived c-Met and stromal cell-derived HGF affects tumour growth and the prognosis of NSCLC patients.     

Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role

Background:

Uncontrolled proliferation is a hallmark of malignant tumour growth. Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated in numerous studies with controversial results. We aimed to resolve these controversies by assessing the Ki-67 proliferation index (PI) in three large, independent NSCLC cohorts.

Methods:

Proliferation index was retrospectively analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with clinicopathological data including outcome and therapy. Results were validated in two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184 adenocarcinomas (ADC).

Results:

Proliferation index (overall mean: 40.7%) differed significantly according to histologic subtypes with SQCC showing a mean PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease-specific and disease-free survival were evident, in ADC high PI (optimised validated cut-off: 25%) was a stage-independent negative prognosticator (hazard ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%) was associated with better survival (HR OS: 0.65, P=0.007).

Conclusions:

Our data demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity-dependent cut-off values that allow reliable estimation of prognosis and may potentially stratify ADC patients for the need of adjuvant therapy.     

MMP-2、VEGF、CD105和Ki-67在小细胞肺癌中的表达及预后相关性研究

目的 探讨基质金属蛋白酶-2（MMP-2）、血管内皮生长因子（VEGF）、CD105和Ki 67在小细胞肺癌（SCLC）中的表达及其与临床病理特征和预后的关系。方法 收集42例SCLC和8例正常肺组织标本,采用免疫组化SP法检测MMP-2、VEGF、CD105和Ki 67在SCLC和正常肺组织中的表达,并分析其与SCLC临床病理特征和预后的关系。结果 42例SCLC组织中MMP-2、VEGF、CD105和Ki-67的阳性表达率分别为50.0％、66.7％、81.0％和64.3％,在8例正常肺组织中分别为12.5％、12.5％、0和0,差异均有统计学意义（P＜0.05）。MMP-2、VEGF、CD105的表达均与肿瘤直径、淋巴结转移、远处转移和临床分期有关,Ki-67表达与淋巴结转移有关（P＜0.05）。MMP-2、VEGF表达均与CD105和Ki-67有相关性（P＜0.05）,且MMP-2和VEGF表达呈正相关（r=0.447,P＜0.05）。单因素分析显示,肿瘤直径、淋巴结转移、远处转移、临床分期、MMP-2、VEGF、CD105和Ki 67均与总生存有关。结论 MMP-2、VEGF、CD105和Ki-67均为SCLC预后不良指标,MMP-2和VEGF可以协同促进肿瘤的新生血管形成和细胞增殖。     

TS在非小细胞肺癌组织中表达的临床病理特征

目的 最近的临床试验表明,胸苷酸合酶(TS)表达水平与非小细胞肺癌(NSCLC)使用培美曲塞化疗者预后相关.本文研究的是NSCLC癌组织中的TS表达水平与临床病理特征的关系.方法利用免疫组化法检测111例NSCLC患者的肿瘤标本的TS表达情况,并检查其与临床病理特征的联系.结果NSCLC肿瘤组织中TS表达水平与患者组织...     

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours.     

The clinical significance of Cyclin B1 and Wee1 expression in non-small-cell lung cancer.

BACKGROUND: Cyclin B1 has an important role in the G2-M phase transition of the cell cycle. Wee1 delays mitosis by suppressing the activity of the Cyclin B1/cdc2 complex. The objective of the present study was to elucidate the clinicopathological and prognostic significance of Cyclin B1 and Wee1 expression in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: An immunohistochemical assessment of Cyclin B1 and Wee1 expression was performed in 79 patients with NSCLC. RESULTS: The expression of Cyclin B1 was correlated with differentiation (P = 0.0423) and vascular invasion (P = 0.001). Patients with overexpression of Cyclin B1 had higher mean values for both the Ki-67 proliferative index (Ki-Index) (P <0.0001) and proliferating cell nuclear antigen labeling index (PCNA-LI) (P <0.0001), and a poorer prognosis (P = 0.0068). Patients lacking expression of Wee1 had a higher recurrence rate (P = 0.0084) and a poorer prognosis (P = 0.0457), and tended to have higher Ki-Index and PCNA-LI values. Multivariate analysis suggested that both Cyclin B1 (P = 0.0244) and Wee1 (P = 0.0444) expression were significant prognostic factors. CONCLUSIONS: These findings suggest that Cyclin B1 expression could be a significant prognostic parameter in NSCLC. The loss of Wee1 expression may have a potential role in promoting tumor progression and may be a significant prognostic indicator in NSCLC.     

EpCAM和Ki-67在三阴性乳腺癌原发灶及淋巴结转移灶中的表达及临床意义

目的 探讨上皮细胞黏附分子（EpCAM）和Ki-67在三阴性乳腺癌（TNBC）原发灶和淋巴结转移灶中的表达及临床意义。方法 用免疫组化染色检测81例TNBC原发灶、43例淋巴结转移灶及20例癌旁正常乳腺组织中EpCAM和Ki-67的表达情况。结果 EpCAM和Ki-67在TNBC组织中的过表达率分别为74.1％和61.7％,均高于癌旁正常乳腺组织,差异有统计学意义（P＜0.05）; EpCAM蛋白表达与TNBC的组织学分级、淋巴结转移有关（P＜0.05）;Ki-67蛋白表达与组织学分级、淋巴结转移及pTNM分期有关（P＜0.05）;TNBC组织中EpCAM和Ki-67蛋白表达呈正相关（r=0.462,P＜0.001）。在43例伴有淋巴结转移的TNBC患者中,淋巴结转移灶和原发灶中EpCAM和Ki-67蛋白均呈高表达,Ki-67在淋巴结转移灶中的表达率高于原发灶（P＜0.05）。结论 EpCAM和Ki-67在TNBC原发灶及淋巴结转移灶中均高表达;EpCAM和Ki-67过表达可能与TNBC的发生、发展密切相关。     

乳腺癌组织中Twist及Ki-67的表达及其与乳腺癌临床病理特征的相关性

目的:探讨Twist和Ki-67在乳腺癌组织中的表达,分析两者与乳腺癌临床病理特征的相关性。方法:选取62例乳腺癌组织,20例正常组织作为对照,采用免疫组化染色法分别检测 Twist和Ki-67 的表达,并检测Twist及Ki-67在不同类型及不同分子亚型乳腺癌组织中的表达。结果:在乳腺癌组织中,Twist阳性率为37.10%,Ki-67阳性率为45.16%,均高于正常组织,差异有统计学意义（P<0.01）。乳腺癌组织中 Twist和Ki-67 在肿瘤直径、ER、PR状态及组织分级分组中表达有显著性差异（P<0.05）。结论:Twist和Ki-67在乳腺癌组织中表达一致,且均呈高表达。提示两者可能与乳腺癌恶性程度分级及侵袭力有关。     

宫颈癌组织中ADAM-19、Ki-67的表达及临床意义

目的研究早期宫颈癌组织中去整合素基质金属蛋白酶-19（a disintegrin and metallopro-teinase,ADAM-19）、癌细胞增殖指数（Ki-67）的表达及临床意义。方法应用免疫组化sP法检测18例正常宫颈上皮（normal cervical epithelium,NCE）、22例宫颈上皮内瘤变（cervical intraepithelialneoplasm,CIN）和82例宫颈早期浸润癌（invasive cervix carsinoma,ICC）组织中ADAM-19和Ki-67的表达情况。结果在宫颈癌中ADAM-19表达于癌细胞浆和或细胞膜;Ki-67表达于细胞核。从正常宫颈上皮（normal cervical epithelium,NCE）到宫颈上皮内瘤变（cervical intraepithelial neoplasm,CIN）再到宫颈浸润癌（invasivecarsinomacervix,ICC）,ADAM-19、Ki-67的阳性表达率逐步升高（P〈0．05）。ADAM-19在宫颈浸润癌中的表达与盆腔淋巴结转移、脉管浸润、间质浸润、国际妇产科联盟（FIGO）分期、组织学分级和Ki-67表达有关（P〈0．05）;但与年龄和组织学类型无明显相关性（P〉0．05）。有盆腔淋巴结转移、脉管浸润、突破深层间质浸润、FIGO分期为Ⅱ期、组织学分级为Ⅲ级及Ki-67高度表达者,其ADAM-19阳性表达率显著高于无盆腔淋巴结转移、无脉管浸润、浸润深度在浅层间质以内、FIGO分期为Ⅰ期、组织学分级未超过Ⅱ级及Ki-67表达在中度以内者（P〈0．05）。结论ADAM-19阳性表达可能在癌细胞增殖和侵袭转移中起重要作用。ADAM-19过度表达者,癌细胞增殖活跃,更易发生侵袭转移,但并非唯一决定因素。检测宫颈癌中ADAM-19表达对进一步了解宫颈癌生物学行为和判断其预后有一定价值。     

VEGF、Ki-67和P53在非小细胞肺癌组织中的表达及意义

目的 检测VEGF、Ki-67和P53在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法 采用免疫组化方法检测78例NSCLC组织中VEGF、Ki-67和P53的表达情况,并结合肺癌的临床病理特征进行分析。结果 VEGF在NSCLC中的阳性表达率为67%(52/78),Ki-67在NSCLC中的阳性表达率为71%(55/78),P53在NSCLC中的阳性表达率为50%(39/78),它们的表达情况均与肿瘤组织的分化程度及临床分期有关(P＜0.05),与肺癌的组织学分型、有无淋巴结转移及年龄无关(P＞0.05),肿瘤组织分化越差、临床分期越晚者三者表达的阳性率越高。VEGF、Ki-67和P53表达阳性者总生存时间明显差于阴性表达者(P＜0.05)。结论 VEGF、Ki-67和P53与肺癌的发生、发展有关,对于判断非小细胞肺癌的预后及指导治疗有重要的参考意义。     

Ｋ-ｒａｓ蛋白在非小细胞肺癌中的表达及其临床意义

目的　探讨Ｋ-ｒａｓ蛋白在非小细胞肺癌（ＮＳＣＬＣ）组织和癌旁组织中的表达情况及其与ＮＳＣＬＣ临床病理参数的相关性。方法　通过免疫组化方法检测大连市不同医院诊断明确的ＮＳＣＬＣ手术切除标本９５例,其中２９例标本取癌旁组织,检测各标本中Ｋ-ｒａｓ蛋白的表达。结果　Ｋ-ｒａｓ蛋白在ＮＳＣＬＣ组织中的表达率为４５２６％,在癌旁组织为２４.１４％（Ｐ＜０.０１）。ＮＳＣＬＣ组织中Ｋ-ｒａｓ蛋白表达与组织学类型显著相关,腺癌表达率为５６.２５％,明显高于鳞癌的２２.５８％（Ｐ＝０.００４２）;与性别、年龄、分化程度、ＴＮＭ分期、淋巴结转移等无关。结论　ＮＳＣＬＣ中存在Ｋ-ｒａｓ蛋白表达上调。其高表达更易发生于肺腺癌。