Expression of the Forkhead transcription factor FOXP1 is associated with tumor grade and Ki67 expression in clear cell renal cell carcinoma

Expression of FOXP1 and Ki67 was immunohistochemically assessed on tissue microarrays of 129 cases of clear cell renal cell carcinomas. Overall and disease-specific survival correlated inversely with pT-category, grading and lymph node metastasis in (p < .05). Expression of FOXP1 correlated negatively with tumor grading (p = .02), but neither with pT-category nor with lymph node metastasis. Significant positive correlation was shown for Ki67 expression and tumor stage and lymph node metastasis (p < .05). The overall survival and the disease-specific survival correlated negatively with the Ki67 status (p < .05). FOXP1 expression negatively correlated with Ki67 expression in clear cell renal cell carcinomas (p = .036).     

c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival.

The prognostic significance of c-erbB-2 oncoprotein overexpression detected in tumours by immunocytochemical assays (ICAs) was investigated in 148 breast carcinomas. ICAs were performed under optimal technical conditions with frozen tissue sections and included automated immunoperoxidase technique and computer-assisted analysis (densitometry) of digitized coloured microscopic images. Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive surfaces and mean optical densities) were correlated with the patients'' follow-up in axillary lymph node-positive (N+) and node-negative (N-) subgroups of patients. Patients'' follow-up ranged from 9 months (for the first death) to 101 months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off point 35%) significantly correlated with the patients'' poor overall survival in N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015). Also, marked c-erbB-2 immunohistochemical expression correlates with short disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups. It is concluded that in optimal conditions (automated and quantitative ICAs on frozen sections) c-erbB immunohistochemical expression is a significant prognostic indicator in terms of overall and disease-free survival. The c-erbB-2 protein prognostic significance is independent of node status in terms of overall survival, but not of disease-free survival.     

Prognostic significance of Ki67 (MIB1) proliferation index and p53 over-expression in chondrosarcomas

To investigate the prognostic significance of the Ki67 (MIB1)-proliferation index and p53 over-expression in chondrosarcomas, we retrospectively analyzed a cohort of 29 patients with chondrosarcomas using immunohistochemical assays with MIB1 and p53 monoclonal antibodies on formalin-fixed, paraffin-embedded tissue samples with microwave preparation. We also assessed 19 patients with benign cartilaginous tumors as a control group. There was a significant positive correlation between MIB1 index and tumor grade in chondrosarcomas, while there was no significant difference in the MIB1 index between the grade-I chondrosarcomas and the benign cartilaginous tumors. Patients categorized in the high-MIB1-index group had a significantly lower survival rate than those in the low-index group. Moreover, in analyzing the sub-set of the patients with grade-II chondrosarcomas, it was found that they could be prognostically sub-divided according to MIB1 index. The p53 index also significantly correlated with patient survival, and there was significant correlation between the MIB1 index and the p53 index. However, in multivariate analysis, only the MIB1 index and tumor grade proved to be independent prognostic indicators of chondrosarcomas. These results demonstrate that the MIB1 index can be a useful procedure for assessing tumor grade in chondrosarcomas, especially for determining the prognosis of patients with grade-II chondrosarcoma. © 1996 Wiley-Liss, Inc.     

Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004).The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.     

Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas.

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients'' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).     

Quantitative imaging of ps2 immunocytochemical assays in breast carcinomas

pS2 expression was studied in 212 breast carcinomas. Immunocytochemical assays (ICAs) were performed on frozen sections and evaluated by digital image analysis. pS2 immunostaining was compared in frozen sections and paraffin sections. The pS2 positivity was observed in 45% of the cases on frozen sections. But in pS2 positive tumors, the tumor surface which was immunostained was small (m=14.3%). In 22% of immunoreactive tumors the positive surface was 5% or less. In contrast to frozen sections, the pS2 positivity on paraffin sections could not be evaluated by image analysis system because of the background. No significant correlation was observed between pS2 expression and patient age, tumor size, histological type and grade, nor with lymph node status. The pS2 positivity was significantly correlated to ER and PR positive immunodetection on frozen sections. But pS2 was independent from pHER-2/neu and cathepsin expression whereas there was a significant inverse relationship between pS2 and Ki67. This study shows that pS2-ICAs on frozen sections and image analysis are optimal and standardized conditions for the evaluation of pS2 expression in breast carcinomas, and suitable for selecting patients for hormone therapy.     

Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival

Background: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. Materials and Methods: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. Results: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. Conclusions: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.     

The combined evaluation of p53 accumulation and of Ki-67 (MIB1) labelling index provides independent information on overall survival of ovarian carcinoma patients

Background: The prognostic implications of p53 accumulation, bcl-2immunoreactivity and tumour proliferative fraction in ovarian carcinomas arestill debated.Patients and methods: One hundred twelve ovarian carcinomas wereimmunostained for p53 protein, for bcl-2 and for the cell cycle-associatedKi-67 antigen. The immunostaining results were correlated with conventionalclinico-pathological variables, response to induction chemotherapy, andpatient survival.Results: p53 accumulation and bcl-2 immunoreactivity in more than10% of neoplastic cells were detected in 61 (54.5%) and 42(37.5%) cases, respectively. A positive correlation between p53accumulation and high (more than 30% neoplastic cells) MIB1 labellingindex (r = 0.235; P = 0.015) was ascertained, whereas no significantassociation was found between bcl-2 immunoreactivity and p53 accumulation orMIB1 labelling index. Both p53 accumulation and MIB1 immunoreactivitycorrelated significantly with a reduced overall survival, but the associationwas lost in multivariate analysis. However, patients with tumourssimultaneously showing p53 accumulation and MIB1 labelling index higher than30% had significantly reduced overall survivals, in both univariate andmultivariate analyses.Conclusion: The simultaneous evaluation of p53 accumulation and MIB1labelling index has independent prognostic implications in common epithelialmalignancies of the ovary, irrespective of the disease stage.     

High prognostic impact of growth fraction parameters in advanced stage laryngeal squamous cell carcinoma

One hundred and two cases of laryngeal squamous cell carcinoma, all treated in the same center with total or supraglottic laryngectomy, bilateral neck dissection and postoperative radiotherapy, were investigated with both Ki67 and MIB-1 monoclonal antibodies. The aim was to determine the prognostic impact of growth fraction markers in a homogeneous series of patients. All samples were stained with Ki67 monoclonal antibody on frozen sections, and with MIB-1 monoclonal antibody on paraffin sections, using the ABC immunoperoxidase method. The percentage of positive cells was compared in each case with the overall and disease-free survival, pathologic stage and histologic grading. The values obtained from Ki67 and MIB-1 counts were similar and highly correlated (r=0.90). Two groups of cases with low and high proliferation rate (59 and 43 respectively) were obtained by splitting up the whole series, on the basis of the median value; 84. 6% of the patients with high proliferation relapsed and/or died due to the tumor within two years from diagnosis whereas, at time of writing, 94% of the patients with low proliferation are alive and well (p<0.00001). No relation was found between growth fraction and histologic grading, pathologic stage (pT and pN) and site of the tumor. Only lymph node involvement was correlated with disease-free survival. Our results indicate that Ki67/MIB-1 index represents an independent variable to determine long-term prognosis in laryngeal squamous cell carcinomas. We recommend its use in diagnostic protocols, to distinguish high risk subsets of patients who might benefit from more aggressive treatments.     

Prognostic significance of angiogenesis evaluated by CD105 expression compared to CD31 in 905 breast carcinomas: correlation with long-term patient outcome

Our purpose was to determine the respective prognostic significance of CD105 and CD31 immunoexpression in node negative patients with breast carcinoma, since angiogenesis induces blood borne metastases and death in carcinomas. CD105 (endoglin) has been reported as expressed by activated endothelial cells and consequently should better reflect neoangiogenesis in malignant tumors. Comparison of CD31 and CD105 immunocytochemical expression was undertaken in a series of 905 breast carcinomas. Results were compared to patients' long-term (median = 11.3 years) outcome. Univariate (Kaplan-Meier) analysis showed that the number of CD105+ microvessels (cut-off 15 vessels) correlated significantly with poor overall survival (p=0.001). This correlation was less significant in node negative patients (p=0.035). The number of CD31+ microvessels (cut-off 25 vessels) similarly correlated with poor survival (p=0.032) but not in the subgroup of node negative patients. Marked CD105 expression also correlated with a high risk for metastasis in all patients (p=0.0002) and in the subset of node negative patients (p=0.001). Similarly metastasis risk in node negative patients correlated with marked CD31 immunocytochemical expression (p=0.02). Multivariate analysis (Cox model) identified CD105, but not CD31 immunoexpression, as an independent prognostic indicator. Our results suggest that: i) in breast carcinomas, immunoselection of microvessels containing activated CD105 labelled endothelial cells is endowed with a stronger prognostic significance, as compared to CD31 vessels labelling; ii) the CD105 immunoexpression may be considered as a potential tool for selecting node negative patients with a poorer outcome and higher metastasis risk; iii) in these patients specific antiangiogenic therapy targeted by anti-CD105 conjugates can be further developed.     

Ki - 67、AR 及 FRA 在三阴性乳腺癌中的表达及意义

目的：观察Ki-67、雄激素受体（androgenreceptor,AR）和a-叶酸受体（folatereceptoralpha,FRA）在三阴性乳腺癌（triplenegativebreastcancer,TNBC）组织中的表达,探讨Ki-67、AR、FRA与TNBC预后的关系。方法：应用免疫组织化学法检测Ki-67、AR及FRA在80例TNBC组织中的表达,分析其与TNBC患者临床病理特征的相关性及与预后的关系。结果：TNBC组织中Kj-67、AR、FRA阳性率分别为81．25％、25．00％、71．25％。Ki-67、FRA阳性表达率与TNBC患者高淋巴结转移、低组织学分级和5年生存时间有关,并有统计学意义（P〈0．05）。AR阳性表达率与TNBC高组织学分级和5年生存时间有关且有统计学意义（P〈0．05）。Ki-67、FRA表达高者,生存时间短,且与5年生存时间呈负相关（r=-0．371,r=-0．498）;AR表达高者,生存时间长,与5年生存时间呈正相关（r=0．465）。Ki-67与FRA表达呈正相关（r=0．332）,与AR表达呈负相关（r=-0．462）。结论：TNBC组织中Ki-67、FRA阳性者预后差,AR阳性者预后良好,联合检测这三个抗体的表达,可能为评价TNBC预后提供新指标,为TNBC的治疗提供新靶点。     

非小细胞肺癌PET-CT标准摄取值与葡萄糖转运蛋白1和微血管密度及Ki67表达的相关性

目的 分析非小细胞肺癌(NSCLC)18F-氟代脱氧葡萄糖(18F-FDG)标准摄取值(SUV)与葡萄糖转运蛋白l(GLUTl)、微血管密度(MVD)及Ki67表达的相关性.方法 收集经18F-FDGPET-CT检查并手术切除的NSCLC 33例,采用免疫组织化学DP法,分别检测GLUTl、MVD和Ki67,并将三者与18F-FIX;的SUV进行对比.结果 33例NSCLC患者中,Ⅰ期21例,Ⅱ期4例,Ⅲa期8例.33例NSCLC标本中,GLUTl阳性者22例(12例腺癌,10例鳞癌),阴性者11例(10例腺癌,1例鳞癌),阳性率为66.7%;Ki67阳性者24例(13例腺癌,11例鳞癌),阴性者9例(均为腺癌),阳性率为72.7%;CD34阳性者33例,阳性率为100.0%,标本平均MVD为(12.6±2.9)条,33例NSCLC的SUV为1.4～27.4,中位数为10.1.结论 18F-FDlG PET的SUV与GLUTl呈线性相关,SUV与Ki67表达和MVD无相关性.GLUTl、Ki67和CD34与病灶大小及有无淋巴结转移无相关性.     

表皮生长因子受体EGFR和Ki67在非小细胞肺癌中的表达及其相关性研究

目的 :探讨表皮生长因子受体 (epi dermalgrowthfactorreceptor ,EGFR)和Ki67在非小细胞肺癌 (non smallcelllungcancer,NSCLC)中的表达及其与NSCLC发生、发展及预后的关系。方法 :对经随访资料完整的术后NSCLC组织标本 60例、癌旁组织 2 0例和肺正常组织 5例 ,采用SP免疫组化法检测EGFR和Ki67。对术后辅助性化疗 3 6例 ,分析疗效与EGFR和Ki67表达的关系。结果 :NSCLC中EGFR表达阳性率为 65 % ,阳性细胞的棕黄色颗粒位于细胞质 ;Ki67表达阳性率为 81 67% ,阳性细胞的棕黄色颗粒位于细胞核 ;2 0例癌旁组织及 5例正常肺组织未见阳性染色细胞。癌组织EGFR和Ki67表达与癌旁组织相比差异有统计学意义 ,P <0 0 1。NSCLC中EGFR和Ki67阳性表达与年龄、性别、吸烟与否、肿瘤细胞的病理类型差异无统计学意义 ,P >0 0 5 ;与肿瘤大小、病理分级、淋巴结转移和TNM分期密切相关 ,P <0 0 5。EGFR和Ki67表达阳性者 3年生存率分别为19 86%和 3 1 3 3 % ,低于阴性表达 70 11%和90 91% ,P <0 0 5 ;接受术后辅助性化疗的患者 ,EGFR和Ki67阳性表达复发转移率分别为 70 3 7%和 62 5 0 % ,高于阴性表达 11 11%和 0 ,P <0 0 5。结论 :EGFR和Ki67在NSCLC中的异常或过度表达与肿瘤发生、发展密切相关 ,两者表达具有协同作     

MIB1/Ki-67 labelling index can classify grade 2 breast cancer into two clinically distinct subgroups

Histological grade is recognized as one of the strongest prognostic factors in operable breast cancer (BC). Although grade 1 and grade 3 tumours are biologically and clinically distinct, grade 2 tumours bear considerable difficulty in outcome prediction and planning therapies. Several attempts such as genomic grade index have been performed to subclassify grade 2 into two subgroups with clinical relevance. Here, we present evidence that the routinely evaluable immunohistochemical MIB1/Ki67 labelling index (MIB-LI) can classify grade 2 tumours into two clinically distinct subgroups. In this study, growth fractions of 1,550 primary operable invasive breast carcinomas were immunohistochemically assayed on full-face tissue sections using the MIB1 clone of Ki-67. Growth fractions were assessed as number of MIB1 positive nuclei in 1,000 tumour nuclei at high-power magnification and expressed as MIB1-LI. Using a 10% cut-point of MIB1-LI, grade 2 BCs were classified into low (49.8%) and high (50.2%) proliferative subgroups. Univariate and multivariate survival analysis revealed statistically significant differences between these subgroups regarding patients’ BC specific survival (P < 0.001), and metastasis free survival (P < 0.001) which was independent of the well-established prognostic factors (HR = 2.944, 95% CI = 1.634–5.303, P < 0.001). In conclusion, our results further demonstrate that grade 2 BCs may represent at least two biological or behaviourally different entities. Assay of growth fraction in BC using MIB1/Ki67 immunohistochemistry is a robust cost-effective diagnostic tool that subdivides grade 2 tumours into low and high risk populations providing additional prognostic information in planning therapies and outcome prediction.     

VLA(3)/integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry

VLA, expression was immunohistochemically investigated in 145 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA, using automated (Ventana ES 320 system) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA, immunoreaction was observed in 86 tumors (23.5%) within epithelial cells of carcinomas. The positive surface in tumors varied from 3% to 38% (mean = 13.8%, SD=11.5) and was independent of the tumor size, grade, type and aneuploidy, and of nodal status. VLA(2) was significantly correlated with VCAM (p<0.01), VLA(2) (p<0.01), E cadherin (p=0.025), and CD44 v (p<0.01), and an inverse relationship was observed with Ki67/MIB 1 (p=0.0024) and P-53 (p=0.034). In contrast VLA, expression proved to be independent of Bcl-2, c-erbB-2, cathepsin D, tenascin, CD31, ELAM, RE, RP, PS2 immunohistochemical expression. The results suggest that VLA, expression in tumors is related to the regulation of other adhesion molecules involved in the metastasis process, but the prognostic significance and clinical relevance of VLA, immunodetection in breast carcinomas remain to be demonstrated.     

脑膜瘤Ki—67MIB—1的表达及其诊断价值

目的　研究肿瘤细胞增殖活性及其在诊断脑膜瘤中的价值。　方法　应用Ｋｉ６７ ＭＩＢ１ 免疫组织化学方法,检测其在脑膜瘤中的表达。　结果　良性脑膜瘤的Ｋｉ６７ ＭＩＢ１ 平均指数为２４５％ ,非典型脑膜瘤为５５ ％ ,恶性脑膜瘤为１１２ ％ 。良性脑膜瘤与非典型脑膜瘤比较差异有显著性（ Ｐ＜ ０００１）,非典型脑膜瘤与恶性脑瘤比较差异有显著性（ Ｐ＜ ０００１） 。核分裂与Ｋｉ６７ ＭＩＢ１ 表达呈相关性（ｒ＝ ０７７９ ,Ｐ＜０００１）。　结论　Ｋｉ６７ＭＩＢ１ 染色有助于脑膜瘤的正确诊断。     

Clinicopathological significance of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinoma

To investigate the expression of TSPAN1 (Gene ID: 10103), Ki67 and CD34 in gastric carcinomas and the clinicopathological significance, the expression of TSPAN1, Ki67 and CD34 was detected in 86 cases of gastric carcinoma, paraffin-embedded sections using an immunohistochemical method. The rates of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinomas were 56.98%, 74.42%, and 62.79%, respectively. The overexpression of these markers was positively correlated with clinical stage and negatively correlated with survival rates (at 3 and 5 years). The overexpression of TSPAN1 and Ki67 was negatively correlated with carcinoma differentiation, and the overexpression of TSPAN1 and CD34 was positively correlated with infiltration and lymph node status of the tumor. Thus, overexpression of TSPAN1, Ki67 and CD34 in gastric cancer tissues is associated with development of the cancer. The detection of expression of TSPAN1, Ki67 and CD34 in gastric cancer may provide useful prognostic information for patients with the disease.     

Expression of her-2/neu oncogene in breast-cancer - correlation of quantitative immunocytochemistry and prognostic factors

HER-2/neu oncogene expression by breast carcinomas (n = 208) was investigated on frozen sections using monoclonal anti-p185 HER-2/neu protein. Results were evaluated by computer-assisted image analysis and correlated with morphological prognostic factors, hormone receptor antigenic sites, Ki 67 antigen and cathepsin content, nuclear morphometry, DNA content and Ag NORs, which were also evaluated by image analysis. All tumors were anti-p185 HER-2/neu immunoreactive, but in 40% of the cases, less than 20% of the tumor cell surface was immunostained. In terms of both extent and intensity, immunostaining which was greatest in comedocarcinomas correlated with tumor size (p = 0.019) and Ki 67 (p = 0.0012) and cathepsin (p<0.0001) content. No correllation was found with tumor grade, axillary lymph node involvement, hormone receptor sites, nuclear DNA content and Ag NORs distribution and morphometry.     

PCNA和Ki67抗原与喉癌的相关性研究

目的 :探讨增殖细胞核抗原 (PCNA)和Ki6 7抗原表达与喉癌临床病理及预后的关系。方法 :采用流式细胞免疫法检测 4 0例喉鳞状细胞癌患者 (声门上型 13例 ,声门型 2 7例 )PCNA和Ki6 7抗原表达 ,同时检测 12例癌旁正常组织作为对照组。结果 :癌组织与癌旁组织间PCNA和Ki6 7表达差异有极显著意义 ,P <0 0 0 1;高、中分化鳞癌与低分化鳞癌间差异有极显著意义 ,P <0 0 1;淋巴结转移阳性组与阴性组间差异有显著意义 ,P <0 0 5 ;无复发生存组与复发、死亡组间差异有显著意义 ,P <0 0 5 ;早期组 (Ⅰ、Ⅱ )与晚期组 (Ⅲ、Ⅳ )间差异无显著意义 ,P >0 0 5。结论 :PCNA和Ki6 7抗原表达与喉癌的病理分级和淋巴结转移呈显著正相关 ,与临床分期无关 ,两参数高表达是喉癌重要生物学特征。     

Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma

The degree of angiogenesis in breast cancer has previously been shown to be an indicator of prognosis, and tumor microvasculature is a candidate target for new antiangiogenic therapies. The aim of this study was to investigate the prognostic value of vascular endothelial growth factor (VEGF) receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1), and Tie2/tek receptor tyrosine kinase in breast carcinoma. VEGF receptors and Tie2 expression was investigated using immunohistochemical assays with monoclonal antibodies on frozen sections in a series of 918 and 909 patients respectively. VEGFR-1 and VEGFR-2 and Tie2 were correlated with long-term (median, 11.3 years) patients' outcome. Univariate (Kaplan-Meier) analysis showed that VEGFR-1 positive tumor surface (cutoff = 5%) was significantly correlated with high metastasis risk (p=0.03) and relapse (p<0.01) in all patients, and in those with node negative tumors (p<0.001 and p<0.01 respectively), but not with overall survival. In contrast Tie2 positive tumor surface (cutoff = 7%) was significantly correlated with poor overall survival (p=0.025) and also with high metastasis risk particularly among node negative patients (p<0.01). Moreover, Tie2 immunoexpression was significantly predictive of relapse (p=0.003) in the node negative subgroup (p=0.02). In multivariate analysis (Cox model), VEGFR-1 and Tie2 immunoexpressions were identified as independent prognostic indicators. In contrast, univariate analysis showed that VEGFR-2 positive tumor surface (cutoff = 10%) was not correlated with survival or with metastasis and relapse risk. Our results suggest that VEGFR-1 and Tie2 immunohistochemical expression permits the identification of patients with poor outcome, and particularly node negative ones with a high risk for metastasis and relapse. VEGFR-1 and Tie2 immunodetection may also be considered as potential tools for selecting patients who could benefit in the future from specific antiangiogenic therapy interfering with VEGFR-1 and Tie2 activation pathways.