人脑胶质瘤血管生成与基质细胞衍生因子-1α表达的相关性

目的:探讨基质细胞衍生因子-1α(stromal cell derived factor-1α,SDF-1α)在人脑胶质瘤中的表达及其与胶质瘤血管生成的相关性.方法:以58例人脑胶质瘤及18例正常脑组织为研究对象,应用免疫组织化学方法检测SDF-1α及CD105的表达情况,并计数CD105标记的微血管密度(microv...     

乳腺癌组织Livin和PTEN表达与肿瘤血管生成的相关性

目的:研究乳腺癌组织中凋亡抑制蛋白Livin和抑癌基因PTEN的表达与微血管密度(MVD)的关系,探讨乳腺癌血管生成的影响机制。方法:应用免疫组化Elivision法检测90例乳腺癌和30例乳腺纤维腺瘤组织中Livin、PTEN、VEGF的表达和CD34标记的MVD值,分析Livin和PTEN表达与乳腺癌血管生成及侵袭转移的关系。结果:在90例乳腺癌中Livin、PTEN和VEGF表达阳性率分别为54.4%、48.9%和61.1%,MVD为(30.81±11.29)个/HPF,与良性对照组比较均有显著差异(P<0.01);Livin阳性表达与乳腺癌肿瘤大小、临床分期、MVD值及VEGF表达呈正相关(P<0.05),与年龄、病理分级、淋巴结转移未见显著相关(P>0.05);PTEN表达与乳腺癌淋巴结转移、临床分期和MVD呈负相关(P<0.05),与VEGF表达、年龄、肿瘤大小、病理分级未见显著相关(P>0.05)。结论:Livin和PTEN在乳腺癌的血管生成及发生发展过程中分别起促进和抑制作用,Livin的促血管生成作用可能与其上调VEGF的表达有关。     

CD105- and CD31-assessed microvessel density in laryngeal carcinoma biopsies as a predictor of recurrence after exclusive primary surgery

PurposeSurgery is currently indicated as a unimodal therapeutic approach with curative intent in selected laryngeal squamous cell carcinomas (LSCCs) ranging from stage I to III. The main aim of this study was to evaluate the prognostic role of CD105- and CD31-assessed microvessel density (MVD) in biopsy and in surgical specimens from a cohort of consecutive stage I-III LSCCs who had undergone exclusive primary surgery, according to current guidelines.Materials and methodsCD105- and CD31-assessed MVD were analyzed in paired biopsies and surgical specimens of 24 consecutive cases of LSCC who underwent exclusive surgery.ResultsOn biopsy specimens, CD105- and CD31-assessed MVD were positively associated with recurrence risk (hazard ratio [HR] 1.266, p = 0.0034 and HR 1.265, p = 0.0081, respectively). In surgical specimens, CD105- and CD31-assessed MVD were significantly associated with disease-free survival (DFS) (HR 1.213, p = 0.0016 and HR 1.237, p = 0.0023 respectively). Considering a stratification based on median value, recurrence risk was higher in patients with a CD105-assessed MVD>0 in both biopsies and surgical specimens (HR 11.005, p = 0.0326 and HR 34.483, p = 0.0311). No significant differences in terms of recurrence risk were found for CD31-assessed on biopsies or on surgical specimens.ConclusionsThis study supports the role of biopsy CD105-MVD as a predictor of recurrence after exclusive surgery for LSCCs. Further prospective studies are mandatory to better characterize the prognostic role of CD105-MVD evaluated on biopsies to develop novel criteria to identify patients at higher risk of recurrence for more aggressive approaches or adjuvant treatment.     

Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer

AIMS: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB-IIA non-small cell lung cancer (NSCLC). METHODS: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105. RESULTS: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p = 0.04). Univariate analysis showed that those patients with VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression (p = 0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p = 0.0002). CONCLUSIONS: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC. This may be because these factors are more closely related to the metastatic process.     

Comparative evaluation of microvessel density determined by CD34 or CD105 in benign and malignant gastric lesions

Microvessel density (MVD) is regarded as a surrogate marker for angiogenesis and has been used for tumor prognosis. In this study, MVD was identified immunohistochemically by monoclonal antibodies against CD105 and CD34 in the tissues representing gastric carcinoma, chronic gastritis, and hyperplastic polyps, and the results were correlated with clinicopathologic features. The expression of CD105 in the microvessels within benign lesions was barely visible, and MVD was markedly lower than that determined by CD34. CD34 was strongly expressed in the microvessels within hyperplastic polyps and tissues with gastritis. In gastric carcinoma, CD105 expression in microvessels was as high as the MVD, compared with benign lesions. CD105 stained well-formed mature and newly formed immature vessels within the cancer mass. Correlation analysis showed that MVD determined by CD105 correlated with blood vessel invasion, distant metastasis, and formation of ascites. Survival analysis demonstrated an inverse correlation between MVD count and overall survival: patients with MVD counts of 32 or higher survived for a much shorter time than those with counts lower than 32. Multivariate analysis confirmed that MVD determined by CD105 was an independent prognostic factor for survival. Microvessel density determined by CD34 inversely correlated with overall survival, but it did not correlate with other clinicopathologic parameters except formation of ascites. In conclusion, CD34 was universally expressed in blood vessels within benign and malignant tissues, whereas CD105 expression was minimal in benign tissues but stronger in gastric carcinoma. These data suggest that both CD105 and CD34 could be used for quantification of angiogenesis, but preference should be given to CD105 in the evaluation of prognosis in gastric carcinoma.     

Endoglin (CD105) expression in angiogenesis of primary hepatocellular carcinomas: analysis using tissue microarrays and comparisons with CD34 and VEGF

Few studies about angiogenesis in hepatocellular carcinoma (HCC) have been conducted and little is known about the significance of angiogenesis in HCC. In this study, the clinicopathological significance of tumor microvessel density (MVD) was assessed in 105 patients with HCC by immunohistochemical staining of CD105, CD34, and vascular endothelial growth factor (VEGF). Moreover, the use of the tissue microarray technique in evaluating angiogenesis of HCC was appraised. The MVD by CD105 immunostaining (MVD-CD105) was significantly lower in larger tumors (5 cm diameter as a cutoff point, p=0.001), more aggressive tumors, as indicated by venous infiltration (present vs absent, p=0.001), and tumors with advanced TNM stage (stage I & II vs stage III, p=0.011). A lower score of MVD by CD34 immunostaining (MVD-CD34) showed significant association only with venous invasion (p<0.001), whereas the MVD by CD105 immunostaining in tissue microarray (MVD-MA) was significantly lower only in larger sized tumors (p=0.043). Moreover, MVD-CD105 was positively associated with the expression intensity of VEGF (p=0.009), but not for MVD-CD34 (p=0.088). When median scores of MVD were used as cut-off points, the patients with higher score of MVD-CD105 had a significantly poorer prognosis in either disease-free or overall survival analysis (p=0.002 and p=0.009, respectively), whereas similar prognostic significance of MVD-CD34 was not observed in overall survival analysis (p=0.052) but was observed in disease-free survival analysis (p=0.022). No prognostic significance of MVD-MA was found in either disease-free or overall survival analysis (p=0.277 and p=0.712, respectively). These data demonstrate the superiority of CD105 over CD34 as a marker of angiogenesis in HCC and indicate that the tissue microarray technique is unsuitable for evaluating angiogenesis in HCC.     

Prognostic Impact of Angiogenesis in Nonmuscle Invasive Bladder Cancer as Defined by Microvessel Density after Immunohistochemical Staining for CD34

Bladder cancer is the second most common malignancy of the urogenital region. The majority of bladder cancer deaths occur as a consequence of metastatic disease. Microvessel density (MVD), a surrogate marker for angiogenesis, has been shown to be predictive of progression and poor prognosis. The aim of this study was to evaluate the predictive value and prognostic significance of angiogenesis in human non muscle invasive bladder cancer (NMIBC) treated by BCG immunotherapy. The frozen sections of 28 non muscle invasive bladder cancer specimens were stained with CD34 antibody to label the vascular endothelium using the standard streptavidin-biotin immunoperoxidase method. Angiogenic activity was measured using microvessel count determined by the expression of vascular markers CD34.The prognostic significance of tumor stage, grade, loci number, tumor size, age and CD34 expression in determining the risk for recurrence was studied with both univariate and multivariate methods of analysis. According to univariate analysis of the prognostic significance for tumor stage, grade, tumor size, loci number, age and CD34 expression, in patients with NMIBC, the pT1 stage and high grade seem to be associated in a statistically significant manner with higher risk for recurrence (P=0.004, P=0.004, respectively). In the other hand, multivariate Cox regression's analysis showed that microvessel density and multiplicity were independent predictor of recurrence after BCG immunotherapy (p=0.016, p=0.032, respectively). This study provides strong evidence that CD34 MVD is associated with recurrence after BCG immunotherapy. Independent studies, however, will be required on larger cohort to validate these findings.     

Prognostic Impact of Angiogenesis in Nonmuscle Invasive Bladder Cancer as Defined by Microvessel Density after Immunohistochemical Staining for CD34

Bladder cancer is the second most common malignancy of the urogenital region. The majority of bladder cancer deaths occur as a consequence of metastatic disease. Microvessel density (MVD), a surrogate marker for angiogenesis, has been shown to be predictive of progression and poor prognosis. The aim of this study was to evaluate the predictive value and prognostic significance of angiogenesis in human non muscle invasive bladder cancer (NMIBC) treated by BCG immunotherapy. The frozen sections of 28 non muscle invasive bladder cancer specimens were stained with CD34 antibody to label the vascular endothelium using the standard streptavidin-biotin immunoperoxidase method. Angiogenic activity was measured using microvessel count determined by the expression of vascular markers CD34.The prognostic significance of tumor stage, grade, loci number, tumor size, age and CD34 expression in determining the risk for recurrence was studied with both univariate and multivariate methods of analysis. According to univariate analysis of the prognostic significance for tumor stage, grade, tumor size, loci number, age and CD34 expression, in patients with NMIBC, the pT1 stage and high grade seem to be associated in a statistically significant manner with higher risk for recurrence (P=0.004, P=0.004, respectively). In the other hand, multivariate Cox regression’s analysis showed that microvessel density and multiplicity were independent predictor of recurrence after BCG immunotherapy (p=0.016, p=0.032, respectively). This study provides strong evidence that CD34 MVD is associated with recurrence after BCG immunotherapy. Independent studies, however, will be required on larger cohort to validate these findings.     

High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma

Aims: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC. Methods: Twist expression was examined by immunohistochemical techniques in 156 formalin-fixed specimens. Cell proliferation, angiogenesis, and apoptosis were measured as the percentage of Ki-67-positive cells (proliferation index, PI), CD31-stained vessels (microvessel density, MVD), and TUNEL-positive cells (apoptotic index, AI). In addition, semi-quantification of matrix metalloproteinase (MMP)-2 was performed. Macrophages were identified with anti-CD68 antibody, and the tumor associated macrophage (TAM) density was calculated as CD68-positive cells per high-power field. Results: Twist expression was positively associated with grade, pT stage, and metastasis (p<0.001). We also noticed that its expression was considerably higher in cancer cells of sarcomatoid RCC and in those at the edge of the tumors. Twist expression was positively correlated with PI, MVD, MMP2 expression, and TAM density (P<0.001), but not with AI, and MMP-2 expression and TAM density were independently correlate by multi-variate analyses. Kaplan-Meir survival curves showed high Twist expression was a worse predictor for cause-specific survival (P<0.001). Conclusions: Twist plays important roles in tumor growth, progression, and survival in patients with RCC patients. Such pathological mechanisms are significantly associated with increased cancer cell proliferation, angiogenesis, MMP2 expression, and macrophage recruitment. These findings are important information for discussion of treatment and observation strategies in these patients.     

Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas

Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.     

High cytoplasmic HuR expression is associated with advanced pT stage,high grade and increased microvessel density in urothelial bladder carcinoma

PurposeHuR (human antigen R) protein is a RNA binding protein that stabilizes the mRNA and controls the translation of genes involved in cell proliferation, differentiation, and carcinogenesis. Overexpression of HuR was reported in a variety of cancers, however its clinical significance in urothelial bladder cancer (UBC) is still unknown. Our aim is to investigate the association between HuR expression and selected histopathological factors, such as tumor grade, pT stage, regional lymph nodes status and microvessel density (MVD).MethodsWe studied expression of HuR protein in 119 patients with UBC in stages pTis and pTa–pT4 using immunohistochemistry (IHC). Tumor MVD was evaluated immunohistochemically using anti-CD31 antibody.ResultsWe observed no association between nuclear HuR immunoreactivity and tumor grade, stage or MVD. We found a significant association between cytoplasmic HuR positivity and high tumor grade, pT stage and MVD (p < 0,001). We also observed significantly higher MVD values in cases with positive cytoplasmic HuR expression (p < 0,001). No association between HuR immunoreactivity and lymph nodes status was found.ConclusionsOur results may suggest that HuR is involved in the process of acquiring malignant histopathological features and ability to invade the muscularis propria by UBC cells. Considering frequent difficulties in diagnosing UBC in specimens obtained from transurethral tumor resection and the risk of understaging, cytoplasmic HuR expression would suggest an advanced disease and necessitate serial sectioning of the specimen in search of muscle invasion. Association between HuR expression and MVD could suggest HuR involvement in the process of angiogenesis in UBC.     

子宫内膜良、恶性增生组织的CD105(Endoglin)的表达及其意义

目的研究正常、良性及恶性增生子宫内膜组织中新生血管标志物CD105(Endoglin)的表达,与传统总内皮标志物CD34的比较,并探讨组织微血管密度(microvesseldensity,MVD)的临床病理意义.方法采用S-P免疫组织化学染色法检测43例子宫内膜腺癌、15例子内膜不典型增生过长、15例复杂型增生、15例简单型增生及20例正常子宫内膜(10例分泌期内膜和10例增生期内膜)的CD105和CD34的表达情况.结果CD105和CD34标记的组织中的微血管密度(MVD)在子宫内膜从正常子宫内膜到简单型增生、复杂型增生到不典型增生的发展过程中表达逐渐增加,各组间差异有意义(P＜0.05).CD105标记的MVD在不典型增生与内膜癌间则没有明显区别,而CD34标记的MVD在这两组间有显著性差异(P＜0.05).在子宫内膜癌中只有CD105标记的MVD与子宫内膜癌的FIGO分期、病理分级、肌层浸润深度和淋巴结转移相关,CD34标记的MVD则不相关.结论新生血管标志物CD105比通常用的总内皮标记物CD34更好,是一种更有特异性的肿瘤血管内皮标志,它标记的肿瘤内微血管计数(MVD)对评估子宫内膜恶性增生程度有重要意义.     

Reduced PTEN expression is associated with poor outcome and angiogenesis in invasive ductal carcinoma of the breast.

Loss of PTEN expression has been associated with advanced stages of tumor. Tumor angiogenesis is involved in tumor progression. In breast cancer, a high frequency of mutations of the PTEN locus has been reported. However, the prognostic importance of PTEN expression and its correlation with angiogenesis in breast cancer have not been well established. Formalin-fixed, paraffin-embedded tissues from 99 women with a primary diagnosis of invasive ductal carcinoma were evaluated for PTEN expression by immunohistochemical methods. The microvessel density (MVD) was also studied by immunohistochemical labeling of endothelial cells with CD34 antibody. Computerized image analysis was used to evaluate MVD. Reduced PTEN expression was seen in 27.3% of invasive ductal carcinoma. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). Reduced PTEN expression correlated with lymph node status (P < 0.01), tumor grade (P < 0.05), and tumor-node-metastasis (TNM) stage (P < 0.05). There was a statistically significant correlation between reduced PTEN expression and increased MVD (P < 0.05). The mean MVD was higher in reduced PTEN-expressive tumors, irrespective of stage, compared with normal PTEN-expressive tumors with the same stage. On multivariate analysis, only TNM stage and reduced PTEN expression correlated with survival. Our results suggest that reduced PTEN expression may be an independent prognostic indicator in patients with invasive ductal carcinoma. PTEN loss may be associated with increased tumor angiogenesis.     

Angiogenesis and lymphangiogenesis in sporadic hepatic angiomyolipoma

Angiogenesis and lymphangiogenesis are critical processes for tumor growth, invasion, and metastasis. The present study aimed to investigate the distribution and clinical significance of angiogenesis and lymphangiogenesis in hepatic angiomyolipoma (AML). We performed immunohistochemical staining for endothelial cell markers (CD34 and podoplanin) on 80 cases of sporadic hepatic AMLs. Microvessel density (MVD) and lymphatic vessel density (LVD) were determined in intratumoral and peritumoral regions and adjacent non-tumorous liver tissues. All hepatic AMLs showed positive staining for CD34 and podoplanin. Intratumoral and peritumoral MVDs and LVDs were significantly higher than those in adjacent liver tissues (P < 0.001). No statistical difference in both MVD and LVD was found between intratumoral and peritumoral areas. Large tumors (>5 cm) had a significantly increased MVD and LVD as compared with smaller tumors. A significant positive correlation was found between average LVDs and MVDs (r = 0.567, P < 0.001), and LVDs were a relatively lower event as compared with MVDs. Double immunostaining revealed that no neoplastic cells positive for HMB-45, an antibody reacting with melanosome-associated antigen, were concurrently immunoreactive for endothelial cell markers. In conclusion, intratumoral and peritumoral angiogenesis and lymphangiogenesis commonly occur in hepatic AMLs, thus representing potential therapeutic targets for this disease.     

整合素β3 mRNA表达与胃癌微血管密度、进展及预后的关系

目的　探讨整合素 β3mRNA在胃癌中的表达及其与肿瘤微血管密度 (MVD)、生长方式、浸润转移和预后的关系。方法　应用原位杂交和免疫组织化学技术 ,检测 10 5例胃癌组织中整合素 β3mRNA和CD3 4的表达。结果　整合素 β3mRNA在非肿瘤胃黏膜中的阳性表达率为 3 0 % (6/ 2 0 ) ,显著低于胃癌组 (61 0 % ,64/ 10 5,χ2 =8 85,P =0 0 3 7) ;在浸润性生长、T3 ～T4 期、有淋巴结转移和远处转移的病例中 ,阳性率分别为 70 2 % (40 / 57)、72 1% (44/ 61)、68 6% (48/ 70 )和 85 7% (3 6/ 42 ) ,均显著高于膨胀性生长 (χ2 =14 97,P =0 0 0 2 )、T1～T2 期 (χ2 =15 2 1,P =0 0 15)、无淋巴结转移 (χ2 =17 89,P =0 0 2 5)及无远处转移的病例 (χ2 =2 0 2 2 ,P =0 0 0 5;χ2 =2 1 3 5,P =0 0 3 5) ;同样 ,它们的平均MVD均显著高于膨胀性生长 (t =10 10 5,P =0 0 0 1)、T1～T2 期 (t=5 961,P =0 0 0 1)、无淋巴结转移 (t= 3 819,P =0 0 1)和无远处转移的病例 (t =10 578,P =0 0 0 1;t =7 882 ,P =0 0 0 1) ;阳性表达组的平均血管数 (41 0 2± 8 55)个 / 0 72mm2 明显高于阴性表达组的平均微血管数 (2 5 2 6± 11 2 5)个 / 0 72mm2 (t =11 2 5,P =0 0 2 5) ,两者之间呈显著正相关 (rs=0 3     

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p=0.008) and the presence of lymph node metastasis at the time of diagnosis (p=0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p<0.001) and in the disease-free survival among patients with tumors of the lower lip (p=0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.     

卵巢上皮肿瘤血管内皮生长因子受体3和CD31表达与肿瘤转移的研究

目的:研究卵巢肿瘤组织血管内皮生长因子受体3(VEGFR-3)和CD 31的表达与新生淋巴管和血管的生成及肿瘤转移的关系。方法: 采用免疫组织化学及图像分析方法,检测29例卵巢上皮癌和19例良性肿瘤组织中VEGFR-3 和CD31的表达,计数VEGFR-3阳性淋巴管数 (MLC) 和微脉管密度(MVD)。结果: 卵巢上皮癌MLC和MVD显著高于良性肿瘤和正常组织(MLC, P＜0.05; MVD, P＜0.01)。有淋巴转移的卵巢上皮癌患者MLC和MVD显著高于无淋巴转移患者(P＜0.05)。卵巢上皮癌临床分期Ⅲ-Ⅳ期患者的MLC和MVD显著高于Ⅰ-Ⅱ期(MLC,P＜0.05;MVD,P＜0.01)。卵巢上皮癌MLC和MVD在不同的组织学类型和组织学分级无显著差异(P＞0.05)。结论: 卵巢上皮肿瘤组织VEGFR-3和CD31的表达水平与肿瘤的转移密切相关;MLC和MVD提示肿瘤组织有淋巴管和血管的生成,可作为判断肿瘤转移的生物学指标。     

Association between focal adhesion kinase and matrix metalloproteinase-9 expression in prostate adenocarcinoma and their influence on the progression of prostatic adenocarcinoma

Focal adhesion kinase (FAK), a member of the non-receptor cytoplasmic tyrosine kinase family, is associated with the development and progression of cancer. Matrix metalloproteinase-9 (MMP-9) is directly involved in the degradation of the extracellular matrix, and basement membrane components promote cancer cell migration and invasion. There is a functional interaction among FAK, MMP-9 and vascular endothelial growth factor (VEGF), which leads to enhanced cancer angiogenesis, cancer cell invasion and progression of malignancy. FAK, MMP-9, VEGF and CD34-positive microvessel density (MVD) were examined in 100 patients with prostate adenocarcinoma using immunohistochemistry. The relationship among these proteins and their impact on angiogenesis and clinicopathological parameters were also evaluated. The FAK expression was found to be positively correlated with the Gleason score, WHO grade group, tumour stage, extracapsular extension and perineural invasion. The MMP-9 expression was positively correlated with the WHO grade group, tumour stage, extracapsular extension, positive surgical margin and lymphovascular and perineural invasion. The FAK expression was also positively correlated with MMP-9 expression and MVD. However, no correlation between FAK and VEGF expression was identified. The MMP-9 expression was positively correlated with FAK expression and MVD. Strong MMP-9 expression was associated with shorter disease-free survival. These results suggest that strong MMP-9 and FAK expressions play an essential role in the progression of prostate adenocarcinoma. Further investigations should be conducted to determine the importance of these proteins as therapeutic targets for patients with prostate adenocarcinomas.     

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining.

Microvascular density (MVD) is substantially increased in bone marrow biopsies of patients with chronic idiopathic myelofibrosis (CIMF). CD105, a useful molecule for assessing MVD in various malignancies, is preferentially expressed by recently formed microvessels. Increased serum-soluble CD105 in patients with chronic myeloproliferative disorders, including CIMF, was documented. CD105 MVD has not so far been investigated in CIMF: to this end, the results in 55 patients with CIMF and 21 controls were compared with the conventional CD34 immunostaining as well as traditional histological and clinical disease features. The MVD mean values estimated by both CD105 and CD34 were significantly higher in CIMF patients than in controls (P<0.00001). In addition, the proportion of CD105-positive megakaryocytes was significantly higher in CIMF than in controls (P<0.0001). A degree of reticulin fibrosis >2 correlated with increased CD105 MVD (P=0.05). A multivariate analysis confirmed that CD105-positive MVD was an independent adverse prognosticator. This study demonstrates that while MVD, as assessed by both CD34 and CD105 immunostaining, is significantly increased in CIMF, only CD105-determined MVD correlates with the degree of fibrosis and is prognostically relevant. These findings provide a rationale for the investigational use of anti-CD105-targeted drugs in CIMF.     

Expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and its correlation with angiogenesis in gastric cancer

Objective

To examine the expression of carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1) and CD34 in gastric adenocarcinoma, and to investigate their relations with clinical pathology-related factors.

Methods

Immunohistochemistry (IHC) was used to analyze the expression of CEACAM1 and CD34, and micro-vessel density (MVD) marked by CD34 was calculated in 208 cases of human gastric adenocarcinoma and in 56 cases of normal human gastric tissues.

Results

There was no expression of CEACAM1 in normal gastric mucosa. However, all of the gastric adenocarcinoma tissues expressed CEACAM1 with cytoplasmic and/or membranous staining. CEACAM1 expression was classified as high and low (137/208 vs. 71/208, 65.9% vs. 34.1%), the CD34-MVD value was significantly different between the two groups (P < 0.05). In addition, expressions of CEACAM1 and CD34 were significantly different from gastric adenocarcinoma to normal gastric tissues, respectively (P < 0.05). High CEACAM1 expression and high MVD value were positively associated with lymph nodes metastasis and TNM stage, but negatively related to pathological grade (P < 0.05). But they were irrelevant with tumor size, patients’ age and gender (P > 0.05).

Conclusions

The up-regulation of CEACAM1 expression may participate in tumorous angiogenesis, especially high expression of CEACAM1 promoted its capability of invasion and metastasis.