HMGB1与胃癌组织血管形成的关系及其临床意义

目的 确定高迁移率族蛋白B1与胃癌组织血管生成之间的联系,筛选胃癌诊断和治疗的靶点。方法 收集2008年6月~2016年6月怀化市第一人民医院病理科正常胃、胃癌旁、胃癌癌组织蜡块共105例,采用常规HE染色（苏木素-伊红）、免疫组织化学染色（链霉菌抗生物素蛋白-过氧化物酶连结法-SP法）,检测正常胃组织、胃癌旁组织及胃癌组织中HMGB1的表达情况、检测人造血祖细胞抗原（CD34）的表达情况来反映正常胃组织、胃癌旁组织及胃癌组织中的微血管密度（MVD）,统计学分析HMGB1的表达与胃癌组织MVD之间存在的相关性。结果 正常胃组织HMGB1的阳性表达率低,胃癌癌旁组织HMGB1的阳性表达率增高、胃癌组织中HMGB1的阳性表达率最高,在三种组织中HMGB1的表达存在差异（P＜0.05）;HMGB1的表达水平与MVD表现出正相关性（r=0.205,P＜0.05）。结论 HMGB1在胃组织、胃癌旁组织、胃癌组织中的表达呈阶梯型增高,胃癌组织中HMGB1的表达水平与组织MVD成正相关性。     

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.     

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.     

CD24,ALCAM在大肠癌的表达及其临床意义

目的:探讨CD24,ALCAM 在大肠癌中的表达及其与细胞增殖、血管生成的关系。方法:运用免疫组织化学检测66例大肠癌肿瘤组织CD24,ALCAM,CD34,PCNA 的表达情况,根据CD34 的染色情况计算出大肠癌组织的微血管密度（microvessel density, MVD）,根据PCNA染色情况计算出肿瘤细胞PCNA标记指数。结果：免疫组织化学染色显示正常大肠黏膜CD24,ALCAM 绝大部分呈阴性染色,超过75%的大肠癌细胞有不同程度的CD24 染色。44%的肿瘤CD24 呈中等强度表达,26%的肿瘤呈强阳性表达。 高Dukes分期、高pTNM分期及有淋巴结转移、浆膜外浸润的癌组织中CD24 蛋白染色强度显著高于对应组（P＜0.01)。68% 的大肠癌细胞有不同程度的ALCAM 染色。ALCAM 表达与浸润深度、pTNM分期,淋巴结转移明显正相关。在CD24,ALCAM 阳性表达病例中,PCNA 的表达随着CD24 表达强度的升高而升高（P＜0.05）。大肠癌CD24 蛋白表达强度与大肠癌微血管密度轻度相关（r=0.228,P=0.019）。大肠癌ALCAM 蛋白质表达与MVD无关（P=0.17）。结论：CD24,ALCAM 可能在大肠癌发生发展中起重要作用。     

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.     

乳腺癌中CD105表达及相关因素分析

目的 多项免疫组化（multiple immunohistoehemistry,MIHC）检测内皮因子CD105作为判断患者乳腺癌生物学行为及预后指标的可能性。方法 选取2003年11月-2004年1月经河北医科大学病理科确诊为原发性乳腺癌患者石蜡包埋组织标本87例,癌旁组织标本20例,同期乳腺良性病变标本24例。以CD105单克隆抗体为标记物进行免疫组化染色,根据CD105的表达水平计测微血管密度（mierovessel density,MVD）。结果CD105所标记的MVD在乳腺癌组织和乳腺良性病变以及乳腺良性病变与癌旁组织之间的表达差异均有显著性（P＜0．05）,癌旁组织中CD105几乎表达缺失;淋巴结转移阳性、组织分化差（Ⅲ级）、临床TNM分期晚以及VEGF表达阳性、ER、PR表达阴性的患者中,CD105的表达明显升高,差异均有显著性（P＜0．05）。结论 CD105主要在处于增殖状态的血管内皮细胞上表达,在标记肿瘤组织活性微血管方面特异性极高,是检测乳腺癌患者预后的重要指标。     

人肝癌组织中CD34和血管内皮生长因子的表达及微血管密度的 …

目的 探讨ＣＤ３４和血管内皮生长因子（ＶＥＧＦ）在人肝癌组织中的表达及微血管密度（ＭＶＤ）的病理意义。方法 对３０例人肝细胞肝癌９ＨＣＣ）及相应癌旁组织,１０例肝硬化,５例轻度慢性肝炎和４例正常肝组织,进行了ＣＤ３４、ＶＥＧＦ免疫组织化学ＳＰ法检测,对ＣＤ３４阳性血管进行ＭＶＤ计数,对ＶＥＧＦ进行半定量计数,并结合肝癌的病理特征进行分析。结果 ＨＣＣ组织中ＣＤ３４呈广泛,窦隙状阳性表达,而在正常及     

Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis

Microvessel density (MVD), an indicator of angiogenesis, has been proposed to predict prognosis of patients with renal cell carcinoma (RCC), but its ability to predict survival of patients with RCC remains controversial. The present study sought to address this question rigorously by systematically reviewing the literature on MVD and RCC prognosis. We identified relevant studies in PubMed, EMBASE and the Cochrane Library, and two reviewers independently assessed study quality and extracted relevant data to compare survival based on MVD stratification in patients with RCC. We identified 15 studies that satisfied the inclusion criteria; eight studies assessed MVD in surgical samples by immunohistochemistry to label factor VIII; four studies, by immunohistochemistry to label CD34; two studies, CD31; and one study, CD105. Survival meta-analysis was performed using data pooled from 10 studies: five based on factor VIII, two based on CD34, two based on CD31 and one based on CD105. The overall survival hazard ratio describing the relationship between MVD and survival in all 10 pooled studies was 0.964 (95% CI: 0.873-1.065), while the individual hazard ratios for pooled studies based on factor VIII were 1.673 (95% CI: 0.860-3.252); CD34, 0.903 (95% CI: 0.853-0.956); and CD31, 0.926 (95% CI: 0.868-0.989). The corresponding result for the sole trial based on CD105 was 0.1759 (95% CI: 0.036-0.856). These findings suggest that MVD is not reliably associated with survival time of patients with RCC, which may reflect the need to take into account whether the microvasculature is differentiated or not. MVD as currently calculated may not be an ideal prognostic factor for patients with RCC.     

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.     

CD105在胃癌组织中的表达及其临床意义

目的通过检测胃癌组织中CD105的表达,研究其临床意义。方法收集32例经病理确诊的胃癌组织标本,采用组织芯片技术制片后进行免疫组织化学染色,再运用图像分析方法对各类胃癌组织中的CD105表达进行相对定量,并以此分析CD105表达的临床意义。结果 CD105在胃癌边缘、浸润组织中呈高表达,且进展期胃癌组织中的CD105表达显著升高（P〈0.05）;CD105表达程度高则胃癌浸润程度高、转移性强、预后差。结论胃癌组织中CD105的表达升高,且其表达水平高低与其转移情况和Dukes分期有关,有助于推测预后情况。     

CD105 is a more appropriate marker for evaluating angiogenesis in urothelial cancer of the upper urinary tract than CD31 or CD34

Angiogenesis plays an important role in cancer progression in many types of cancer. Evaluation of angiogenesis is often performed, but the optimal methodology for human cancer has not been agreed upon. As adequate evaluation of angiogenesis in cancer tissues might be important for prediction of prognosis and treatment decisions, we evaluated angiogenesis semiquantitatively by assessing microvessel density (MVD) in urothelial cancer of the upper urinary tract (UC-UUT). We compared the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 122 patients diagnosed with UC-UUT without metastasis. Vascular endothelial growth factor (VEGF)-A expression was also evaluated immunohistochemically. Correlations between MVD with each marker and pT stage, grade, survival, and VEGF-A expression were investigated. Mean (standard deviation) MVD as estimated by immunohistochemical staining with anti-CD31, anti-CD34, and anti-CD105 were 47.1 (17.9)/high-power field (HPF), 70.9 (19.5)/HPF, and 31.2 (16.7)/HPF, respectively. Although all MVDs were significantly associated with pT stage and grade, CD105-MVD showed the strongest association. Similarly, CD105-MVD showed the strongest correlation with VEGF-A expression (r?=?0.530, p?<?0.001). Although all MVDs were associated with metastasis-free survival and cause-specific survival on univariate analysis, only CD105-MVD was retained as an independent predictor in multivariate analysis including pT stage and grade. CD105-MVD may be the preferred marker for semiquantitative assessment of angiogenesis in patients with UC-UUT.     

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.     

Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease-free survival

Marioni G, Marino F, Blandamura S, D’Alessandro E, Giacomelli L, Guzzardo V, Lionello M, de Filippis C & Staffieri A
(2010) Histopathology 57 , 535–543
Neoangiogenesis in laryngeal carcinoma: angiogenin and CD105 expression is related to carcinoma recurrence rate and disease‐free survival Aims: Angiogenin regulates angiogenesis supporting primary and metastatic tumour growth. CD105 is a proliferation‐associated protein expressed in angiogenic endothelial cells. The aim of this study was to investigate for the first time angiogenin expression in laryngeal squamous cell carcinoma (LSCC) and to evaluate the relationship between angiogenin and CD105 expression, clinicopathological and prognostic parameters. Methods and results: A total of 108 consecutive operable LSCCs were studied. Angiogenin expression was determined immunohistochemically in both carcinoma cells and intratumoral vessels. CD105 expression was evaluated in endothelial cells of LSCC and calculated by a computer‐based image analysis system. The percentage of the fields occupied by CD105‐assessed microvessels was determined. Angiogenin expression in carcinoma cells was higher in LSCC patients who experienced loco‐regional recurrence of disease (P = 0.032). Disease‐free survival (DFS) was shorter in cases with carcinoma cells showing angiogenin expression >21.0% (P = 0.035). Angiogenin expression in carcinoma cells was correlated strongly with the angiogenin score in endothelial cells of intratumoral vessels (P = 0.0000). Higher loco‐regional carcinoma recurrence rate and shorter DFS in patients with high CD105 expression were found (P = 0.0004, P = 0.0001). Conclusions: Angiogenin expression in laryngeal carcinoma cells and CD105 expression can be considered as potentially useful to detect LSCC patients with higher risk of disease recurrence who might benefit from more aggressive therapy.     

Gastric neuroendocrine cell hyperplasia and type 1 tumours occurring within gastric hyperplastic polyps

We wish to highlight the unusual occurrence of gastric neuroendocrine cell hyperplasia and type I neuroendocrine tumours within three hyperplastic polyps. In all cases, the neuroendocrine component was present within and between the hyperplastic foveolar glands of the polyps and overall formed the minor part of the polyps. Two of the patients presented with epigastric pain and the other with fatigue from anaemia, and on endoscopy, all three were found to have superficially ulcerated gastric polyps in the body (cases 1 and 2) and fundus (case 3). Two of the cases had serologically proven autoimmune atrophic gastritis, while the third case had histological evidence of an atrophic gastritis, most likely also autoimmune in aetiology. Cases 1 and 3 had single hyperplastic polyps, while case 2 had three polyps. All polyps showed linear neuroendocrine cell hyperplasia within hyperplastic foveolar epithelium both at the surface and within deeper-situated glands. Neuroendocrine immunohistochemistry highlighted the neuroendocrine cell hyperplasia. The bulk of the neuroendocrine component was restricted to hyperplastic mucosa forming the polyps. Non-hyperplastic adjacent mucosa showed less prominent neuroendocrine cell hyperplasia. It is unclear whether the two pathologies occurred simultaneously or independently. The common feature and causal link is atrophic gastritis, which predisposed the gastric mucosa to the development of both neuroendocrine cell hyperplasia and tumours, and hyperplastic polyps.     

Why is the hyperplastic polyp a marker for the precancerous condition of the gastric mucosa?

It is well known from the older literature that gastric carcinomas are more likely to develop in a stomach containing hyperplastic polyps. The reason why such a stomach should represent a precancerous condition is, however, largely unexplained. The aim of this study was to determine the disorders of the gastric mucosa in which hyperplastic polyps occur. In 244 patients with hyperplastic polyp, in whom at least two additional biopsies each from the antrum and corpus were available, gastritis was classified on the basis of the updated Sydney System. In none of the 244 patients was the gastric mucosa found to be normal. The most common disorder, at 51.3%, was autoimmune gastritis of the corpus mucosa, while chronic active Helicobacter pylori (Hp) gastritis was seen in 37.3% of the patients. Of the patients with Hp gastritis, 56.1% had corpus-dominant Hp gastritis. Other forms were relatively rare: when A-gastritis, corpus-dominant Hp gastritis and any other form of Hp gastritis were lumped together as a precancerous condition, these changes were found in 88.6% of the patients with hyperplastic polyps of the stomach. In the presence of hyperplastic polyps of the gastric mucosa, additional biopsies obtained from the antrum and corpus should always be performed to obtain a basis for deciding whether to apply Hp eradication treatment as potential carcinoma prophylaxis.     

Angiogenesis in craniopharyngiomas: Microvascular density and tissue expression of the vascular endothelial growth factor (VEGF) and endostatin

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine abnormality and often locally aggressive. Several studies have demonstrated that angiogenesis or neovascularization plays an important role in tumoral growth. The microvascular density (MVD) of craniopharyngiomas was determined in tumor tissue samples from a reference neurosurgery center located in southern Brazil using immunohistochemical methods for two endothelial markers, CD34 and CD105 (endoglin). In addition, tissue expression was determined for an angiogenesis stimulatory factor and for one of its inhibitors, the vascular endothelial growth factor (VEGF) and endostatin, respectively. Endothelial cell immunoreactivity for CD34 and CD105 was observed scattered within the stroma. MVD determined using CD105 antigen was significantly lower than the results obtained by using CD34 antigen. There was no association between the two endothelial markers and tumor extension. The epithelial component showed different degrees of immunoreactivity for VEGF and endostatin in all samples analyzed. We were not able to establish a relationship between angiogenesis in craniopharyngiomas and tumor extension with the endothelial markers used in this study. The investigated vascularization stimulatory and inhibitory factors showed no relation with MVD. We believe that CD105 antigen can be a more specific endothelial marker for tumor angiogenesis than CD34 antigen.     

Microvessel density and the association with single nucleotide polymorphisms of the vascular endothelial growth factor receptor 2 in patients with colorectal cancer

The measurement of microvessel density (MVD) is a widely accepted method for assessing the neoangiogenetic activity in neoplasia. The aim of the present study was to compare MVD with single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 genes and, furthermore, with quantitative measurements of the receptors in colorectal cancer (CRC) tissue. Prognosis was also assessed. Blood and tissue were collected from 110 patients surgically resected for CRC. SNPs were analysed from genomic DNA by polymerase chain reaction. MVD was assessed by immunohistochemistry using CD34 and CD105 combined with caldesmon in order to identify also immature vessels. Microvessels were counted in three fields of vision, and the mean MVD was used for statistical analysis. The VEGFR-2 1192 C/T and −604 T/C SNPs were associated with the MVD assessed by CD105. The median MVD score for the 1192 CC genotype was significantly lower compared to the CT + TT genotypes (p = 0.002). The median MVD score for the −604 CC genotype was significantly higher compared to the TT + TC genotypes (p = 0.009). A possible association, although non-significant, was demonstrated for the CD34-positive microvessels. The 1192 CC genotype and the −604 TT + TC genotypes correlated with improved survival. This is the first report on correlations between SNPs in the VEGF receptor genes and MVD in patients with CRC. Associations were shown between two SNPs in the VEGFR-2 gene and the CD105-positive microvessels indicating an impact on neoangiogenesis. Moreover, an association between the SNPs and survival was demonstrated. The clinical implications of these findings need further investigations.     

CD34及CD105两种微血管标记物在瘢痕微血管构筑中的比较

背景：在瘢痕微血管构筑研究中,目前尚无可靠的瘢痕新生血管标记物。CD34和CD105是目前常用来标记微血管密度的一种方法,但两者又有各自特点。 目的：比较CD34、CD105两种微血管标记物在病理性瘢痕微血管构筑方面的特征差异。 方法：采用免疫组化的方法检测人正常皮肤、非病理性瘢痕、增生性瘢痕和瘢痕疙瘩内CD34、CD105的表达,采用图像分析软件测量阳性染色的微血管的内径、表达面积并分析以CD34、CD105标记的微血管的形态、分布特征。 结果与结论：在所有标本内,CD34标记的微血管较为成熟,多表现为分支状、肝窦状及芽孢状,微血管内径平均值为(73.14±13.81) μm;CD105标记的微血管较为幼稚,多表现为圆形或镶嵌状,部分无管腔,微血管内径平均值为(27.91±5.86) μm。作为微血管标记物,CD105在标记瘢痕新生血管方面优于CD34,CD105可视作瘢痕新生血管可靠的标记物。     

Role of PTEN and MMP-7 expression in growth, invasion, metastasis and angiogenesis of gastric carcinoma

To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry. Microvessel density (MVD) was counted using the anti-CD34 antibody. The expressions of PTEN and MMP-7, and MVD were compared with the clinicopathological parameters of tumors, and the relationship between PTEN and MMP-7 expression and MVD was analyzed. It was found that PTEN was expressed less frequently in primary gastric carcinoma cells than in adjacent epithelial cells (P < 0.05), whereas this was reversed for MMP-7 (P < 0.05). PTEN expression was negatively correlated with invasion, metastasis, growth pattern, Lauren's classification and histological classification (P < 0.05). Matrix metalloproteinase-7 expression was positively associated with tumor size, Borrmann's classification, invasive depth, metastasis and TNM staging (P < 0.05), but negative with PTEN expression (P < 0.05). A positive correlation of MVD with tumor size, invasive depth, metastasis and TNM staging was found (P < 0.05). Microvessel density depended on decreased PTEN expression and increased MMP-7 expression (P < 0.05). The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. Close correlation between PTEN on MMP-7 expression provided a novel insight into the regulatory effects of PTEN on MMP-7 expression in gastric carcinoma.     

Automated immunofluorescence analysis defines microvessel area as a prognostic parameter in clear cell renal cell cancer

Microvessel density (MVD) has been reported to have prognostic relevance for clear cell renal cell carcinoma (ccRCC). However, this finding is controversial because of the difficulty of MVD evaluation in this complex vascularized tumor type. The present study evaluates the use of an automated quantitative analysis (AQUA) system for objective and reproducible determination of tumor vascularization in clear cell renal cell carcinoma (ccRCC). The AQUA system was applied to tissue microarrays with 284 primary ccRCC tumors. To determine angiogenesis in ccRCC, we created an epithelial/stromal mask consisting of CD10, epithelial membrane antigen, and vimentin to distinguish epithelial tumor cells from CD34-positive endothelial cells. Using immunofluorescence and computer-aided quantification of CD34 expression, we measured the relative microvessel area (MVA) and compared the MVA to the manually counted MVD. The MVA determined by AQUA in a test set with 209 ccRCCs ranged from 0% to 30.3% (mean +/- SD, 10.1% +/- 6.3%). The manually determined MVD ranged from 6 to 987 vessels/mm(2) (416.8 +/- 252.8 vessels/mm(2)). MVA and MVD were significantly correlated (P < .001). A larger MVA was associated with histologic grade (P < .001), tumor stage (P =.008), presence of metastasis (P = .005), presence of sarcomatoid areas (P < .001), and tumor-specific survival (P < .001). Using MVA as defined in the test set, all associations with clinical and pathologic parameters were confirmed in a second independent validation set. MVA determination by AQUA is an objective and reliable method to quantify tumor vascularization in ccRCC. A large MVA correlates with a high MVD and is associated with better patient prognosis.