Endothelium originated from colorectal cancer stem cells constitute cancer blood vessels

Tumor growth depends on the formation of blood vessels that provide the supply of nutrients and oxygen. Previous data have shown that glioblastoma stem cells are able to give rise to vascular cells to constitute the functional vessels in tumor tissues. However, which kinds of vascular cells are generated from glioblastoma stem cells is largely debated. In addition, there is little evidence showing that the stem cells from other kinds of tumors can produce vascular cells to constitute the functional blood vessels in tumor tissues. Here we show that cancer stem cells of human colorectal carcinomas (CoCSC) can give rise to vascular endothelial cells and compose the vasculatures in cancer tissues. The human‐cell‐specific nuclear antigen NuMA⁺ vascular endothelial cells were detected in the blood vessels in xenografts derived from CoCSC. NuMA⁺ endothelial cells incorporated into functional blood vessels. Our data indicate that the cancer stem cells derived from human colorectal carcinomas have the capacity to generate functional blood vessels and provide a new mechanism for tumor vasculogenesis in carcinoma.     

Death of T cell precursors in the human thymus: a role for CD38

Thymic T cell maturation depends on interactions between thymocytes and cells of epithelial and hematopoietic lineages that control a selective process whereby developing T cells with inappropriate or self-reactive receptors die. Molecules involved in this process are the TCR expressed on thymocytes together with the CD3 complex and MHC-peptide on accessory cells. However, other molecules may favor or prevent death of thymocytes, thus playing a role in selection. CD38 is expressed by the majority of human thymocytes, mainly at the double-positive (DP) stage. In contrast, CD38 is not found on subcapsular double-negative (DN) thymocytes and on a proportion of medullary single-positive (SP) thymocytes. CD38 enhances death of thymocytes when it is cross-linked by goat anti-mouse (GAM) antiserum or by one of its ligands, CD31, expressed by thymic epithelial cells or transfected into murine fibroblasts (L cells). As most thymocytes are at an intermediate (DP) stage of development, it is likely that these cells are most vulnerable to death mediated via MHC-peptide-TCR interactions that is increased by CD38 cross-linking. DN and SP thymocytes are refractory to CD38-induced apoptosis. Accessory molecules, e.g. CD38, are expressed during thymic cell maturation and their presence is relevant for the survival or death of DP T cells in the course of selection. Based on our data, CD38 enhances thymocyte death by interacting with CD31 expressed by accessory cells. In addition, CD28 expression on developing thymocytes also appears to play a role for their selection and it synergizes with CD38 to induce apoptosis of DP thymocytes.     

Correlation between angiogenesis and reduction ratio measured using<Superscript>201</Superscript>Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma

OBJECTIVE: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using 201Tl single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC). METHODS: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre- an post-treatment, reduction ratio) and prognosis. RESULTS: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence. CONCLUSIONS: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of 201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.     

CD34、CD31与FⅧ显示非小细胞肺癌微血管密度的对比研究

目的探讨血管内皮标记物CD31、CD34与FⅧ在显示非小细胞肺癌(NSCLC)微血管密度(MVD)中的差异,以及MVD与淋巴结转移的关系.方法采用微波免疫组化染色方法(LSAB)检测CD31、CD34与FⅧ在78例NSCLS中的表达.结果 3种血管内皮标记物CD34、CD31与FⅧ显示的MVD分别是(65.8±14.3)条、(63.5±17.9)条和(54.3±19.4)条,范围分别是18～112条、16～102条和16～103条,3种微血管内皮标记物显示的MVD具有一致性(P＞0.05).CD34、CD31与FⅧ3种微血管内皮标记物显示NSCLC的MVD,在转移组分别是(69.5±15.7)、(65.3±14.5)和(58.3±16.3),在无转移组分别是(44.3±14.3)、(40.5±12.6)和(36.5±15.8),转移组与无转移组间均有非常显著的差异性(P＜0.01),而三种微血管内皮标记物之间显示的MVD无显著差异(P＞0.05).结论 CD34、CD31、FⅧ相关抗原均能清晰地、选择性地显示NSCLC的MVD,但CD34比CD31、FⅧ因子相关抗原更敏感,能突出显示较小的、不成熟的微血管或单一的内皮细胞;NSCLC的MVD与微血管内皮标记物的种类无关,与有无转移密切相关,MVD可作为预测NSCLC病人预后的指标.     

Histopathological analysis of the association between mucosal epithelial changes and the lamina propria vascular network in irritation fibroma

ObjectivesIrritation fibroma in the oral cavity causes atrophy or squamous epithelium thickening with respect to external injury-associated factors. However, ulcers do not occur in most cases. This study aimed to elucidate the mechanism by which ulcers do not form, focusing on the vascular network in the mucosal epithelium of irritation fibroma.MethodsImmunostaining was performed using an enzyme antibody method with primary antibodies against CD31 and Ki-67 in 17 cases of irritation fibroma in the buccal mucosa. One section was taken at three points from the margin and three points from just above the lesion for measurement. The number of blood vessels in the superficial and deep lamina propria at the measurement site were determined, and the area per blood vessel was measured.ResultsThe number and area of blood vessels in the superficial lamina propria just below the lesion epithelium were smaller than those in the margin. No difference was observed in the number and area of blood vessels in the deep lamina propria between the margins and lesions.ConclusionsOur results suggest that the vascular network in the deep lamina propria is maintained and compensates for the nutrient supply to the covering epithelium.     

Case of solitary pulmonary capillary hemangioma: Pathological features based on frozen section analysis

Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that must be distinguished from small and early lung cancers. Here, we report a case of SPCH for which we performed frozen section diagnosis. The patient was a 55‐year‐old Japanese woman. Five years before the operation, mixed ground‐glass opacity was detected by computed tomography in the left posterior basal segment of the lower lobe (S10). Because the interior tumor density of the ground‐glass opacity increased slightly, video‐assisted thoracic surgery wedge resection was performed. Frozen section diagnosis revealed a benign tumor without proliferation of atypical epithelial cells. The tumor had narrow alveolar lumens, thickened alveolar septa and a clear boundary separating it from normal lung tissue. The proliferated lumens varied in size and were lined with single layers of flat cells. After the operation, immunohistochemical staining of a paraffin section revealed that the thickened alveolar septa resulted from the proliferation of capillary vessels, the flat cells of which were positive for CD31 and CD34 and negative for podoplanin; the tumor was diagnosed as SPCH. Here, we discuss the pathological features of SPCH on frozen sections with reference to this case and review previous related reports.     

Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanoma

Malignant melanoma of the skin preferentially metastasises via the lymphatic system. Novel molecular biomarkers, which are involved in malignant transformation, proliferation, angiogenesis and lymphangiogenesis, are currently under investigation to elucidate the risk for lymph node metastasis. To this end, the vascular endothelial growth factors VEGF-C and VEGF-D have been identified to promote lymphangiogenesis and lymphatic spread through activation of its receptor, Vascular endothelial growth factor receptor-3 (VEGFR-3). Prompted by this assumption, we estimated the degree of lymphangiogenesis by semiquantitative immunohistochemical analysis of the expression of VEGFR-3 and the panvascular marker CD31 in primary cutaneous melanoma (n=26) and correlated these findings with the sentinel lymph node (SLN) status. The cohort was selected for matched prognostic markers in SLN-positive and SLN-negative patients. In contrast to other studies, we observed an inverse correlation between expression of these markers with lymph node metastases. Additionally, no difference between intratumoral versus peritumoral CD31- or VEGFR-3 expression on blood vessels versus lymphatic capillaries could be detected. Interestingly, VEGFR-3 upregulation was not restrained to vascular structures but also appeared on tumor cells. In summary, in our series VEGFR-3/CD31 immunohistochemical staining of primary melanoma does not serve as a valid marker to predict lymph node involvement. As lymphatic spread is a complex, multi-step process, several different biomarkers have to be combined to define new prognostic subgroups in cutaneous melanoma.     

人静脉移植物中MCP-1的表达

目的：探讨人静脉移植物中单核细胞趋化蛋白-1（MCP-1）的表达及其与巨噬细胞浸润的关系。方法：应用免疫荧光组织化学技术对30个静脉移植物再塞标本中MCP-1、CD68（巨噬细胞的标记物）、CD3l（内皮细胞的标记物）的表达进行了检测，用激光共聚焦显微镜拍片，图片用Silicon Graphics Octane进行处理。结果：在正常静脉血管中，MCP-1表达很弱；外膜中有少量CD68免疫阳性细胞，中膜和内膜中少见；CD31免疫阳性细胞仅在血管腔内皮细胞和外膜小血管中可见。在病变静脉血管，MCP-1在内皮细胞、平滑肌细胞中的表达呈强阳性；CD68免疫阳性细胞在外膜、中膜和内膜均可见到；CD31免疫阳性细胞不仅出现在血管腔内皮细胞和外膜小血管内皮细胞，且在中膜小血管内皮细胞也大量出现。免疫双重染色显示内皮细胞和巨噬细胞均表达MCP-1。结论：人静脉移植物MCP-1的表达上调，且和巨噬细胞的浸润关系密切，提示MCP-l对静物移植物炎症细胞的浸润及新内膜的形成有非常重要的作用。     

VEGF和CD31在皮肤鳞癌中的表达

目的 观察皮肤鳞癌(SSCC)中血管内皮生长因子(VEGF)和内皮细胞黏附分子(CD31)的表达,研究其与皮肤鳞癌发展的关系.方法 采用免疫组化染色法检测正常皮肤组织及鳞癌组织中VEGF和CD31的表达变化.结果 在正常组织中,VEGF和CD31表达低于鳞癌皮损组织,在Ⅲ~Ⅳ期鳞癌中的表达明显高于Ⅰ～Ⅱ期鳞癌中的表达(P<0.05).结论 VEGF及CD31蛋白的异常表达在皮肤鳞癌的进展过程中发挥重要作用.     

Peritumoural vascular invasion: a major determinant of triple-negative breast cancer outcome

Purpose

Triple-negative breast cancers (TNBC) have the worst outcome of all breast cancer subtypes. Nevertheless TNBC are heterogeneous in terms of pathological, biological and prognostic behaviours. We explored clinical and pathological factors correlated with outcome in this phenotype.

Methods

We retrospectively studied clinical and pathological factors correlated with prognosis in a series of 344 early TNBC. Staining for blood (CD31) and lymphatic (Podoplanin) vascular endothelium markers was performed to best characterise peritumoural vascular invasion (PVI) in 108 cases available for pathological reviewing.

Results

Univariate and multivariate analyses performed on our whole cohort underlined PVI as an independent predictive factor of distant metastasis (p = 0.00012, HR = 2.72 [1.63-4.52]). Standardised pathological reviewing of 101 histologically confirmed TNBC showed that PVI, observed in 41% (28% by haematoxylin and eosin staining plus 13% by immunohistochemistry), was confirmed as the first prognostic factor in TNBC, particularly in node-negative tumours. Five-year metastasis-free survival in this subset was 87.5% and 50.8% without and with PVI, respectively (p = 0.003).

Conclusions

Vascular invasion diagnosis is improved by the combination of HES and IHC. Moreover it is a major prognostic feature and must take a greater part in therapeutic management of early TNBC with the possibility to adapt the adjuvant treatment according to the predicted relapse risk.