Mărgăritescu Cl, Simionescu Cristiana, Pirici D, Mogoantă L, Ciurea Raluca, Stepan A
Department of Pathology, Faculty of Dentistry, University of Medicine and Pharmacy of Craiova, Romania.
Rom J Morphol Embryol. 2008;49(4):447-58.
Tumors require a blood supply for growth and hematogenous dissemination. Angiogenesis is one of the mechanism by which tumors acquire their microcirculation. Structurally and functionally, these newborn vessels are abnormal, showing increased permeability, delayed maturation, and potential for rapid proliferation. Such vascular defects could be an explanation for the aggressivity of oral squamous cell carcinoma (OSCC). For these reason we studied the morphology of tumoral vessels in such tumors by using immunohistochemistry and immunofluorescence. Forty formalin-fixed, paraffin-embedded tissue blocks of OSCC were processed for double enzymatic and fluorescence immunohistochemistry. We were interested in analyzing the tumor vessel architecture, and their maturity and activity in such tumors. The tumor vessel architecture had a chaotic pattern, mostly of different sizes, aberrant morphology, tortuous, without clear lumen, and irregularly branches. Regarding pericytes recruitment, the immature and intermediate vessel types (both negative to smooth muscle actin-SMA) were the most numerous type of tumoral vessels. The mature ones (positive to SMA) were readily more numerous at the invasive front of OSCC (85.4 vessels/4 mm(2) +/- 38.3), especially in poor differentiated tumoral type. Investigation of the tumor vessel basal membrane, as reactivity for collagen IV, revealed variability in thickness (2.59 microm +/- 0.48), small surface projections, discontinuities and loose associations with endothelial cells; these abnormalities being more obviously at the tumor-host interface and in poor differentiated OSCC. The most active angiogenesis was noticed in poor differentiated OSCC (0.23 +/- 0.04), at the tumor-host interface with the immature and intermediated vessel as the most active tumor vessel types. In conclusion, our study revealed some peculiar structurally and functionally defects of tumor vessels in OSCC, changes that could be selective targets for the new developing antiangiogenic drugs.
肿瘤的生长和血行播散需要血液供应。血管生成是肿瘤获得微循环的机制之一。从结构和功能上看,这些新生血管是异常的,表现为通透性增加、成熟延迟以及快速增殖的潜力。这种血管缺陷可能解释了口腔鳞状细胞癌(OSCC)的侵袭性。基于这些原因,我们通过免疫组织化学和免疫荧光技术研究了此类肿瘤中肿瘤血管的形态。对40个福尔马林固定、石蜡包埋的OSCC组织块进行了双重酶促和荧光免疫组织化学处理。我们感兴趣的是分析此类肿瘤中肿瘤血管的结构、成熟度和活性。肿瘤血管结构呈现混乱模式,大多大小各异、形态异常、扭曲、无清晰管腔且分支不规则。关于周细胞募集,未成熟和中间型血管(平滑肌肌动蛋白 - SMA均为阴性)是肿瘤血管中数量最多的类型。成熟血管(SMA阳性)在OSCC的侵袭前沿数量更多(85.4条血管/4 mm²±38.3),尤其是在低分化肿瘤类型中。对肿瘤血管基底膜(以胶原蛋白IV反应性表示)的研究显示,其厚度存在差异(2.59微米±0.48),有小的表面突起、连续性中断以及与内皮细胞的松散连接;这些异常在肿瘤 - 宿主界面和低分化OSCC中更为明显。在低分化OSCC(0.23±0.04)中,在肿瘤 - 宿主界面观察到最活跃的血管生成,其中未成熟和中间型血管是最活跃的肿瘤血管类型。总之,我们的研究揭示了OSCC中肿瘤血管在结构和功能上的一些特殊缺陷,这些变化可能是新型抗血管生成药物的选择性靶点。