Fox S B, Leek R D, Weekes M P, Whitehouse R M, Gatter K C, Harris A L
Department of Cellular Science, University of Oxford, John Radcliffe Hospital, U.K.
J Pathol. 1995 Nov;177(3):275-83. doi: 10.1002/path.1711770310.
In some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel 'hot spots' has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the 'hot spots' assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity. A Chalkley count was also performed on a further 211 invasive breast carcinomas. Significant correlations were observed between manual microvessel density and luminal perimeter (r = 0.6, P = 0.0004), luminal area (r = 0.56, P = 0.002), and microvessel number (r = 0.57, P = 0.0009) by computerized analysis. There were also significant correlations between the microscopic hot spots of 0.155 mm2 and 0.848 mm2 for microvessel number (r = 0.81, P < 0.00005), luminal perimeter (r = 0.78, P < 0.00005), and luminal area (r = 0.65, P = 0.0001). In addition, a significant correlation was observed between microvessel density and both subjective vascular grade (P = 0.002) and Chalkley count (P = 0.0001). A significant reduction in overall survival was observed between patients stratified by Chalkley count in both a univariate (P = 0.02) and a multivariate (P = 0.05) analysis in the 211 invasive breast carcinomas. These findings show that Chalkley counting is a rapid method of quantifying tumour angiogenesis and gives independent prognostic information which might be useful in diagnostic practice.
在一些乳腺癌研究中，免疫组化突出显示的微血管“热点”定量已被证明是一种强大的预后工具。然而，不同研究中使用的抗体、评估的“热点”数量和大小，以及将患者分为高血管组和低血管组的分层方法各不相同。此外，对于微血管密度与其他血管参数之间的关系知之甚少。这些不确定性以及该技术的繁琐性质使其不适用于诊断实践。本研究使用手动和计算机图像分析技术，在30例浸润性乳腺癌的初步系列研究中，检查不同大小显微镜视野下微血管密度与血管参数之间的关系。免疫组化染色的自动像素分析、Chalkley点计数和观察者主观血管分级也作为测量肿瘤血管生成的更快方法进行了评估。还对另外211例浸润性乳腺癌进行了Chalkley计数。通过计算机分析观察到手动微血管密度与管腔周长（r = 0.6，P = 0.0004）、管腔面积（r = 0.56，P = 0.002）和微血管数量（r = 0.57，P = 0.0009）之间存在显著相关性。对于微血管数量（r = 0.81，P < 0.00005）、管腔周长（r = 0.78，P < 0.00005）和管腔面积（r = 0.65，P = 0.0001），在0.155平方毫米和0.848平方毫米的显微镜热点之间也存在显著相关性。此外，观察到微血管密度与主观血管分级（P = 0.002）和Chalkley计数（P = 0.0001）之间存在显著相关性。在211例浸润性乳腺癌的单变量（P = 0.02）和多变量（P = 0.05）分析中，按Chalkley计数分层的患者之间观察到总生存率显著降低。这些发现表明，Chalkley计数是一种快速量化肿瘤血管生成的方法，并提供独立的预后信息，这可能在诊断实践中有用。
