Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast

Abstract

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34 + and CD31 + vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34 + and CD141 + vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34 + and CD141 + vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions.

Expression patterns of angiogenic and lymphangiogenic factors in ductal breast carcinoma in situ

“…Several explanations are feasible for this rather unexpected finding: Our data, demonstrating quantitative differences between expression of angiogenic factors, suggest a biological difference among the groups of (a) pure DCIS and (b) DCIS with concomitant invasive carcinoma. This is consistent with findings from Teo et al (2002) describing a different vascular density and phenotype in pure DCIS vs DCIS associated with invasive carcinoma, the latter showing significantly greater numbers of CD34 þ and CD141 þ vessels and fewer staining for FVIII (Teo et al, 2002). Besides distinct vascular profiles in pure and coexistent DCIS, that study also showed a significant negative correlation between vascular density and the extent of necrosis of the tumour, and a correlation between vascular density and the nuclear grade was noted, being highest in the intermediate grade DCIS (Teo et al, 2002).…”

“…This is consistent with findings from Teo et al (2002) describing a different vascular density and phenotype in pure DCIS vs DCIS associated with invasive carcinoma, the latter showing significantly greater numbers of CD34 þ and CD141 þ vessels and fewer staining for FVIII (Teo et al, 2002). Besides distinct vascular profiles in pure and coexistent DCIS, that study also showed a significant negative correlation between vascular density and the extent of necrosis of the tumour, and a correlation between vascular density and the nuclear grade was noted, being highest in the intermediate grade DCIS (Teo et al, 2002). The latter is also in agreement with our observation that the association of the proangiogenic growth factors and receptors with pure DCIS was considerably more pronounced in the subgroup of non-high-grade DCIS as compared with high-grade DCIS.…”

Predictors of disease progression in ductal carcinoma in situ of the breast and vascular patterns

“…Vascular breaks were classified as demonstrating type "A" vascular breaks (blood vessel growing into but not completely through a duct), type "B" vascular breaks (blood vessel completely transecting a duct into unequal parts), or both. Stromal microvessel density was calculated on 5 randomly selected low-grade DCIS cases and 5 randomly selected high-grade cases with criteria adapted from Teo et al [11] (see Fig. 2 for examples of types of vascular patterns).…”

“…However, there are conflicting data regarding the difference in angiogenesis in low-, intermediate-, and highgrade DCIS. Some studies demonstrated significant differences in vascular density and expression of regulators of angiogenesis among different grades of DCIS [8][9][10][11], whereas others were unable to demonstrate a significant difference using similar approaches [7].…”

Perfusion systems that minimize vascular volume fraction in engineered tissues

“…This value is greater than the 1%-5% vascular volume fractions observed in vivo for many tissues. [25][26][27] Thus, whether optimal designs based on a parallel array of vessels are appropriate for an engineered tissue will depend on how the magnitude of the vascular fraction affects the design objective. For instance, having a large fraction of a tissue consist of open vessels may compromise the mechanical stability of the tissue.…”