Rosen's Breast Pathology, 4e

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Chapter 11

A

B

FIG. 11.52.  DCIS, low grade. A: Solid DCIS. B: Micropapillary architecture.

to 2.216 for comedocarcinoma, but the differences were not statistically significant. Bose et al. 101 analyzed periductal angiogenesis using factor VIII and CD34 immunostains in comedo and non- comedo types of DCIS. Small capillaries were usually pres- ent in the connective tissue, but they were sparse in the region of the basement membrane around normal ducts. New vessel formation associated with DCIS was limited to the region of the basement membrane in ducts with DCIS (Fig. 11.54). Evidence of angiogenesis was found in 80% of DCIS consisting of a ring of neovascularity completely or partially encircling the affected duct. A complete ring was found more often around comedo DCIS, whereas non- comedo lesions tended to have a partial ring or no periduc- tal neovascularity (Figs. 11.28 and 11.54). Using a different method of quantitation, Guidi and Schnitt 166 confirmed that maximal periductal neovascularity was associated

with comedocarcinoma, the expression of HER2, and with a high PI. Engels et al. 167 compared DCIS with increased stromal vascularity in between affected ducts, which they termed “pattern I” and lesions in which neovascularity formed a dense rim around the basement membrane (“pattern II”). Patterns I and II were present alone in 11% and 16%, re- spectively, of 75 cases. Increased vascularity with either pat- tern alone or in combination was associated with high-grade forms of DCIS. The observed pattern of angiogenesis may be related in part to the fate of myoepithelial cell layer in ducts that develop DCIS. Myoepithelial cells are more likely to per- sist in low-grade DCIS, and they are usually markedly at- tenuated or absent in high-grade or comedo DCIS. It has been suggested that myoepithelial cells may exert a tumor suppressor influence on the development or progression of DCIS. 104,168,169 Several lines of evidence appear to sup- port this hypothesis. In vitro and in situ tissue studies have demonstrated that myoepithelial cells express high amounts of proteinase inhibitors, including maspin, pro- tease nexin II, and α 1 -antitrypsin, and that these inhibi- tory proteins are concentrated in the stroma surrounding ducts. 170,171 The effect of these inhibitors of matrix metal- loproteinases is to decrease tumor invasiveness and to re- duce angiogenesis. 105,170 Angiogenesis associated with DCIS may also be modu- lated by the ability of the neoplastic cells to express angio- genic proteins such as the vascular endothelial growth factor (VEGF). High-grade DCIS and a significantly higher mi- crovessel count have been associated with stronger VEGF mRNA expression detected by in situ hybridization. 172 Vasohibin-1 is a negative feedback regulator of angiogen- esis. The status of neovascularization can be determined by the expression of vasohibin-1 mRNA that was more highly expressed in higher grade of DCIS in one study 173 ; however, data regarding the degree of angiogenesis in various grades of DCIS are conflicting. 174

FIG. 11.53.  DCIS, low and high nuclear grade in a single duct.