Predicting the biologic behavior of ductal carcinoma in situ: An analysis of molecular markers

Background. Ductal carcinoma in situ (DCIS) of the breast encompasses a heterogeneous group of non-invasive cancers that now represents 19% of new breast cancer cases. Optimal treatment remains controversial. We undertook this study to characterize the relationship between angiogenic markers and the biologic behavior of various DCIS phenotypes. Methods. We performed histolopathologic review and immunohistochemistry for p53, vascular endothelial growth factor (VEGF), and factor VIII-related antigen on 103 specimens of pure DCIS. Results. VEGF expression was seen in 89 tumors (86%) and correlated with microvessel density (MVD). Among VEGF-negative tumors, mean MVD (number of microvessels per square millimeter) was 48±19, versus 117±7 for tumors expressing VEGF (P = .001). Strong p53 expression was observed in 28 tumors (27%) and was associated with comedo histology, high tumor grade, necrosis, high MVD, and ipsilateral tumor recurrence (all P≤.03). Among 8 patients with ipsilateral recurrence, 5 (63%) had tumors with strong p53 expression, whereas only 24% of patients without recurrence had tumors with strong p53 expression (P = .03). Although 7 of 8 patients with ipsilateral recurrence had tumors with VEGF and high MVD, neither parameter achieved statistical significance. Conclusions. These data suggest that molecular alterations may help predict the biologic aggressiveness of DCIS. Mutant p53 expression predisposes the patient toward ipsilateral recurrence, perhaps by promoting angiogenesis. Further investigation may identify clinically useful markers and novel treatment strategies.