ANGIOGENESIS AS A DIAGNOSTIC FACTOR IN PRIMARY BREAST-CANCER - MICROVESSEL QUANTITATION BY STEREOLOGICAL METHODS AND CORRELATION WITH COLORDOPPLER SONOGRAPHY

Background: In contrast to benign lesions without signs of inflammatio n, malignant tumors have a capacity for angiogenesis. Therefore it was of interest to evaluate with color Doppler ultrasound if breast carci nomas showed higher vascularization than benign lesions. To enable a c orrelation with the pathoanatomic situation of vascularization, stereo logical methods were used to quantify microvessel volume, surface and length as indicators for angiogenesis. Patients and Methods: Two hundr ed and five patients with a palpable and/or mammographically seen brea st tumor were investigated before they underwent surgery with color Do ppler ultrasound for the detection of blood flow in the tumor or in an area around the tumor within a distance of 2 cm. In 101 cases microve ssels of the tumor were identified by immunohistochemistry using the m onoclonal mouse antibody (JC70) that detects the vascular endothelium- associated antigen CD31 and quantified by stereological methods. The q uantified vessel volume, surface, and length were compared to color fl ow results and other prognostic factors in breast cancer. Results: The detection of blood flow by color Doppler sonography in the tumor and in the peritumoral region was significantly higher in malignant than i n benign breast lesions (p=0.003). By stereological quantitation of mi crovessels it could be shown that breast carcinoma had a significantly higher volume, surface and length of vessels than fibroadenoma (p<0.0 0001 and p<0.0001). In the group of breast cancers a significant corre lation was found between high length of microvessels per mm(3) tumor a nd tumor size (p=004 - Jonckheere test), a negative estrogen receptor (p<0.007) and a negative progesterone receptor (p=0.005). No correlati on was found between microvessel length and nodal status, tumor grade, ploidy status, and S-phase fraction. Conclusions: Microvessel count i n breast tumors, using the JC70 antibody to CD31, and stereology for q uantitation in a three-dimensional fashion, is an effective method to look for the extent of angiogenesis and to correlate Doppler flow resu lts with pathoanatomic vascular data. With color Doppler sonography an effective clinical method is available for distinguishing between ben ign and malignant lesions.