| Objectives: To examine the expression of tumor micro vessel density (MVD) and proangiogenic factors in breast invasive ductal carcinoma and intraductal proliferative lesion, analyze the relationship between MVD and proangiogenic factors and the role of tumor angiogenesis in breast carcinoma, and provide academic basis for anti-angiogenesis target therapy.Methods: Computer-assisted image analysis system and immunohistochemistry were used to detect the expression of MVD and VEGF, bFGF and PDGF in 152 routinely paraffin embedded specimens including 18 cases of normal breast (NB group), 20 cases of usual ductal hyperplasia (UDH group), 29 cases of atypical ductal hyperplasia (ADH group), 15 cases of ductal carcinoma in situ (DCIS group), and 70 cases of infiltrating ductal carcinoma (IDC group) . To evaluate MVD associated with the expression of proangiogenic factors in different hyperplastic phases of breast intraductal epithelial and compared with clinico-pathological parameters. Results: 1. MVD in breast invasive carcinoma and intraductal proliferative lesion1) MVD assessed by CD34 labellingMVD in NB, UDH, ADH, DCIS, and IDC group were 14.22 ± 2.89, 16.46 ±2.88, 24.97±4.42, 35.42 ± 3.52, and 42.32±2.95 respectively. There were significantly different among five groups in MVD (P<0.001 for all). there was no significant difference between NB and UDH group, but the significant differences among the other groups were found (P<0.001 for all) .2) MVD assessed by CD105 labellingMVDinNB, UDH, ADH, DCIS, and IDC group were 0, 11.11 + 1.13, 15.81 +2.95,25.82 + 4.10, and 30.26 + 3.59 respectively. There were significantly different among five groups in MVD (P<0.001 for all) , and the significant differences among every groups were found (/><0.001 for all) .2. MVD adjacent to the lesion and within the lesion in breast invasive carcinoma and intraductal proliferative lesion1) MVD adjacent to the lesion and within the lesion assessed by CD34 labellingMVD adjacent to the lesion and within the lesion in UDH, ADH, DCIS, and IDC group were 16.46 + 2.88 vs. 0, 24.97 + 4.42 vs. 0, 34.35 + 2.71 vs. 1.07 + 1.03, and 37.31+3.83 vs. 5.02+1.10 respectively, MVD adjacent to the lesion was significantly higher than those within the lesion in every growp (P<0.001 for all) . MVD adjacent to the lesion were significantly different among four groups (P<0.001) . Only there were microvessels within the lesion of DCIS growp and IDC growp , and MVD within the lesion of IDC growp were significantly higher than those of DCIS growp (P<0.001) .2) MVD adjacent to the lesion and within the lesion assessed by CD 105 labellingMVD adjacent to the lesion and within the lesion in UDH, ADH, DCIS, and IDC group were 11.11 + 1.13 vs. 0, 15.81+2.95 vs. 0, 24.35+4.07 vs. 1.47 + 1.88, and 27.13 + 3.81 vs. 3.13 + 2.29 respectively, MVD adjacent to the lesion was significantly higher than those within the lesion in every growp (i><0.001 for all) . MVD adjacent to the lesion were significantly different among four groups (P<0.001) . Only there were microvessels within the lesion of DCIS growp and IDC growp , and MVD within to the lesion of IDC growp were significantly higher than those of DCIS growp (P<0.001) .3. Positive expression of VEGF, bFGF, and PDGF in breast invasive carcinoma and intraductal proliferative lesionMean optical density (MOD) of positive expression of VEGF in NB, UDH,ADH, DCIS, and IDC group were 0.01 ±0.01, 0.02 ±0.01, 0.21+0.01, 0.32 ±0.02, and 0.51 ±0.04 respectively. Accordingly, MOD of bFGF in NB, UDH, ADH, DCIS, and IDC group were 0.03±0.01, 0.03±0.05, 0.19±0.03, 0.27 ±0.02, and 0.44±0.02 respectively. MOD of PDGF inNB, UDH, ADH, DCIS, and IDC group were 0.02±0.01, 0.03±0.04, 0.14±0.02, 0.25±0.01, and 0.34 ±0.01 respectively. There was no significant difference between NB and UDH group, but the significant differences among the other groups were found in VEGF, bFGF, and PDGF respectively (P<0.001 for all) .4. Correlation between MVD and proangiogenic factorsAlthough positive correlations between MVD by CD34 and CD 105 labelling and MOD of VEGF, bFGF, and PDGF were showed significantly respectively (/><0.01 for all) , the positive correlations were showed significantly only in DCIS and IDC group (P<0.01 for all) .5. Correlation between MVD and clinico-pathological parameters1) MVD by CD34 and CD 105 labelling in high-middle differentiated cases were significantly lower than those of low differentiated cases (P<0.05 for all) , and MVD were significanty positive correlated with tumor grade (P<0.05 for all) .2) MVD by CD34 and CD 105 labelling were significantly different among clinical stages (P<0.001 for all) , and MVD were significantly positive correlated with clinical stage (PO.01 for all).3) MVD by CD34 and CD105 labelling in axillary lymph node metastasis were significantly higher than those of without axillary lymph node metastasis (P<0.05 for all) , and MVD were significantly correlated with axillary lymph node metastasis (PO.01 for all), but no correlation were found between MVD and quantity of axillary lymph node metastasis.4) No correlation were found between MVD by CD34 and CD 105 labelling and tumor size.6. Correlation between proangiogenic factors and clinico-pathological parameters in IDC group1) MOD of VEGF, bFGF, and PDGF in high-middle differentiated cases were significantly lower than those of low differentiated cases (P<0.01 for all) , and MOD of every proangiogenic factor were significanty positive correlated with tumor grade (P<0.0l for all) .2) MOD of VEGF, bFGF, and PDGF in axillary lymph node metastasis were significantly higher than those of without axillary lymph node metastasis (P<0.05 for all) , and MOD of every proangiogenic factor were significantly correlated with axillary lymph node metastasis (P<0.05 for all).3) No correlation were found between MOD of every proangiogenic factor and tumor size and tumor stage.7. Correlation between MVD, proangiogenic factors and expression of PCNA in breast invasive carcinoma and intraductal proliferative lesion1) Positive correlations between MVD by CD 105 labelling and expression of PCNA was showed significantly (PO.01), and the expression of PCNA was the highest and MVD by CD 105 labelling was the highest in IDC growp, but no correlation was found between MVD by CD34 labelling and the expression of PCNA.2) MOD of VEGF, bFGF, and PDGF were significanty positive correlated with the expression of PCNA respectively (PO.01 for all), and the expression of PCNA was the highest and MOD of every proangiogenic factor were the highest in IDC growp.Conclusions:1. In this study, we provided a series of basic parameters for study change regularity of MVD and proangiogenic factors in UDH, ADH, DCIS, and IDC. Such studies haven't been searched in literatures.
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