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The Significance Of Expression Of Vascular Endothelial Cell Growth Factor Families And Their Receptors In Breast Carcinoma And Being A Target For Antiangiogenesis Therapy

Posted on:2004-11-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:X LiuFull Text:PDF
GTID:1104360092495549Subject:Department of General Surgery
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1. The mRNA Expression of Vascular Endothelial Cell Growth Factor Families and Their Receptors in Breast Cancer Tissues and Its Clinical SignificanceObjective To study the mRNA expression of vascularendotheliai cell growth factor families (VEGFs) and their receptors in breast cancer and the clinical significance.Methods The mRNA expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D and their receptors, FLT-1, FLK-1, FLT-4, neuropilin (NP)-1, NP-2 and soluble FLT-1 (sFLT-1), were detected by reverse transcription- polymerase chain reaction (RT-PCR) in the specimens from 47 patients with breast cancer and 11 patients with benign breast disease who received operation between November 2000 and August 2001. The correlation with breast cancer clinicopathological factors was also analyzed. Results VEGF-A 121, 165 mRNA were all detected inmalignant and benign breast tissues, with a higher level, 0.420 ?0.133 and 0.291 ?0.094 respectively, in breast cancer tissues than in benign breast tissues, 0.196 ?.067 (P = 0.000) and 0.206 ?0.058 (P = 0.001) respectively. The expression of VEGF-A 121 mRNA were stronger than VEGF-A 165 mRNA (P = 0.000) in breast cancer tissues, whereas there was no significant difference in benign breast tissues (P = 0.666). VEGF-B 167 mRNA was detected in all the malignant and benign breast tissues, while VEGF-B 186 mRNA was detected in 37 of 47 (78.7%) breast cancer tissues and in 6 of 11 (54.5%) benign breast tissues. The expression of VEGF-B167 mRNA seemed to be higher in breast cancer tissues, 0.222 ?0.078, than in benign breast tissues, 0.176 ?.062, but there was no significant difference (P = 0.077). The expression of VEGF-B 186 mRNA was higher in breast cancer tissues, 0.167 (0.080-0.219), than in benign breast tissues, 0.071 (0.000-0.156) (P = 0.010). The expression of VEGF-C mRNA was detected in 28 of 47 (59.6%) breast cancer tissues, higher than in benign breast tissues, 2 of 11 (18.2%) (P = 0.013). The expression of VEGF-D mRNA was higher in breast cancer tissues, 24 of 47 (51.1%), than in benign breast tissues, 1 of 11 (9.1%) (P = 0.016). The expression of FLT-1 mRNA was detected in 18 of 47 (38.3%) breast cancer tissues but none in benign breast tissues (P = 0.012). The expression of FLK-1 mRNA was detected in 12 of 47 (25.5%) breast cancer tissues but none in benign breast tissues (P = 0.097). The expression of FLT-4 mRNA was detected in 24 of 47 (51.1%) breast cancer tissues but none in benign breast tissues (P = 0.002). The expression of NP-1 mRNA was detected in 23 of 47 (48.9%) breast cancer tissues but none in benign breast tissues (P = 0.002 ). NP-2 mRNA has two isoform, aO and a17/a22, which were detected overall in 27 of 47 (57.4%) but none in benign breast tissues (P = 0.001). The expression of sFLT-1 mRNA was detected in 35 of 47 (74.5%) breast cancer tissues and in 8 of 11 (72.7%) benign breast tissues, and the median level was 0.348 (0.000-0.457) and 0.366 (0.000-0.353), respectively, with no significant difference (P = 0.401). There were no correlation between the expression of VEGF-A 121, 165, VEGF-B 167, 186, FLT-1, FLK-1, NP-1, NP-2 mRNA in breast cancer tissues and patients' age, tumor size, lymph node metastasis, tumor stage, estrogen or progesterone receptor status. The expression of VEGF-C (P = 0.037), VEGF-D (P = 0.012) and FLT-4 mRNA (P = 0.012) in breast cancer tissues correlated with lymph node metastasis, but did not correlate with other clinicopathological factors. Moreover, the expression of FLT-4 mRNA in breast cancer tissues correlated with VEGF-C (P = 0.028) and VEGF-D mRNA (P= 0.029).Conclusion The mRNA expression of VEGF-A, VEGF-B,VEGF-C, VEGF-D and their receptors, FLT-1, FLK-1, FLT-4, NP-1and NP-2, increased variantly in breast cancer tissues, whichsuggested important roles in breast cancer angiogenesis andlymphangiogenesis.2. The Protein Expression of Vascular Endothelial Cell Growth Factor Families and Their Recept...
Keywords/Search Tags:Breast neoplasms Vascular endothelial cell, growth factor Vascular endothelial cell growth factor receptor, Angiogenesis Lymphangiogenesis Microvascular density, Microlymphatic density, Proliferating cell nuclear antigen
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