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悪性胸膜中皮腫における腫瘍組織内リンパ管密度および血管密度とVEGF関連血管新生因子との相関性 : 太田安彦¹、渡辺洋宇¹、佐々木琢磨²、Harvey I. Pass^3,(¹金沢大・医・¹外、²金沢大・医・がん研・化療、³Karmanos Cancer Inst., Detroit, Michigan, USA)

VEGF, VEGF Type C, and their receptors play an important role in angiogenesis and lymphangiogenesis in malignant mesothelioma tumors: Yasuhiko OHTA¹, Yoh WATANABE¹, Takuma SASAKI², Harvey I. PASS^3, (1First Dept. of Surgery, Kanazawa Univ., ²Dept. of Experimental Therapeutics,Cancer Research Inst., Kanazawa Univ., ^3,Dept. of Surgical Oncology, Karmanos Cancer Inst., Detroit, USA)

We assessed mRNA expression of VEGF, VEGF-C, and their receptors together with microvessel density (VD) and microlymphatic vessel density (LVD) in malignant pleural mesothelioma (MPM). We used 4 human MPM cell lines, 54 MPM tumors, and 5 normal pleurae. Expression levels were assessed by semiquantitative RT-PCR analysis. Microvessels were highlited by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzymehis-tochemistry for 5ユ-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C, and VEGFRs were high in all MPM cell lines. The percentages of tumors with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for flt-1, 42.6% (23/54) for KDR, and 59.3% (32/54) for flt-4. Significant positive co-rrelations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumors. The association between LVD and VEGF-C expression was especially strong (p<0.0001, r=0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGF/VEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumor. malignant pleural mesothelioma (MPM). We used 4 human MPM cell lines, 54 MPM tumors, and 5 normal pleurae. Expression levels were assessed by semiquantitative RT-PCR analysis. Microvessels were highlited by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzymehis-tochemistry for 5ユ-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C, and VEGFRs were high in all MPM cell lines. The percentages of tumors with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for flt-1, 42.6% (23/54) for KDR, and 59.3% (32/54) for flt-4. Significant positive co-rrelations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumors. The association between LVD and VEGF-C expression was especially strong (p<0.0001, r=0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGF/VEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumor.