Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays.
Quantitative expression of VEGF, VEGF-R1, VEGF-R2, and VEGF-R3 in melanoma tissue microarrays.
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DOI：
10.1016/j.humpath.2009.08.016
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发表时间：
2010-03
期刊：
影响因子：
3.3
通讯作者：
Kluger, Harriet M.
中科院分区：
文献类型：
--
作者：
Mehnert, Janice M.;McCarthy, Mary M.;Jitaveanu, Lucia;Flaherty, Keith T.;Aziz, Saadia;Camp, Robert L.;Rimm, David L.;Kluger, Harriet M.
血管生成是黑色素瘤进展和转移所必需的。分析良性和恶性组织中的血管生成分子可以识别用于预测抗血管生成剂敏感性的标记物。我们假设VEGF及其受体VEGF-R1、- R2和-R3的差异表达在黑色素瘤中高于痣，在晚期黑色素瘤中更高。使用自动定量分析（AQUA），我们定量VEGF，-R1，-R2和-R3表达的黑色素瘤组织微阵列组成的540痣和468黑色素瘤标本（198原发，270转移）。通过非配对t检验，VEGF、-R1、-R2和-R3在黑素瘤中的表达显著高于痣（p <0.0001）。VEGF-R2表达在转移性标本中较高（p <0.0001），但VEGF-R3表达在原发灶中较高（p < 0.0001）。VEGF与所有三种受体共表达时，由斯皮尔曼等级相关性进行评估。VEGF、-R1、-R2和-R3在黑色素瘤中的表达高于痣。转移瘤中VEGF-R2的表达高于原发瘤，这支持了转移性黑色素瘤中血管生成表型的选择是通过上调VEGF-R2来实现的观点。然而，VEGF-R3在原发性病变中的表达更高，可能涉及这种受体在淋巴肿瘤扩散的启动。在黑色素瘤中使用抗血管生成剂的临床试验应包括VEGF、-R1、-R2和-R3作为治疗反应生物标志物的相关测定，最好使用定量方法，如AQUA。这样的评估可以帮助评估这些分子作为黑色素瘤的治疗靶点，最终促进改善患者的治疗选择。
Angiogenesis is required for progression and metastasis of melanoma. Analysis of angiogenic molecules in benign and malignant tissues may allow identification of markers useful for prediction of sensitivity to antiangiogenic agents. We hypothesized that differential expression of VEGF and its receptors VEGF-R1, - R2, and -R3 would be higher in melanomas than nevi and higher in advanced melanoma. Using automated quantitative analysis (AQUA), we quantified VEGF, -R1, -R2 and -R3 expression in melanoma tissue microarrays composed of 540 nevi and 468 melanoma specimens (198 primaries, 270 metastases). VEGF, -R1, -R2 and -R3 expression was significantly higher in melanomas than nevi by unpaired t-tests (p <0.0001). VEGF-R2 expression was higher in metastatic specimens (p <0.0001), but VEGF-R3 expression was higher in primaries (p < 0.0001). VEGF was coexpressed with all three receptors when assessed by Spearman's rank correlation. VEGF, -R1, -R2 and -R3 expression is higher in melanomas than nevi. Higher expression of VEGF-R2 was found in metastases versus primaries, supporting the idea that selection for an angiogenic phenotype in metastatic melanoma is conferred via upregulation of VEGF-R2. However, higher expression of VEGF-R3 was seen on primary lesions, potentially implicating this receptor in initiation of lymphatic tumor spread. Clinical trials using antiangiogenic agents in melanoma should include correlative assays of VEGF, -R1, -R2 and -R3 as biomarkers of response to therapy, preferably using quantitative methods such as AQUA. Such assessments could assist with evaluation of these molecules as therapeutic targets in melanoma, ultimately facilitating improved selection of patients for treatment.
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影响因子：
45.3
作者：
Sabatino, Marianna;Kim-Schulze, Seunghee;Kaufman, Howard L.
通讯作者：
Kaufman, Howard L.
影响因子：
3.6
作者：
Graeven, U;Fiedler, W;Hossfeld, DK
通讯作者：
Hossfeld, DK
影响因子：
6.5
作者：
Graells, J;Vinyals, A;Fabra, A
通讯作者：
Fabra, A
索拉非尼靶标在用卡铂，紫杉醇和索拉非尼治疗的黑色素瘤患者中的表达。
DOI：
10.1158/1078-0432.ccr-08-2280
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jilaveanu L;Zito C;Lee SJ;Nathanson KL;Camp RL;Rimm DL;Flaherty KT;Kluger HM
通讯作者：
Kluger HM
影响因子：
4.5
作者：
Demirkesen, C;Büyükpinarbasili, N;Kaner, G
通讯作者：
Kaner, G