Muehling Bernd M, Toelkes Sara, Schelzig Hubert, Barth Thomas F E, Sunder-Plassmann Ludger
Department of Thoracic and Vascular Surgery, University of Ulm, Steinhövelstrasse 9, 89075 Ulm, Germany.
Interact Cardiovasc Thorac Surg. 2010 Feb;10(2):228-31. doi: 10.1510/icvts.2009.218263. Epub 2009 Nov 30.
Tyrosine kinase inhibitors against the receptors of vascular endothelial growth factor (VEGFR), epidermal growth factor (EGFR) and the platelet derived growth factor (PDGFR) are increasingly used in the treatment of progressive cancers. However, the expression of these receptors especially in lung metastases has not been examined. Tissue specimen from 35 lung metastases of 33 patients with renal cell carcinoma (n=8), sarcoma (n=10), colorectal carcinoma (n=6), otolaryngologic carcinoma (OLC, n=4), testicular and endometrial cancer (n=1 each), malignant melanoma (n=1), adrenal cancer (n=2), malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor (n=1 each) have been immunohistochemically tested for the expression of PDGFR alpha/beta, VEGFR and EGFR. None of the patients had been pretreated with angiogenic inhibitors prior to metastasectomy. PDGFRalpha was expressed in all metastases; 31% stained negative for PDGFRbeta, 86% negative for VEGFR and 45% negative for EGFR. Primary tumors revealed positive staining for PDGFRalpha in 88%, for PDGFRbeta in 59%, for VEGFR in 0% and for EGFR in 18%. Our investigation of a pilot character represents a 'biomarker-based' analysis of pulmonary metastases of different primary tumors; we conclude that an immediate 'tumor profiling' at initial diagnosis should be considered in order to guide tumor therapy individually.
针对血管内皮生长因子(VEGFR)、表皮生长因子(EGFR)和血小板衍生生长因子(PDGFR)受体的酪氨酸激酶抑制剂越来越多地用于治疗进展期癌症。然而,这些受体的表达情况,尤其是在肺转移灶中的表达情况尚未得到研究。对33例患者的35个肺转移灶组织标本进行了免疫组化检测,这些患者分别患有肾细胞癌(8例)、肉瘤(10例)、结直肠癌(6例)、耳鼻喉科癌(OLC,4例)、睾丸癌和子宫内膜癌(各1例)、恶性黑色素瘤(1例)、肾上腺癌(2例)、恶性纤维组织细胞瘤和恶性周围神经鞘瘤(各1例),检测其PDGFRα/β、VEGFR和EGFR的表达。在进行转移灶切除术前,所有患者均未接受过血管生成抑制剂治疗。所有转移灶均表达PDGFRα;31%的转移灶PDGFRβ染色阴性,86%的转移灶VEGFR染色阴性,45%的转移灶EGFR染色阴性。原发肿瘤中,88%的PDGFRα染色阳性,59%的PDGFRβ染色阳性,0%的VEGFR染色阳性,18%的EGFR染色阳性。我们这项初步研究是对不同原发肿瘤肺转移灶进行的一项“基于生物标志物”的分析;我们得出结论,为了个体化指导肿瘤治疗,应考虑在初始诊断时立即进行“肿瘤分型”。