Wehler Thomas C, Frerichs Kirsten, Graf Claudine, Drescher Daniel, Schimanski Katrin, Biesterfeld Stefan, Berger Martin R, Kanzler Stephan, Junginger Theodor, Galle Peter R, Moehler Markus, Gockel Ines, Schimanski Carl C
Third Department of Internal Medicine, Johannes Gutenberg University of Mainz, 55101 Mainz, Germany.
Oncol Rep. 2008 Mar;19(3):697-704.
As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRalpha and PDGFRbeta. The majority of human colorectal cancer specimens revealed a PDGFRalpha (83%) or PDGFRbeta (60%) expression. While PDGFRalpha showed a predominantly cytoplasmic staining in tumor cells as well as in stromal pericytes, PDGFRbeta was restricted to stromal pericytes only. Furthermore, PDGFRalpha expression significantly correlated with lymph node metastasis (P=0.0082) and advanced UICC stages III/IV (P=0.018) in older patients (P=0.043). PDGFRbeta expression only revealed a trend towards lymphatic dissemination (P=0.099). Co-expression of PDGFRalpha/beta occurred in 57% of the colorectal cancer samples, whereas another 29% of the samples depicted mono-expression of PDGFRalpha or PDGFRbeta. Notably, PDGFRalpha/beta expression significantly correlated with lymphatic metastasis (P=0.007) and advanced UICC stages III/IV (P=0.017) in older patients (P=0.03). In summary, our results revealed that PDGFRalpha/beta expression significantly correlates with lymphatic dissemination and therefore encourages application of PDGFRalpha/beta RTK-inhibitors within a combination therapy.
随着新型多靶点酪氨酸激酶抑制剂在各种恶性肿瘤治疗中的不断涌现，我们的目标是确定人结直肠癌中受体酪氨酸激酶血小板衍生生长因子受体α和β（PDGFRα/β）的共表达模式。通过逆转录聚合酶链反应（RT-PCR）分析了99例经组织学确诊的人结直肠癌和5种结直肠癌细胞系中PDGFRα/β的共表达模式。此外，应用免疫组织化学（IHC）染色来确认表达情况并分析受体酪氨酸激酶（RTK）的定位。所分析的结直肠癌细胞系显示出PDGFRα和PDGFRβ不同的表达强度。大多数人结直肠癌标本显示出PDGFRα（83%）或PDGFRβ（60%）表达。虽然PDGFRα在肿瘤细胞以及基质周细胞中主要呈细胞质染色，但PDGFRβ仅局限于基质周细胞。此外，在老年患者（P=0.043）中，PDGFRα表达与淋巴结转移（P=0.0082）及国际抗癌联盟（UICC）III/IV期晚期（P=0.018）显著相关。PDGFRβ表达仅显示出淋巴扩散的趋势（P=0.099）。57%的结直肠癌样本中出现PDGFRα/β共表达，而另外29%的样本呈现PDGFRα或PDGFRβ的单表达。值得注意的是，在老年患者（P=0.03）中，PDGFRα/β表达与淋巴转移（P=0.007）及UICC III/IV期晚期（P=0.017）显著相关。总之，我们的结果表明，PDGFRα/β表达与淋巴扩散显著相关，因此鼓励在联合治疗中应用PDGFRα/β RTK抑制剂。
