PDGFRα/β expression correlates with the metastatic behavior of human colorectal cancer: A possible rationale for a molecular targeting strategy

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 a and β (PDGFRa/β) in human colorectal cancer. The co-expression pattern of PDGFRa/β 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 PDGFRa and PDGFRβ. The majority of human colorectal cancer specimens revealed a PDGFRa (83%) or PDGFRβ (60%) expression. While PDGFRa showed a predominantly cytoplasmic staining in tumor cells as well as in stromal pericytes, PDGFRfi was restricted to stromal pericytes only. Furthermore, PDGFRa 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). PDGFRβ expression only revealed a trend towards lymphatic dissemination (P=0.099). Co-expression of PDGFRa/β occurred in 57% of the colorectal cancer samples, whereas another 29% of the samples depicted mono-expression of PDGFRa or PDGFRfi. Notably, PDGFRa/β 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 PDGFRα/β expression significantly correlates with lymphatic dissemination and therefore encourages application of PDGFRa/B RTK-inhibitors within a combination therapy.