title: PDGFRalpha/beta expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategy.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Johannes Gutenberg University of Mainz, 55101 Mainz, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wehler
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frerichs
authors.forename: Claudine
authors.initials: C
authors.lastname: Graf
authors.forename: Daniel
authors.initials: D
authors.lastname: Drescher
authors.forename: Katrin
authors.initials: K
authors.lastname: Schimanski
authors.forename: Stefan
authors.initials: S
authors.lastname: Biesterfeld
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
authors.forename: Stephan
authors.initials: S
authors.lastname: Kanzler
authors.forename: Theodor
authors.initials: T
authors.lastname: Junginger
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.forename: Carl C
authors.initials: CC
authors.lastname: Schimanski
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta