Anaplastic lymphoma kinase (ALK) gene aberrations are found in several
tumor types including
anaplastic large cell lymphoma (ALCL) and
non-small cell lung cancer (NSCLC).
Crizotinib, an inhibitor of ALK-fusion
proteins, has shown clinical activity, but resistance mechanisms limit long-lasting disease control. It has been shown that ALK-NPM fusion upregulates
platelet-derived growth factor receptor beta (
PDGFRB) via JUN and
transcription factor Jun B (JUNB) in ALCL.
PDGFRB inhibition has been identified as
therapy option for ALK-positive ALCL. Here, we investigated the ALK/JUN/JUNB/
transcription factor Jun C (JUNC)/PDGFR axis in metastatic NSCLC with regard to ALK aberrations. We performed immunohistochemical analysis of
platelet-derived growth factor receptor alpha (PDGFRA),
PDGFRB, JUNB and JUNC expression in
formalin-fixed,
paraffin-embedded specimens of 15 NSCLC
brain metastases (5 ALK translocations, 3 of them involving EML4, 5 ALK amplifications, 5 without ALK aberrations). We did not find a statistically significant difference in expression of PDGFRA,
PDGFRB, JUNB or JUNC in
tumor samples with normal ALK status, ALK amplification or ALK translocations (Kruskal-Wallis test p > 0.05). Interestingly,
PDGFRB was not expressed in
tumor cells (but in vascular and stromal cells) in any of our cases. Our data argue against
PDGFRB activation in association with ALK gene aberrations in metastatic NSCLC and thus seem to imply differential pathobiological roles of ALK alterations in
lung cancer and
lymphoma, possibly depending on different fusion partner genes. These results may be relevant for targeted
therapies, as they indicate that inhibition of
PDGFRB in ALK translocated NSCLC seems to be no therapeutic opportunity.