In
papillary thyroid cancer (PTC), age appears to be the most important single prognostic factor. Another characteristic feature is the lack of association between survival and
lymph node metastases. Earlier, we found that expression of
cyclooxygenase-2 (COX-2) is higher in older PTC patients, in agreement with the finding that older patients have a worse prognosis. Recent findings suggest that COX-2 can up-regulate
vascular endothelial growth factor-C (
VEGF-C) expression. Here, we investigated whether expression of
VEGF-C differs between young and older PTC patients and whether expression of
VEGF-C and COX-2 are correlated. Our retrospective study comprised 106 PTC patients selected by age: those under 35 or over 55 at diagnosis.
Paraffin-embedded tissue samples were analysed by immunohistochemistry for
VEGF-C protein expression. Furthermore, we investigated by quantitative RT-PCR and
enzyme immunoassay the relationship between
VEGF-C and COX-2 expression in
papillary thyroid cancer cells (NPA cells).
VEGF-C expression was significantly increased with age. In the tumours from older lymph node-positive (N1) patients,
VEGF-C expression was significantly higher than in the tumours from young N1 patients. Moreover, all patients who died of
cancer or who developed distant
metastases were old, and most tumours from these patients (4 of 5) expressed
VEGF-C and had had nodal
metastases at the time of primary operation. Immunohistochemically, expression of COX-2 and
VEGF-C correlated strongly. In cell culture, this correlation was not so clear, because the COX-2 selective inhibitor,
NS-398, did not reduce
VEGF-C expression. However, as both COX-2 and
VEGF-C were induced by the tumour promoter
phorbol 12-myristate 13-acetate (PMA), the same factors may control them both.