Irrespective of the mechanism whereby p16 reduced lymphangiogenesis our results strongly support the proposed sequence of p16 induction, reduction of lymphangiogenesis, and prevention of lymphatic metastasis in pancreatic cancer, as (i) p16 significantly inhibited lymph node metastasis, and (ii) mice with lymph node infiltration had significantly higher LVDs in their primary tumours. This evidence concerns the gene CDKN2A and familial pancreatic carcinoma.