SMAD4 and neoplasm: To clarify this apparent discordance between mouse and man, and to establish whether SMAD4 behaves as a classical tumor suppressor gene or if, analogous to the Smad4 mouse models, haploinsufficiency underlies early stages of tumor formation in man, we performed SMAD4 immunohistochemistry (IHC) analysis of juvenile polyps from six unrelated JPS patients with known SMAD4 germline mutations (Table 1).