Immunohistochemical and in situ hybridization analyses of midkine expression in thyroid papillary carcinoma

Midkine (MK) is a novel heparin-binding growth factor whose gene has been i dentified in embryonal carcinoma cells in early stages of retinoic acid-ind uced differentiation. We immunohistochemically examined 90 thyroid papillar y carcinomas (85 invasive type and five encapsulated type), using a rat IgG 2a monoclonal antibody against the carboxyl terminal region of human MK in archival paraffin sections. The thyroid tumors exhibited an intense reactio n in the cytoplasm. Most of the papillary carcinomas (77/90), had tumor cel ls that expressed MK. These were classified into the following two types: i nvasive type (76/85) and encapsulated type (1/5). Notably, the intensity of MK was stronger at the invading border area of the tumors than in the cent er. In tissues adjacent to the cancer tissues, normal follicular epithelial cells expressed MK very faintly or not at all. The in situ hybridization a nalysis revealed that the signals of MK transcripts were found in the cytop lasm of the cancer cells. In the noncancerous follicular epithelial cells a djacent to neoplasm the signals of MK transcripts were detected very weakly or not at all. The distribution and localization of the MK-transcript sign als determined by in situ hybridization analysis were similar to those obta ined by immunohistochemical analysis. We conclude that thyroid papillary ca rcinoma strongly expresses MK protein and messenger RNA, and that this over expression may relate to the development and invasion of these carcinomas.