Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma.

Abstract

The role of cell cycle inhibitors in tumorigenesis has been proven in various neoplasms; however, their roles in thymic tumors are still unclear. We examined the expression of cell cycle inhibitors such as those of the Cip/Kip family (p21, p27, and p57) and the INK-4/ARF family (p16 and p14) in thymoma and thymic carcinoma. Samples from 41 thymoma and 14 thymic carcinoma patients, and 34 normal thymic tissue samples were prepared for the study. Immunohistochemical analysis using antibodies to p21, p27, p57, p16, and p14 was carried out, and the positivity for these inhibitors in each group was estimated in terms of their subcellular location and percentage of cells showing positive staining. Nuclear p27 showed a stepwise decrease (p < 0.0001), and the cytoplasmic p27 showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. p16 in both the nucleus and cytoplasm showed a stepwise increase (p < 0.0001) in expression level with the increase in malignancy. However, as for p21, p57, and p14, there was almost no nuclear or cytoplasmic expression in each group. Our findings suggest that low nuclear and high cytoplasmic p27 expression levels, and high nuclear and cytoplasmic p16 expression levels may correlate with the increase in thymic malignancy.