p27(kip1) expression distinguishes papillary hyperplasia in Graves' disease from papillary thyroid carcinoma

In most cases, the histopathologic and cytologic distinction between Graves ' disease and papillary thyroid carcinoma is relatively easy, but on occasi on Graves' disease may simulate a thyroid papillary carcinoma For example, papillary fronds with fibrovascular cores may be present in both Graves' di sease and papillary carcinoma p27(kip1) (p27) is a cyclin-dependent kinase inhibitory protein that has been shown to be an independent prognostic fact or in a variety of human tumors. Our previous studies of p27 expression in hyperplastic and neoplastic endocrine lesions showed that the level of p27 was quite different in these two conditions. To determine if this distincti on could also be made between Graves' disease and papillary carcinoma, we a nalyzed expression of p27 and other cell cycle proteins in a series of case s of Graves' disease with papillary hyperplasia and a series of papillary t hyroid carcinomas. Formalin-fixed paraffin-embedded tissues from 61 randoml y selected patients with thyroid disease, including 29 cases of Graves' dis ease with papillary architectural features and 32 cases of papillary carcin oma, were analyzed for expression of p27, Ki-67, and DNA topoisomerase II a lpha (topo II alpha) by immunostaining. The distribution of immunoreactivit y was analyzed by quantifying the percentage of positive nuclei that was ex pressed as the labeling index (LT) plus or minus the standard error of the mean. The papillary hyperplasia of Graves' disease had a p27 LI of 68.2 +/- 3.1 (range, 24 to 88), whereas papillary carcinomas had a LI of 25.6 +/- 2 .5 (range, 12 to 70) (P <.0001). No significant differences in Ki-67 or top o II alpha expression were identified between papillary hyperplasia in Grav es' disease and papillary carcinoma These results indicate that p27 protein expression is significantly higher in papillary hyperplasia of Graves' dis ease compared to papillary carcinoma, which may be diagnostically useful in difficult cases.