Downregulation of p27(KIP1) and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories

The cyclin-dependent kinase inhibitor p27(KIP1) has been proposed as a valu able prognostic indicator for a variety of human neoplasms. Immunohistochem ical reactivity for p27(KIP1) and the proliferation marker Ki67/Mib1 were i nvestigated in 90 thyroid carcinomas of follicular cell origin. The neoplas ms were divided into three prognostic groups on the basis of their morpholo gic features: group I, well-differentiated papillary or follicular carcinom as with favorable pathologic features (43 papillary carcinomas and 4 minima lly invasive follicular carcinomas); group 2, papillary or follicular carci nomas with unfavorable pathologic features (21 poorly differentiated carcin omas and 2 papillary carcinomas, tall cell variant); and group 3, undiffere ntiated, or anaplastic, carcinomas, p27(KIP1) expression (p = 0.007) and Ki 67/Mib1 labeling index (p = 0.07) showed a strong correlation with the subd ivision of the thyroid carcinomas in the three prognostic groups with a sig nificant linear trend for tumors with low p27(KIP1) (P = 0.002) and high Ki 67/Mib1 labeling index (p = 0.005) to segregate into the unfavorable catego ries (groups 3, and 3). Low p27(KIP1) expression, but not cellular prolifer ation, was related to adverse prognostic factors, such as large tumor size (p = 0.03) and extrathyroidal extension (p = 0.01), but the correlation was not independent of the subdivision in the three groups. Low p27(KIP1) expr ession (p = 0.03) and high proliferative rate (p = 0.02) were associated wi th poor survival, reflecting the close association between patient morbidit y and mortality rates and tumor differentiation. No significant association could be seen between p27(KIP1) or cellular proliferation and clinicopatho logic parameters (e.g., age, sex, tumor size, extrathyroidal extension, vas cular invasion, lymph node metastases, distant metastases, tumor stage, and survival rate) within any of the groups, or the histologic diagnosis of pa pillary versus follicular carcinoma irrespective of their degree of differe ntiation, Modulation of p27(KIP1) and cellular proliferation patterns in th yroid carcinoma correlate with tumor differentiation and support the morpho logic classification of thyroid carcinoma into prognostically relevant cate gories.