Cyclin D1 Expression in Benign and Differentiated Malignant Tumors of the Thyroid Gland: Diagnostic and Biologic Implications

Cyclin D1 expression was examined in benign and differentiated malignant thyroid tumors to determine diagnostic utility and correlation with tumor type, size, and nodal status; 29 follicular adenomas (FA), 23 follicular carcinomas (FCA) and 43 papillary thyroid carcinomas (PTC) (22 with and 21 without nodal metastases) were stained. PTCs included 27 classical (PTCC) and 16 follicular variants (PTCFV). A statistically significant association was found between tumor type and cyclin D1 staining, distribution, and intensity. There were fewer cyclin D1-positive FAs than PTCs (52% vs. 88% respectively; P < 0.001) and stain distribution was greater in PTC than FA (P = 0.032). More PTCs were positive than FCAs (88% vs. 61%, respectively; P = 0.013). All significant comparisons remained significant after adjusting for tumor size. FA did not differ from FCA in staining/intensity. There were fewer cyclin D1-positive FAs than PTCC (52% vs. 89%, respectively; P = 0.003) and PTCFV (52% vs. 88%, respectively; P = 0.023). FCA also differed significantly from PTCC in staining (61% vs. 89%, respectively; P = 0.044) and intensity (P = 0.024). In terms of cyclin D1 intensity, FA had significantly less intense staining than PTCC (P = 0.004). No significant associations were found between PTC nodal status and any cyclin D1 characteristic. In conclusion, cyclin D1 shows heterogeneity in distribution and intensity in benign and malignant thyroid tumors, which disqualifies it as a primary diagnostic marker in these tumors; however, it may be helpful in distinguishing FA from PTC, especially PTCFV. Its expression by thyroid tumors suggests a role in tumor development and may be an early event in thyroid neoplasia.