Cyclin D1 Expression in Benign and Malignant Differentiated Tumors of the Thyroid Gland.
Timothy P Seybt (1), Preetha Ramalingam, Jie Huang (2), Stephen W Looney (2), Michelle D Reid. Georgia Health Sciences University, Augusta; Emory University Hospital, Atlanta, GA
Background: The gold standard for diagnosis of thyroid tumors is histology, which is often challenging and subjective. Morphologic overlap between benign and malignant tumors also occurs frequently. We examined cyclin D1 expression in benign and malignant differentiated thyroid tumors to determine its diagnostic utility and correlation with tumor type and node (LN) status.
Design: Twenty-nine (29) follicular adenomas (FA), 23 follicular carcinomas (FCA) and 43 papillary thyroid carcinomas (PTC) (including 22 with and 21 without nodal metastases), were stained with cyclin D1. PTCs included 27 classical (PTCC) and 16 follicular variants (PTCFV). Staining intensity was negative (0), weak (1+), moderate (2+) or strong (3+). Stain distribution was negative (0%); 1+ (<25%); 2+ (25-75%) or 3+ (>75%) of tumor cells. Cochran-Mantel-Haenszel method tested for significant associations of cyclin D1 staining, distribution and intensity with tumor type (FA, FCA, PTC), tumor type after subtyping PTCs (FA, FCA, PTCC and PTCFV), and PTC LN status.
Results: 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). Stain distribution was greater in PTC than FA (p=0.032). More PTCs were (+) than FCAs (88% vs 61% respectively; p=0.013). FA did not differ significantly from FCA in staining or intensity. There were fewer cyclin D1 (+) 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 cyclin D1 staining (61% vs 89% respectively; p=0.044) and intensity (p=0.024). FA had significantly less intense staining than PTCC (p=0.004). No significant associations were found between PTC LN status and any cyclin D1 characteristic.
Conclusions: Frequency and intensity of cyclin D1 expression was increased in differentiated malignant tumors relative to benign ones, and was progressively amplified from FAs to carcinomas (PTC and FCA). Distribution and intensity was significantly higher in (all) PTCs than FA and FCA, especially FA. The heterogeneity in distribution and intensity of staining in all thyroid tumor types disqualifies cylcin D1 as a primary diagnostic marker. However, it may be helpful in distinguishing FA from PTC, especially PTCFV. Cyclin D1 expression by benign and malignant thyroid tumors suggests a possible role in tumor development and progression, which should be investigated further.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 38, Tuesday Afternoon