Cancer Stem Cells Markers in Human Thyroid Tumorigenesis: Role of p63 in Anaplastic Thyroid Carcinoma
AR Laury, C Nucera, V Nose. Brigham & Women's Hospital, Boston; Beth Israel Deaconess Medical Center, Boston; Harvard Medical School, Boston
Background: The term stem cell describes cells capable of both prolonged self-renewal and differentiation into specialized cells. Evidence suggests that a small subpopulation of tumor cells has stem cell-like properties, and tumors may initiate and progress from these cells. A stem cell role for the cells of solid cell nests and the theory of a p63-positive thyroid stem-like cell has been proposed in differentiated thyroid tumors. Association with a stem cell phenotype has also been reported for CD44, CD133, and OCT3/4. The aim of this study is to evaluate a panel of potential cancer stem cell markers in order to identify cell subpopulations in normal, benign, differentiated tumors, and anaplastic thyroid carcinoma.
Design: 15 cases of anaplastic thyroid carcinoma (ATC) and 15 cases each of papillary thyroid carcinoma (PTC), follicular carcinoma (FC), and follicular adenoma (FA) were retrieved from the hospital files and consult archives. Immunohistochemical staining for p63, CD44, CD133, and OCT3/4 was performed on formalin fixed paraffin embedded tissue. The results were scored as weak, moderate, or strong and semiquantitatively as 1+ (<5%), 2+ (5-10%), 3+ (10-50%), and 4+ (>50%). Only nuclear staining was scored as positive for OCT3/4 and p63; cytoplasmic or membranous staining was scored as positive for CD44 and CD133.
Results: Nuclear positivity for p63 was diffusely present in 7 (47%) ATC cases, focally in 3 PTCs (in squamous metaplasia), and absent in FTC and FA. Nuclear positivity for OCT3/4 was present in 3 (27%) ATC, 6 (40%) PTC, 2 (14%) FC, and 1 (7%) FA. Diffuse membranous staining for CD44 was seen in all 15 ATC; cytoplasmic staining was also observed in 6 cases. All cases of FA, FC, PTC, benign, and normal follicular cells stained for CD44. Diffuse cytoplasmic staining for CD133 was seen in all 15 ATC, and was subjectively increased as compared to adjacent normal thyroid, FA, FC, and PTC.
Conclusions: Our findings support the theory of the existence of a p63-positive thyroid stem-like cell, and suggest that p63 may play an important role in tumor progression and anaplastic thyroid carcinoma. OCT3/4 may also play a role in these tumors. Stem cell markers CD44 and CD133 did not distinguish the cells. Further functional studies should be performed to better characterize and identify thyroid cancer stem cells. Finally, thyroid cancer stem cell identification will provide a specific target for therapy of advanced thyroid carcinomas.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 34, Tuesday Afternoon