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Intense Expression of the B7-2 Antigen Presentation Coactivator Is an Unfavorable Prognostic Indicator for Differentiated Thyroid Carcinoma of Children and Adolescents

Department of Pediatrics, Uniformed Services University of the Health Sciences (R.S., K.B., A.P., S.D., R.T., P.A.P., C.F., C.A.D., G.L.F.), Bethesda, Maryland; Departments of Pediatrics (P.A.P., C.F., G.L.F.) and Clinical Investigation (C.A.D.), Walter Reed Army Medical Center, Washington, D.C.; and Department of Endocrinology, Memorial Sloan Kettering Cancer Center (R.M.T.), New York, New York

Abstract

Previous observations suggest that an immune response against thyroid carcinoma could be important for long-term survival. We recently found that infiltration of thyroid carcinoma by proliferating lymphocytes is associated with improved disease-free survival, but the factors that control lymphocytic infiltration and proliferation are largely unknown. We hypothesized that the antigen presentation coactivators (B7-1 and B7-2), which are important in other immune-mediated thyroid diseases, might be important in lymphocytic infiltration of thyroid carcinoma. To test this, we determined B7-1 and B7-2 expression by immunohistochemistry [absent (grade 0) to intense (grade 3)] in 27 papillary (PTC) and 8 follicular (FTC) thyroid carcinomas and 9 benign thyroid lesions. B7-1 and B7-2 were expressed by the majority of PTC and FTC (78% of PTC and 100% of FTC expressed B7-1; 88% of PTC and 88% of FTC expressed B7-2). B7-1 expression was more intense in PTC (1.4 ± 0.2; P = 0.01) and FTC (2.6 ± 0.2; P < 0.001) than in benign tumors (0.57 ± 0.30) or presumably normal adjacent thyroid (0.07 ± 0.07) and was more intense in carcinoma that contained lymphocytes (1.95 ± 0.21) than in carcinoma that did not (1.08 ± 0.26; P = 0.016). B7-2 expression was of similar intensity in benign and malignant tumors (PTC, 1.6 ± 0.2; FTC, 2.1 ± 0.4; benign, 1.86 ± 0.4), but was more intense than in presumably normal adjacent thyroid (0.64 ± 0.25; P 0.013). B7-2 expression also correlated with the number of tumor-associated lymphocytes per high power field (r = 0.38; P = 0.02). Recurrence developed exclusively from tumors that expressed B7-2, and intense B7-2 expression was associated with a reduced probability of remission (P = 0.04). In conclusion, these data support the hypothesis that the antigen presentation coactivators B7-1 and B7-2 may be important for lymphocytic infiltration and the immune response against thyroid carcinoma.

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