MHC class II expression in pediatric ACT

Purpose: Histological markers that differentiate benign and malignant pediatric adrenocortical tumors (ACTs) are lacking. Previous studies have implicated an association of major histocompatibility complex (MHC) class II expression with ACT prognosis. Here we determined the expression of MHC class II as well as the cell of origin of these immunological markers in pediatric ACT. The impact of MHC class II gene expression on outcome was determined in a cohort of uniformly-treated children with adrenocortical carcinomas. Experimental Design: We analyzed the expression of MHC class II and a selected cluster of differentiation genes in 63 pediatric ACTs by Affymetrix Human U133 Plus 2.0 or HT HG-U133+PM gene chip analyses. Cells expressing MHC class II were identified by morphologic and immunohistochemical assays. Results: MHC class II expression was significantly greater in adrenocortical adenomas than in carcinomas (P = 4.8 x 10-6) and was associated with a higher progression-free survival (PFS) estimate (P = 0.003). Specifically, HLA-DPA1 expression was most significantly associated with PFS after adjustment for tumor weight and stage. HLA-DPA1 was predominantly expressed by hematopoietic infiltrating cells and undetectable in tumor cells in 23 of 26 cases (88%). Conclusions: MHC class II expression, which is produced by tumor- infiltrating immune cells, is an indicator of disease aggressiveness in pediatric ACT. Our results suggest that immune responses modulate adrenocortical tumorigenesis, and may allow the refinement of risk stratification and treatment for this disease.

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