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Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Each panel plots the rank of expression value in the cohort on the y-axis and the positive quantile transformation (PQT) value on the x-axis. Solid blue circles indicate adrenocortical carcinomas, open red circles indicate adrenocortical adenomas, and black X-marks indicate undetermined histology. In each plot, the gray rectangle highlights the large gap in the distribution that discriminates adenomas from carcinomas which was identified by the DGS criterion.

The Primary Antibodies Used for Immunohistochemistry Studies

Supplementary Fig 1. Discriminating gap size (DGS) criterion shows a gap in the distribution of the expression of MHC class II expression in the IPACTR cohort. Supplementary Fig 2. Immunohistochemical analysis of CD3, CD4, and CD8 expression.

Immunohistochemical analysis of CD3, CD4, and CD8 expression. Row: a) adenoma; b) stage I carcinoma; and c) stage III carcinoma. Note that cells with short processes are dimly positive for CD4, consistent with macrophages; cells with long process are also dimly positive for CD4, consistent with dendritic cells (Magnification, 100x; inset, 400x).

Probe-sets that Best Discriminated between Adenoma and Carcinoma in the IPACTR Cohort and Association with PFS in the COG Cohort

Clinical Data for Pediatric Adrenocortical Tumor patients

Association of HLA-DPA1 Expression with Clinical and Biological Characteristics of Uniformly Managed Pediatric Adrenocortical Carcinoma

Purpose: Histologic markers that differentiate benign and malignant pediatric adrenocortical tumors are lacking. Previous studies have implicated an association of MHC class II expression with adrenocortical tumor prognosis. Here, we determined the expression of MHC class II as well as the cell of origin of these immunologic markers in pediatric adrenocortical tumor. 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 adrenocortical tumors 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 ×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 adrenocortical tumor. Our results suggest that immune responses modulate adrenocortical tumorigenesis and may allow the refinement of risk stratification and treatment for this disease. Clin Cancer Res; 22(24); 6247–55. ©2016 AACR.

Introduction Down syndrome (DS) was first reported in 1866 [1], but likely recognized much earlier [2, 3]. DS is caused by an extra copy of chromosome 21 (whole or partial) and is the most common chromosomal abnormality in the live newborn, with a prevalence estimated at 1 in 644–733 births in the United States [4, 5]. This prevalence will likely change because of delayed maternity, which is associated with increased risk of DS [6], and because of simpler and less invasive prenatal diagnosis of DS [7, 8]. Patients with DS have numerous consistent and variable clinical presentations that include mental retardation, characteristic facies, congenital heart defects, and gastrointestinal abnormalities. The hematologic abnormalities associated with DS and their diagnostic features are detailed in this chapter. Hematologic abnormalities in the DS newborn DS newborns can have transient thrombocytopenia, polycythemia, or neutrophilia. They rarely present with unexplained thrombocytosis, anemia, or neutropenia [5], which are most likely unrelated to DS. Synonyms Currently, no one has coined a unique term for this phenomenon and it is usually referred to descriptively as hematologic abnormalities in the newborn/neonates with DS [5, 9, 10]. This chapter will use the term hematologic abnormalities in the newborn with DS (HANDS) . Epidemiology Up to 80%, 66%, and 34% of DS newborns have neutrophilia, thrombocytopenia, and polycythemia, respectively [5, 9, 10]. These hematological abnormalities spontaneously resolve by three weeks of age [9].