Prognostic Significance of Major Histocompatibility Complex Class II Expression in Pediatric Adrenocortical Tumors: A St. Jude and Children's Oncology Group Study.
OBJECTIVE
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.


METHODS
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.
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Emilia Modolo
EM
Pinto
International Outreach, St. Jude Children's Research Hospital, Memphis, Tennessee.
Carlos
C
Rodriguez-Galindo
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
John Kim
JK
Choi
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Stanley
S
Pounds
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Zhifa
Z
Liu
Hartwell Center, St. Jude Children's Research Hospital, Memphis, Tennessee.
Geoffrey
G
Neale
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
David
D
Finkelstein
Department of Pathology, Texas Children's Hospital, Houston, Texas.
John M
JM
Hicks
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Alberto S
AS
Pappo
Instituto de Pesquisa Pelé Pequeno Príncipe and Faculdades Pequeno Príncipe, Curitiba, Brazil.
Bonald C
BC
Figueiredo
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. gerard.zambetti@stjude.org raul.ribeiro@stjude.org.
Raul C
RC
Ribeiro
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. gerard.zambetti@stjude.org raul.ribeiro@stjude.org.
Gerard P
GP
Zambetti
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis
D015415:Biomarkers; D000949:Histocompatibility Antigens Class II