Immunohistochemical Expression of GLUT1 and its Correlation with Unfavorable Histology and TP53 Codon 72 Polymorphism in Wilms Tumors

• Published in: Pediatric and developmental pathology Vol. 15; no. 4; pp. 286 - 292
• Main Authors: Rakheja, Dinesh, Khokhar, Shama, Mitui, Midori, Cost, Nicholas G.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-07-2012; SAGE PUBLICATIONS, INC
• Subjects: Adolescent; Child; Child, Preschool; Female; Glucose Transporter Type 1 - metabolism; Humans; Immunoenzyme Techniques; Infant; Kidney Neoplasms - diagnosis; Kidney Neoplasms - genetics; Kidney Neoplasms - metabolism; Male; Neoplasm Staging; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Prognosis; Tissue Array Analysis; Tumor Suppressor Protein p53 - genetics; Wilms Tumor - diagnosis; Wilms Tumor - genetics; Wilms Tumor - metabolism; anaplasia; GLUT1; TP53; Wilms tumor
• ISSN: 1093-5266; 1615-5742
• DOI: 10.2350/12-01-1151-OA.1

Reprogramming of energy metabolism, such as increased glycolysis, is a hallmark of cancer cells. One mechanism by which cancer cells fuel glycolysis is through increased uptake of glucose across cell membranes via the glucose transporter GLUT1. One of the transcriptional repressors of GLUT1 is wild-type TP53, and cancer-associated loss of function mutations within the DNA-binding domain of TP53 impairs the repressive effect of TP53 on transcriptional activity of the GLUT1 gene promoter. Because TP53 mutations are associated with unfavorable histology (diffuse anaplasia) in Wilms tumors, we hypothesized increased expression of GLUT1 in these tumors. To evaluate this hypothesis, we performed tissue microarray–based immunohistochemistry for GLUT1 in a set of 50 Wilms tumors, including 5 with unfavorable histology. In a subset of 16 favorable histology Wilms tumors, we compared the GLUT1 immunoexpression with TP53 codon 72 polymorphism status. We found consistently stronger immunoexpression of GLUT1 in unfavorable histology Wilms tumors compared to favorable histology Wilms tumors (P = 0.04). We noted that the favorable histology Wilms tumors with a proline residue at position 72 of TP53 tended to have higher immunoexpression of GLUT1, although this immunoexpression did not reach statistical significance in this small set of cases. In summary, our finding of strong GLUT1 immunoexpression in unfavorable histology Wilms tumors indicates that these tumors are likely to be 2-deoxy-2-(18F)fluoro-D-glucose avid and that GLUT1 should be evaluated as a therapeutic target for these tumors that otherwise show resistance to conventional therapy.