IMP dehydrogenase rod/ring structures in acral melanomas

Author(s)

Keppeke, Gerson D. ^[1] ; Barcelos, Denise ^[2] ; Fernandes, Mariana ^[2] ; Comodo, Andreia N. ^[2] ; Guimaraes, Daiane P. ^[2] ; Cardili, Leonardo ^[2] ; Carapeto, Fernando C. L. ^[2] ; Andrade, Luis E. C. ^[1] ; Landman, Gilles ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Rheumatol Div, Escola Paulista Med, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Pathol, Escola Paulista Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: PIGMENT CELL & MELANOMA RESEARCH; JAN 2020.
• Web of Science Citations: 0

Abstract

Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p <.001). Histopathology showed that 71% of the RR-positive specimens presented Breslow thickness > 4.0mm, compared with only 29% in the RR-low/negative (p =.039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy. (AU)

• FAPESP's process: 17/20745-1 - Autoantibodies depletion on autoreactive plasmocytes by genome editing with the CRISPR/Cas9 system
• Grantee: Gerson Dierley Keppeke
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/10547-8 - Evaluation of heterogeneity of BRAF, MAP2K1 and MAP2K2 in primary and metastatic melanomas
• Grantee: Gilles Landman
• Support Opportunities: Regular Research Grants