Immunohistochemical correlates of recurrent genetic alterations in sarcomas

Abstract

Accurate diagnosis of sarcomas relies on the integration of clinical, histopathological and molecular features. Our understanding of the latter has increased dramatically in recent years with the application of high‐throughput sequencing. Concomitantly, the role of immunohistochemistry has expanded as genomic alterations have been exploited by the development of diagnostic markers that serve as surrogates for their detection. Herein, we review selected immunohistochemical markers that can infer the presence of diverse molecular events. These include gene fusions in vascular neoplasms (FOSB, CAMTA1 and TFE3), round cell sarcomas (BCOR, DUX4 and WT1), and fibroblastic/myofibroblastic tumors (STAT6, ALK and Pan‐TRK); amplifications in well‐differentiated and dedifferentiated liposarcomas (MDM2 and CDK4); and deletions in several aggressive neoplasms (SMARCB1 and SMARCA4). Protein correlates of single nucleotide variants (beta‐catenin in desmoid fibromatosis) and epigenetic alterations (histone H3K27me3 in malignant peripheral nerve sheath tumor) and markers discovered through gene expression profiling (NKX2.2 and MUC4) are also discussed.

Case of the month 1-2019: CNS high-grade neuroepithelial tumor with BCOR alteration

“…Immunohistochemically, all tumors showed a strong NCAM and vimentin immunoreactivity as well as a weaker EGFR expression, whereas all other markers (GFAP, Olig2, desmin, myogenin, synaptophysin, EMA, CD34, NeuN, pan- cytokeratin (AE1/AE3), cytokeratin 8/18, IDH1-R132H, S100 protein, Lin28A, nuclear β-catenin) were not expressed. An anti-BCOR antibody revealed strong nuclear immunolabeling of the cells, which has been also reported in PMMT, round cell sarcomas, and CCSK [1, 12]. Yoshida et al [16] described 5 cerebellar and 1 temporal tumors emphasizing the uniform character of the tumor cells with a stellate-shape appearance and fibrillary processes.…”

Congenital mesoblastic nephroma is characterised by kinase mutations including EGFR internal tandem duplications, the ETV6–NTRK3 fusion, and the rare KLHL7–BRAF fusion

“…Although direct identification of mutations with molecular techniques is ideal, many histopathology laboratories in hospitals may not have easy access to such techniques in the clinical setting, especially for mutations in rare tumours such as CMN. However, immunohistochemistry (IHC) can be a surrogate method for identifying specific mutations 15 …”

Resultados del tratamiento quirúrgico de sarcomas de partes blandas en adultos

“…La sobrevida global con el tratamiento instaurado fue del 86,4%. pérdida de la tinción nuclear con histone 3 lysine 27 trimethylation (H3K27me3) 9,12,13 . Finalmente, las pruebas de diagnóstico molecular se aplican actualmente para contribuir al diagnóstico en grupos seleccionados de sarcomas, como los relacionados con translocaciones 9,10 .…”

“…Marcadores de diferenciación miogénica como la desmina, la actina músculo liso (SMA) y la actina músculo específico (MSA) se expresan en LMS y rabdomiosarcomas (RMS). Los marcadores de diferenciación endotelial como CD31 y CD34 se expre san en el angiosarcoma, y los marcadores de diferenciación neural, como el S100, en el TMVNP epitelioide 11,12 Actualmente existen nuevos marcadores inmunohistoquímicos basados en alteraciones genéticas moleculares, como en el liposarcoma bien diferenciado y desdiferenciado, que presenta una tinción nuclear con murine double minutes (MDM2) y el tumor maligno de la vaina del nervio periférico, que evidencia una que hace que se presenten con tumores muy avanzados, con prolongado tiempo de evolución.…”