RESUMEN
IDH2 R172 mutations occur in >80% sinonasal undifferentiated carcinomas ("SNUC") and ~80% of these are R172S and R172T variants. We examined the utility of the monoclonal antibody 11C8B1 to IDH2 R172S in IDH2 R172-mutated tumors to establish an immunohistochemistry protocol as a surrogate method for IDH2 R172S mutation detection. Eighty-eight formalin-fixed paraffin-embedded tumors including 42 sinonasal tumors and a variety of IDH1/2-mutated malignancies were tested by immunohistochemistry. The IDH1/2 mutation status was determined in 86 cases by a targeted massively parallel sequencing MSK-IMPACTTM assay. Interestingly, monoclonal antibody 11C8B1 was reactive with all IDH2 R172S (N = 15) mutated tumors including 12 sinonasal carcinomas, 2 high-grade sarcomas and one intrahepatic cholangiocarcinoma, and with all R172T (N = 3) mutated sinonasal carcinomas displaying a distinct granular cytoplasmic labeling in all R172S/T mutated malignancies. 11C8B1 immunohistochemistry was also positive in 2 of 6 IDH1 R132S-mutated tumors, including one intrahepatic cholangiocarcinoma and one chondrosarcoma showing a smooth homogeneous cytoplasmic staining pattern. All IDH2 R172G/K/M/W (N = 22) and IDH1 132H/C/G/L (N = 15) mutated tumors, and all IDH1/2-wild-type tumors (N = 25), including a histologic variety of 23 sinonasal tumors, were immunonegative. Importantly, 11 sinonasal undifferentiated carcinomas (N = 14, 79%) and 3 (100%) high-grade neuroendocrine carcinomas, large cell type were 11C8B1 immunopositive. Literature search revealed a virtual absence of IDH2 R172 and IDH1 R132S mutations in >1000 cases of 8 different malignancies included in the differential diagnosis of sinonasal undifferentiated carcinoma. Our study suggests that positive IDH2 11C8B1 immunohistochemistry in sinonasal carcinomas would be highly predictive of the presence of IDH2 R172S/T mutations and could serve as a reliable adjunct diagnostic marker of sinonasal undifferentiated carcinomas in >70% cases.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/diagnóstico , Análisis Mutacional de ADN/métodos , Isocitrato Deshidrogenasa/genética , Neoplasias del Seno Maxilar/diagnóstico , Anticuerpos Monoclonales , Biomarcadores de Tumor/análisis , Carcinoma/genética , Femenino , Humanos , Inmunohistoquímica/métodos , Isocitrato Deshidrogenasa/análisis , Masculino , Neoplasias del Seno Maxilar/genética , Persona de Mediana Edad , MutaciónRESUMEN
T lymphocytes can be distinguished based on the composition of the T-cell receptor (TCR) chain in α/ß T cells and γ/δ T cells. Correspondingly, α/ß lymphomas can be distinguished from γ/δ lymphomas. The latter are rare neoplasms, which are usually confined to particular organs and tissues and carry a dismal prognosis. Until recently, monoclonal antibody (mAb) clone g3.20 to the TCR γ-chain was the reagent of choice for the immunohistochemical detection of γ/δ T cells and lymphomas in standard formalin-fixed paraffin-embedded tissues. However, due to technical problems, mAb g3.20 became recently unavailable. Our attempts to identify another commercially available clone to the TCR γ-chain were unsuccessful. However, we were able to identify a mAb (clone H-41, SC-100289; Santa Cruz, Dallas, TX) to the TCR δ-chain. H-41 works well in immunohistochemistry on paraffin-embedded tissue and comparison with previously stained cases, shows superior immunolabeling to mAb g3.20. H-41 to the TCR δ-chain appears to be a suitable reagent for the replacement of mAb g3.20.