Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Lui, Vivian Wai Yan; To, Ka‐Fai; Lo, Kwok Wai

doi:10.1002/cncr.31131

Cancer

2017

DOI: 10.1002/cncr.31131

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Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Vivian Wai Yan Lui

Ka‐Fai To

Kwok Wai Lo

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Cited by 2 publications

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“…Such patients were overwhelmingly in need of systemic therapy and had advanced and/or recurrent disease. As such, the setting of a nonendemic area and among patients with diverse ethnic backgrounds adds substantial variance to the clinicopathologic characteristics of patients in the series, in contrast to the previous work on patients with nasopharyngeal carcinoma (NPC) …”

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confidence: 98%

Reply to Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Ali¹,

Ross²,

Wang

2017

Cancer

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confidence: 98%

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Ali¹,

Ross²,

Wang

2017

Cancer

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Immunohistochemical Detection and Molecular Characterization of IDH-mutant Sinonasal Undifferentiated Carcinomas

Mito¹,

Bishop

Sadow

et al. 2018

American Journal of Surgical Pathology

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Recent studies have identified recurrent isocitrate dehydrogenase 2 (IDH2) mutations in a subset of sinonasal undifferentiated carcinomas (SNUCs); however, the true frequency of IDH mutations in SNUC is unknown. We evaluated the utility of mutation-specific IDH1/2 immunohistochemistry (IHC) in a large multi-institutional cohort of SNUC and morphologic mimics. IHC using a multispecific antibody for IDH1/2 (R132/R172) mutant protein was performed on 193 sinonasal tumors including: 53 SNUCs, 8 poorly differentiated carcinomas (PDCARs) and 132 histologic mimics. Mutant IDH1/2 IHC was positive in 26/53 SNUCs (49%; 20 strongly positive and 6 weak) and 3/8 PDCARs (37.5%; 2 strong; 1 weak) but was absent in all other tumor types (0/132). Targeted next-generation sequencing (NGS) on a subset of SNUC/PDCAR (6 strong and 3 weak positive for IDH1/2 IHC; 7 negative) showed frequent IDH2 R172X mutations (10/16) and a single IDH1 R132C mutation. All 6 cases with strong positive mutant IDH1/2 staining and NGS had IDH2 R172S/G mutations. The 3 IHC-weak cases all had IDH2 R172T mutations. Among the 7 tested cases that were negative for mutant IDH1/2 IHC, NGS detected 1 case each with IDH2 R172T and IDH1 R132C mutation. IDH-mutant carcinomas also had frequent mutations in TP53 (55%) and activating mutations in KIT (45%) or the PI3K pathway (36%). Mutation-specific IDH1/2 IHC identifies IDH mutations in SNUC, however, it lacks sensitivity for the full range of IDH mutations. These findings suggest that IDH-mutant sinonasal carcinoma may represent a distinct pathobiological entity with therapeutic implications that can be identified by a combined approach of multispecific IDH1/2 IHC and sequencing.

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Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Cited by 2 publications

References 9 publications

Reply to Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Reply to Genomic profiles of nasopharyngeal carcinoma: The importance of histological subtyping and Epstein‐Barr virus in situ assays

Immunohistochemical Detection and Molecular Characterization of IDH-mutant Sinonasal Undifferentiated Carcinomas

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