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Congenital mesoblastic nephroma is characterised by kinase mutations including EGFR internal tandem duplications, the ETV6 – NTRK3 fusion, and the rare KLHL7 – BRAF fusion
Author(s) -
Zhao Manli,
Yin Minzhi,
Kuick Chik Hong,
Chen Huiyi,
Aw Sze Jet,
Merchant Khurshid,
Ng Eileen Hui Qi,
Gunaratne Sandini,
Loh Amos Hong Pheng,
Gu Weizhong,
Tang Hongfeng,
Chang Kenneth Tou En
Publication year - 2020
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.14194
Subject(s) - immunohistochemistry , trk receptor , biology , gene rearrangement , fusion gene , cancer research , medicine , pathology , gene , receptor , genetics , neurotrophin
Aims Congenital mesoblastic nephroma (CMN) is histologically classified into classic, cellular and mixed subtypes. The aims of this study were to characterise the clinical, pathological and molecular features of a series of CMNs, and to determine the utility of pan‐Trk and epidermal growth factor receptor (EGFR) immunohistochemistry as surrogate markers for NTRK gene fusions and EGFR internal tandem duplications (ITDs). Methods and results Twenty‐two archival CMN cases (12 classic, five cellular, and five mixed) were tested for the ETV6 – NTRK3 fusion and EGFR ITD transcripts by the use of reverse transcriptase polymerase chain reaction (PCR), and next‐generation sequencing‐based anchored multiplex PCR. All 12 classic CMNs had EGFR ITD. Of the five cellular CMNs, four had the ETV6 – NTRK3 fusion and one had the KLHL7 – BRAF fusion. Of the five mixed CMNs, four had EGFR ITD, and one had the ETV6 – NTRK3 fusion. Pan‐Trk immunoreactivity was 100% sensitive and 94.1% specific for the presence of NTRK rearrangement. However, EGFR staining was only 62.5% sensitive and 33.3% specific for EGFR ITD. Conclusions EGFR ITD is a consistent genetic event in classic CMN. A majority of cellular CMNs have the ETV6 – NTRK3 fusion. Rare cellular CMNs may harbour non‐canonical mutations such as the KLHL7 – BRAF fusion, which was found in one case. Mixed CMNs may have either EGFR ITD or the ETV6 – NTRK3 fusion. Pan‐Trk immunohistochemistry is a sensitive, albeit not perfectly specific, marker for NTRK rearrangement. EGFR immunohistochemistry is not helpful as a marker of EGFR ITD.