Department of Pathology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, China.
Department of Pathology, Shanghai Children's Medical Centre, Shanghai, China.
Histopathology. 2020 Oct;77(4):611-621. doi: 10.1111/his.14194. Epub 2020 Sep 10.
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).
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.
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.
先天性中胚层肾瘤（CMN）在组织学上分为经典型、细胞型和混合型。本研究旨在描述一系列 CMN 的临床、病理和分子特征，并确定泛 Trk 和表皮生长因子受体（EGFR）免疫组化作为 NTRK 基因融合和 EGFR 内部串联重复（ITD）替代标志物的效用。
使用逆转录聚合酶链反应（PCR）和基于下一代测序的锚定多重 PCR，对 22 例存档的 CMN 病例（12 例经典型、5 例细胞型和 5 例混合型）进行 ETV6-NTRK3 融合和 EGFR ITD 转录本的检测。所有 12 例经典型 CMN 均有 EGFR ITD。在 5 例细胞型 CMN 中，有 4 例存在 ETV6-NTRK3 融合，1 例存在 KLHL7-BRAF 融合。在 5 例混合型 CMN 中，有 4 例存在 EGFR ITD，1 例存在 ETV6-NTRK3 融合。泛 Trk 免疫组化对 NTRK 重排的存在具有 100%的敏感性和 94.1%的特异性。然而，EGFR 染色对 EGFR ITD 的敏感性仅为 62.5%，特异性为 33.3%。
EGFR ITD 是经典型 CMN 中一致的遗传事件。大多数细胞型 CMN 存在 ETV6-NTRK3 融合。罕见的细胞型 CMN 可能存在非典型突变，如在 1 例中发现的 KLHL7-BRAF 融合。混合型 CMN 可能存在 EGFR ITD 或 ETV6-NTRK3 融合。泛 Trk 免疫组化是 NTRK 重排的一种敏感但非特异性标志物。EGFR 免疫组化对 EGFR ITD 无帮助。
