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原发肿瘤、淋巴结转移灶与库肯勃瘤中 RTK 基因状态的对比研究。

A comparative study of RTK gene status between primary tumors, lymph-node metastases, and Krukenberg tumors.

机构信息

Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, Hangzhou, Zhejiang Province, China.

Department of Pathology and Pathophysiology, College of Medicine, Zhejiang University, 310058, Hangzhou, Zhejiang Province, China.

出版信息

Mod Pathol. 2021 Jan;34(1):42-50. doi: 10.1038/s41379-020-0636-7. Epub 2020 Jul 30.

Abstract

Krukenberg tumor (KT) refers to a rare ovarian tumor that has metastasized from a primary site. Patients with KTs have a poorer prognosis and worse survival. Thus far, little is known about the frequency of receptor tyrosine kinase (RTK) gene amplification and the concordance of gene amplification between primary tumors, lymph-node metastases, and KTs. Herein, 50 paired samples, including primary cancers, metastatic lymph nodes, and KTs were collected, and RTK gene amplification was tested by fluorescence in situ hybridization (FISH). There were four cases positive for human epidermal growth factor receptor type 2 (HER2) amplification, all of which showed conversion of HER2 status between different lesions. Of the two cases with c-mesenchymal-epithelial transition (c-MET) amplification, the primary tumors and lymph nodes were negative while the right involved ovaries were positive. Inconsistent fibroblast growth factor receptor 2 (FGFR2) status in different lesions was observed in three of the six FGFR2-amplified cases. Co-amplification of RTK genes was identified in only one patient for primary cancer and two for KTs. Collectively, there were 46, 48, 50, and 44 cases negative for HER2, c-MET, EGFR, and FGFR2 amplification in all lesions, respectively. There was no significant difference in overall survival between KTs of gastric origin and colorectal origin. However, of all synchronous cancers, KTs of colorectal origin had a better prognosis than those of gastric origin. In conclusion, the positive rate of RTK gene amplification in KTs was low. Intratumoral heterogeneity was frequent in KTs with RTK gene amplification. A mutually exclusive pattern of RTK gene amplification was dominant in primary cancers, lymph-node metastases, and KTs. There was no survival difference between KTs of gastric origin and colorectal origin. However, of all synchronous cancers, KTs of colorectal origin had a better prognosis than those of gastric origin.

摘要

克鲁根伯格瘤(Krukenberg tumor,KT)是一种罕见的卵巢转移瘤,原发灶多来自胃肠道。KT 患者预后较差,生存时间较短。目前,关于受体酪氨酸激酶(receptor tyrosine kinase,RTK)基因扩增的频率以及原发灶、淋巴结转移灶和 KT 之间基因扩增的一致性知之甚少。本研究收集了 50 对包括原发灶、转移淋巴结和 KT 的配对样本,采用荧光原位杂交(fluorescence in situ hybridization,FISH)检测 RTK 基因扩增。有 4 例人表皮生长因子受体 2(human epidermal growth factor receptor type 2,HER2)扩增阳性,均为不同部位 HER2 状态转换。2 例间质上皮转化(mesenchymal-epithelial transition,MET)扩增中,原发灶和淋巴结均为阴性,而右侧受累卵巢为阳性。在 6 例 FGFR2 扩增中,有 3 例不同部位 FGFR2 状态不一致。仅在 1 例原发灶和 2 例 KT 中发现 RTK 基因共扩增。HER2、c-MET、EGFR 和 FGFR2 在所有病变中均阴性的病例分别为 46、48、50 和 44 例。胃来源和结直肠来源的 KT 患者的总生存率无显著差异。然而,在所有同步癌中,结直肠来源的 KT 预后优于胃来源的 KT。总之,KT 中 RTK 基因扩增的阳性率较低。在具有 RTK 基因扩增的 KT 中,肿瘤内异质性较为常见。在原发灶、淋巴结转移灶和 KT 中,RTK 基因扩增呈相互排斥模式。胃来源和结直肠来源的 KT 患者的生存时间无差异。然而,在所有同步癌中,结直肠来源的 KT 预后优于胃来源的 KT。

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