Prognostic value of ALK overexpression and molecular abnormalities in high-grade serous ovarian carcinoma.

IF 2.2 4区医学 Q3 ONCOLOGY

Cancer Biomarkers Pub Date : 2023-01-01 DOI:10.3233/CBM-230117

Adam Gorczyński, Kevin Miszewski, Yann Gager, Sonja Koch, Jane Pötschke, Dimitar Ugrinovski, Jörg Gabert, Agata Pospieszyńska, Dariusz Wydra, Renata Duchnowska, Bartosz Szymanowski, Szczepan Cierniak, Irene Kruecken, Karsten Neumann, Katarina Mirkov, Wojciech Biernat, Piotr Czapiewski

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引用次数: 0

Abstract

Background: ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear.

Objective: To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC.

Methods: Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes.

Results: ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC.

Conclusions: HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.

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高级别浆液性卵巢癌中ALK过表达及分子异常的预后价值。

背景:ALK受体酪氨酸激酶(ALK receptor tyrosine kinase, ALK)畸变在许多肿瘤的发病机制中都有明确的作用，但其在高级别浆液性卵巢癌(HGSOC)中的临床意义尚不清楚。目的:分析HGSOC患者ALK过表达频率、ALK分子异常及其对无进展生存期(PFS)和总生存期(OS)的影响。方法:采用免疫组化(IHC)方法检测3个不同克隆抗alk抗体的蛋白表达。利用荧光原位杂交分析易位的存在。下一代测序用于研究拷贝数变异，以及涉及其他常见重排基因的点突变和易位。结果:高达52%的肿瘤显示ALK过表达，而8.2%的肿瘤显示ALK拷贝增加，对生存无明显影响。13例肿瘤(8.9%)发现ALK点突变，其中3例属于IV类，OS明显改善。在这些病例中，还注意到一种趋势表明PFS更好。此外，还发现了三个基因融合:ERBB2-GRB7、PRKCA-BRCA1和SND1-BRAF，这些基因融合在HGSOC中均未被报道。结论:携带活化ALK突变的HGSOC可能与更好的生存率相关，而ALK过表达和ALK扩增不影响预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.