PDGFRA 突变胃肠道间质瘤中存在间变性淋巴瘤激酶表达可能与不良预后相关。

Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis.

机构信息

Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

出版信息

World J Surg Oncol. 2023 Apr 29;21(1):138. doi: 10.1186/s12957-023-03019-4.

DOI:10.1186/s12957-023-03019-4

PMID:37120571

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10148552/

Abstract

BACKGROUND

Anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several mesenchymal tumors, with significant implications for diagnosis, therapy and prognosis. However, few studies have investigated the correlation between ALK expression status and clinicopathological characteristics in patients with gastrointestinal stromal tumors (GISTs).

METHODS

A total of 506 GIST patients were enrolled. Sanger sequencing was employed to detect c-KIT and PDGFRA gene mutations. The tissue microarray (TMA) technique and immunohistochemistry were employed to identify the ALK (clone: 1A4 and D5F3) expression status in the tumor tissues. The ALK gene variants of IHC-positive cases were analyzed by fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). The clinicopathological data were analyzed using SPSS Statistics 26.0.

RESULTS

Among the 506 GIST patients, the c-KIT mutation accounted for 84.2% (426/506), followed by PDGFRA mutation (10.3%, 52/506), while the wild-type accounted for the least (5.5%, 28/506). ALK-positive expression was detected in PDGFRA-mutant GISTs (7.7%, 4/52) but negative for c-KIT-mutant or wild-type GISTs by IHC. Four ALK IHC-positive patients were all male. The tumors all occurred outside the stomach. The predominant patterns of growth were epithelioid (2/4), spindle (1/4), and mixed type (1/4). They were all identified as high-risk classification according to the National Institutes of Health (NIH) classification. Aberrant ALK mutations were not identified by DNA-based NGS except in one of the 4 cases with amplification by FISH.

CONCLUSION

Our study revealed 7.7% (4/52) of ALK expression in PDGFRA-mutant GISTs, indicating that molecular tests were required to rule out the possibility of PDGFRA-mutant GISTs when encountering ALK-positive mesenchymal tumors with CD117-negative or weakly positive in immunohistochemical staining.

摘要

背景

间变性淋巴瘤激酶 (ALK) 过表达和基因改变已在几种间叶肿瘤中被检测到，这对诊断、治疗和预后具有重要意义。然而，很少有研究调查 ALK 表达状态与胃肠道间质瘤 (GIST) 患者的临床病理特征之间的相关性。

方法

共纳入 506 例 GIST 患者。采用 Sanger 测序检测 c-KIT 和 PDGFRA 基因突变。应用组织微阵列 (TMA) 技术和免疫组织化学法检测肿瘤组织中 ALK (克隆：1A4 和 D5F3) 的表达状态。对免疫组化阳性病例的 ALK 基因变异采用荧光原位杂交 (FISH) 和下一代测序 (NGS) 进行分析。采用 SPSS Statistics 26.0 分析临床病理数据。

结果

在 506 例 GIST 患者中，c-KIT 突变占 84.2% (426/506)，其次是 PDGFRA 突变 (10.3%，52/506)，野生型占比最少 (5.5%，28/506)。ALK 阳性表达在 PDGFRA 突变型 GIST 中被检测到 (7.7%，4/52)，但在 c-KIT 突变型或野生型 GIST 中免疫组化结果为阴性。4 例 ALK 免疫组化阳性患者均为男性。肿瘤均发生于胃外。生长模式主要为上皮样 (2/4)、梭形 (1/4) 和混合性 (1/4)。根据美国国立卫生研究院 (NIH) 分类，它们均被鉴定为高风险分类。除 1 例通过 FISH 检测到扩增外，基于 DNA 的 NGS 未检测到异常的 ALK 突变。