PMID- 37120571 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20230502 IS - 1477-7819 (Electronic) IS - 1477-7819 (Linking) VI - 21 IP - 1 DP - 2023 Apr 29 TI - Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis. PG - 138 LID - 10.1186/s12957-023-03019-4 [doi] LID - 138 AB - 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. CI - (c) 2023. The Author(s). FAU - Wu, Ying AU - Wu Y AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Gao, Beibei AU - Gao B AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Xia, Qin AU - Xia Q AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Zhu, Yili AU - Zhu Y AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Wang, Na AU - Wang N AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Chang, Xiaona AU - Chang X AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Huang, Bo AU - Huang B AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Luo, Danju AU - Luo D AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Zhang, Jiwei AU - Zhang J AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Zhang, Peng AU - Zhang P AD - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Shi, Heshui AU - Shi H AD - Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. FAU - Fan, Jun AU - Fan J AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. fanjun0915@sina.com. FAU - Nie, Xiu AU - Nie X AD - Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China. whunhpath@163.com. LA - eng GR - 2020CFB808/Natural Science Foundation of Hubei Province/ GR - 81773022/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230429 PL - England TA - World J Surg Oncol JT - World journal of surgical oncology JID - 101170544 RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) SB - IM MH - Male MH - Humans MH - *Gastrointestinal Stromal Tumors/pathology MH - Anaplastic Lymphoma Kinase/genetics MH - In Situ Hybridization, Fluorescence MH - Mutation MH - Proto-Oncogene Proteins c-kit/genetics MH - Prognosis MH - Receptor, Platelet-Derived Growth Factor alpha/genetics PMC - PMC10148552 OTO - NOTNLM OT - ALK expression OT - Clinicopathological features OT - Gastrointestinal stromal tumor COIS- The authors declare no competing interests. EDAT- 2023/04/30 00:42 MHDA- 2023/05/01 10:17 PMCR- 2023/04/29 CRDT- 2023/04/29 23:17 PHST- 2022/12/13 00:00 [received] PHST- 2023/04/23 00:00 [accepted] PHST- 2023/05/01 10:17 [medline] PHST- 2023/04/30 00:42 [pubmed] PHST- 2023/04/29 23:17 [entrez] PHST- 2023/04/29 00:00 [pmc-release] AID - 10.1186/s12957-023-03019-4 [pii] AID - 3019 [pii] AID - 10.1186/s12957-023-03019-4 [doi] PST - epublish SO - World J Surg Oncol. 2023 Apr 29;21(1):138. doi: 10.1186/s12957-023-03019-4.