Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis
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 clin...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | World Journal of Surgical Oncology |
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| Online Access: | https://doi.org/10.1186/s12957-023-03019-4 |
| _version_ | 1827956786071601152 |
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| author | Ying Wu Beibei Gao Qin Xia Yili Zhu Na Wang Xiaona Chang Bo Huang Danju Luo Jiwei Zhang Peng Zhang Heshui Shi Jun Fan Xiu Nie |
| author_facet | Ying Wu Beibei Gao Qin Xia Yili Zhu Na Wang Xiaona Chang Bo Huang Danju Luo Jiwei Zhang Peng Zhang Heshui Shi Jun Fan Xiu Nie |
| author_sort | Ying Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T15:09:26Z |
| format | Article |
| id | doaj.art-e2f6b10db1064193bc3830be0a06a4d8 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-04-09T15:09:26Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-e2f6b10db1064193bc3830be0a06a4d82023-04-30T11:18:10ZengBMCWorld Journal of Surgical Oncology1477-78192023-04-012111910.1186/s12957-023-03019-4Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosisYing Wu0Beibei Gao1Qin Xia2Yili Zhu3Na Wang4Xiaona Chang5Bo Huang6Danju Luo7Jiwei Zhang8Peng Zhang9Heshui Shi10Jun Fan11Xiu Nie12Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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.https://doi.org/10.1186/s12957-023-03019-4Gastrointestinal stromal tumorALK expressionClinicopathological features |
| spellingShingle | Ying Wu Beibei Gao Qin Xia Yili Zhu Na Wang Xiaona Chang Bo Huang Danju Luo Jiwei Zhang Peng Zhang Heshui Shi Jun Fan Xiu Nie Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis World Journal of Surgical Oncology Gastrointestinal stromal tumor ALK expression Clinicopathological features |
| title | Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| title_full | Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| title_fullStr | Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| title_full_unstemmed | Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| title_short | Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| title_sort | anaplastic lymphoma kinase expression in pdgfra mutated gastrointestinal stromal tumors probably correlates with poor prognosis |
| topic | Gastrointestinal stromal tumor ALK expression Clinicopathological features |
| url | https://doi.org/10.1186/s12957-023-03019-4 |
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