Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma
Abstract Background Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, an...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13000-020-01045-4 |
| _version_ | 1828453974897852416 |
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| author | Hong Kyu Lee Mi Jung Kwon Yong Joon Ra Hee Sung Lee Hyoung Soo Kim Eun Sook Nam Seong Jin Cho Hye-Rim Park Soo Kee Min Jinwon Seo Ji-Young Choe Kyueng-Whan Min So Young Kang |
| author_facet | Hong Kyu Lee Mi Jung Kwon Yong Joon Ra Hee Sung Lee Hyoung Soo Kim Eun Sook Nam Seong Jin Cho Hye-Rim Park Soo Kee Min Jinwon Seo Ji-Young Choe Kyueng-Whan Min So Young Kang |
| author_sort | Hong Kyu Lee |
| collection | DOAJ |
| description | Abstract Background Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. Methods We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. Results PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002). Conclusions PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up. |
| first_indexed | 2024-12-11T00:15:34Z |
| format | Article |
| id | doaj.art-beb5b378f7e44d7188ec9053f3150f7c |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-12-11T00:15:34Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-beb5b378f7e44d7188ec9053f3150f7c2022-12-22T01:27:59ZengBMCDiagnostic Pathology1746-15962020-10-0115111210.1186/s13000-020-01045-4Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinomaHong Kyu Lee0Mi Jung Kwon1Yong Joon Ra2Hee Sung Lee3Hyoung Soo Kim4Eun Sook Nam5Seong Jin Cho6Hye-Rim Park7Soo Kee Min8Jinwon Seo9Ji-Young Choe10Kyueng-Whan Min11So Young Kang12Department of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Thoracic and Cardiovascular Surgery, Hallym University Dongtan Sacred Heart Hospital, Hallym University Medical CenterDepartment of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Kangdong Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of MedicineDepartment of Pathology, Hanyang University Guri Hospital, Hanyang University College of MedicineDepartment of Pathology, Samsung Medical Center, Sungkyunkwan University College of MedicineAbstract Background Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. Methods We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. Results PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002). Conclusions PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.http://link.springer.com/article/10.1186/s13000-020-01045-4Programmed death-ligand 1EsophagusSquamous cell carcinomaMicrosatellite instabilityHuman papillomavirusPIK3CA |
| spellingShingle | Hong Kyu Lee Mi Jung Kwon Yong Joon Ra Hee Sung Lee Hyoung Soo Kim Eun Sook Nam Seong Jin Cho Hye-Rim Park Soo Kee Min Jinwon Seo Ji-Young Choe Kyueng-Whan Min So Young Kang Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma Diagnostic Pathology Programmed death-ligand 1 Esophagus Squamous cell carcinoma Microsatellite instability Human papillomavirus PIK3CA |
| title | Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma |
| title_full | Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma |
| title_fullStr | Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma |
| title_full_unstemmed | Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma |
| title_short | Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma |
| title_sort | significance of druggable targets pd l1 kras braf pik3ca msi and hpv on curatively resected esophageal squamous cell carcinoma |
| topic | Programmed death-ligand 1 Esophagus Squamous cell carcinoma Microsatellite instability Human papillomavirus PIK3CA |
| url | http://link.springer.com/article/10.1186/s13000-020-01045-4 |
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