Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma
Abstract Background Hypoxic microenvironment is prominent in advanced esophageal squamous cell carcinoma (ESCC). However, it is unclear whether ESCC becomes hypoxic when it remains in the mucosal layer or as it invades the submucosal layer. We aimed to investigate whether intramucosal (Tis‐T1a) or s...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6217 |
| _version_ | 1797361238154412032 |
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| author | Nobuhisa Minakata Shingo Sakashita Masashi Wakabayashi Yuka Nakamura Hironori Sunakawa Yusuke Yoda Genichiro Ishii Tomonori Yano |
| author_facet | Nobuhisa Minakata Shingo Sakashita Masashi Wakabayashi Yuka Nakamura Hironori Sunakawa Yusuke Yoda Genichiro Ishii Tomonori Yano |
| author_sort | Nobuhisa Minakata |
| collection | DOAJ |
| description | Abstract Background Hypoxic microenvironment is prominent in advanced esophageal squamous cell carcinoma (ESCC). However, it is unclear whether ESCC becomes hypoxic when it remains in the mucosal layer or as it invades the submucosal layer. We aimed to investigate whether intramucosal (Tis‐T1a) or submucosal invasive (T1b) ESCC becomes hypoxic using endoscopic submucosal dissection samples. Methods We evaluated the expression of hypoxia markers including hypoxia inducible factor 1α (HIF‐1α), carbonic anhydrase IX (CAIX), and glucose transporter 1 (GLUT1) by H‐score and vessel density by microvessel count (MVC) and microvessel density (MVD) for CD31 and α‐smooth muscle actin (α‐SMA) with immunohistochemical staining (n = 109). Further, we quantified oxygen saturation (StO2) with oxygen saturation endoscopic imaging (OXEI) (n = 16) and compared them to non‐neoplasia controls, Tis‐T1a, and T1b. Results In Tis‐T1a, cccIX (13.0 vs. 0.290, p < 0.001) and GLUT1 (199 vs. 37.6, p < 0.001) were significantly increased. Similarly, median MVC (22.7/mm2 vs. 14.2/mm2, p < 0.001) and MVD (0.991% vs. 0.478%, p < 0.001) were markedly augmented. Additionally, in T1b, the mean expression of HIF‐1α (16.0 vs. 4.95, p < 0.001), CAIX (15.7 vs. 0.290, p < 0.001), and GLUT1 (177 vs. 37.6, p < 0.001) were significantly heightened, and median MVC (24.8/mm2 vs. 14.2/mm2, p < 0.001) and MVD (1.51% vs. 0.478%, p < 0.001) were markedly higher. Furthermore, OXEI revealed that median StO2 was significantly lower in T1b than in non‐neoplasia (54% vs. 61.5%, p = 0.00131) and tended to be lower in T1b than in Tis‐T1a (54% vs. 62%, p = 0.0606). Conclusion These results suggest that ESCC becomes hypoxic even at an early stage, and is especially prominent in T1b. |
| first_indexed | 2024-03-08T15:51:03Z |
| format | Article |
| id | doaj.art-b3d5dc3af66c4fa0929fbd08be2a6c7a |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T15:51:03Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-b3d5dc3af66c4fa0929fbd08be2a6c7a2024-01-09T05:41:07ZengWileyCancer Medicine2045-76342023-08-011215158091581910.1002/cam4.6217Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinomaNobuhisa Minakata0Shingo Sakashita1Masashi Wakabayashi2Yuka Nakamura3Hironori Sunakawa4Yusuke Yoda5Genichiro Ishii6Tomonori Yano7Department of Gastroenterology and Endoscopy National Cancer Center Hospital East Kashiwa JapanDivision of Pathology Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Kashiwa JapanBiostatistics Division, Center for Research Administration and Support National Cancer Center Kashiwa JapanDepartment of Strategic Programs Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Kashiwa JapanDepartment of Gastroenterology and Endoscopy National Cancer Center Hospital East Kashiwa JapanDepartment of Gastroenterology and Endoscopy National Cancer Center Hospital East Kashiwa JapanCourse of Advanced Clinical Research of Cancer Juntendo University Graduate School of Medicine Bunkyo‐ku JapanDepartment of Gastroenterology and Endoscopy National Cancer Center Hospital East Kashiwa JapanAbstract Background Hypoxic microenvironment is prominent in advanced esophageal squamous cell carcinoma (ESCC). However, it is unclear whether ESCC becomes hypoxic when it remains in the mucosal layer or as it invades the submucosal layer. We aimed to investigate whether intramucosal (Tis‐T1a) or submucosal invasive (T1b) ESCC becomes hypoxic using endoscopic submucosal dissection samples. Methods We evaluated the expression of hypoxia markers including hypoxia inducible factor 1α (HIF‐1α), carbonic anhydrase IX (CAIX), and glucose transporter 1 (GLUT1) by H‐score and vessel density by microvessel count (MVC) and microvessel density (MVD) for CD31 and α‐smooth muscle actin (α‐SMA) with immunohistochemical staining (n = 109). Further, we quantified oxygen saturation (StO2) with oxygen saturation endoscopic imaging (OXEI) (n = 16) and compared them to non‐neoplasia controls, Tis‐T1a, and T1b. Results In Tis‐T1a, cccIX (13.0 vs. 0.290, p < 0.001) and GLUT1 (199 vs. 37.6, p < 0.001) were significantly increased. Similarly, median MVC (22.7/mm2 vs. 14.2/mm2, p < 0.001) and MVD (0.991% vs. 0.478%, p < 0.001) were markedly augmented. Additionally, in T1b, the mean expression of HIF‐1α (16.0 vs. 4.95, p < 0.001), CAIX (15.7 vs. 0.290, p < 0.001), and GLUT1 (177 vs. 37.6, p < 0.001) were significantly heightened, and median MVC (24.8/mm2 vs. 14.2/mm2, p < 0.001) and MVD (1.51% vs. 0.478%, p < 0.001) were markedly higher. Furthermore, OXEI revealed that median StO2 was significantly lower in T1b than in non‐neoplasia (54% vs. 61.5%, p = 0.00131) and tended to be lower in T1b than in Tis‐T1a (54% vs. 62%, p = 0.0606). Conclusion These results suggest that ESCC becomes hypoxic even at an early stage, and is especially prominent in T1b.https://doi.org/10.1002/cam4.6217blood vesselendoscopyesophageal squamous cell carcinomahypoxianeoplasm invasion |
| spellingShingle | Nobuhisa Minakata Shingo Sakashita Masashi Wakabayashi Yuka Nakamura Hironori Sunakawa Yusuke Yoda Genichiro Ishii Tomonori Yano Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma Cancer Medicine blood vessel endoscopy esophageal squamous cell carcinoma hypoxia neoplasm invasion |
| title | Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| title_full | Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| title_fullStr | Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| title_full_unstemmed | Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| title_short | Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| title_sort | immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma |
| topic | blood vessel endoscopy esophageal squamous cell carcinoma hypoxia neoplasm invasion |
| url | https://doi.org/10.1002/cam4.6217 |
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