Hong Kyu Lee1, Mi Jung Kwon2, Jinwon Seo3, Jeong Won Kim4, Mineui Hong4, Hye-Rim Park5, Soo Kee Min5, Ji-Young Choe5, Yong Joon Ra1, Seung Hun Jang6, Yong Il Hwang6, Ho Young Kim7, Kyueng-Whan Min8. 1. Department of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Republic of Korea. 2. Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Republic of Korea. Electronic address: mulank99@hallym.or.kr. 3. Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Republic of Korea. Electronic address: jwseomd@hallym.or.kr. 4. Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Daerim 1-Dong, Yeongdeungpo-gu, Seoul, 150-950, Republic of Korea. 5. Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Republic of Korea. 6. Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro 170 beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do, 431-796, Republic of Korea. 7. Department of Hematological Oncology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea. 8. Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Kyoungchun-ro 153, Guri-si, Gyeonggi-do, 11923, Republic of Korea.
Abstract
ALK-positive (ALK+) lung adenocarcinoma usually shows a more advanced-staged disease with frequent nodal metastasis and highly aggressive outcomes compared with EGFR-mutated lung cancers. The aim of this study was to investigate the expression profiles of several mucins in ALK + lung cancers to gain insight into the relationship between the more aggressive biological nature of ALK + lung cancers and the role of mucins. We examined the immunohistochemical profiles of mucins MUC1, MUC2, MUC5AC, and MUC6 in 19 ALK + lung cancers compared with 42 EGFR-mutated lung cancers. ALK + cancers were found to occur in younger patients and were characterized by a solid-predominant histologic subtype with frequent signet ring cells and peritumoral muciphages. By contrast, EGFR-mutated cancers lacked ALK-specific histological patterns. Although all MUC1 and MUC5AC were expressed in both subtypes, MUC1 expression in ALK + cancers was visualized exclusively through cytoplasmic staining, whereas those in EGFR-mutated cancers were predominantly membranous staining in apical area (92.9%) and focally in cytoplasmic staining (7.1%). MUC5AC expression in ALK + cancers was exclusively visualized through cytoplasmic staining (100%), whereas EGFR-mutated cancers showed predominantly perinuclear dot-like patterns (90.5%) and focal cytoplasmic staining (9.5%). MUC2 and MUC6 expression was not detected in either type of lung cancer. CONCLUSIONS: The high frequency of both MUC1 and MUC5AC cytoplasmic expression, coupled with a lack of MUC2 and MUC6 expression in ALK + lung cancer may contribute to the biologically aggressive behavior of ALK + cancer. Inhibitors to these types of mucins may thus act as a barrier to cancerous extension reducing their aggressive behavior.
ALK-positive (ALK+) lung adenocarcinoma usually shows a more advanced-staged disease with frequent nodal metastasis and highly aggressive outcomes compared with EGFR-mutated lung cancers. The aim of this study was to investigate the expression profiles of several mucins in ALK + lung cancers to gain insight into the relationship between the more aggressive biological nature of ALK + lung cancers and the role of mucins. We examined the immunohistochemical profiles of mucins MUC1, MUC2, MUC5AC, and MUC6 in 19 ALK + lung cancers compared with 42 EGFR-mutated lung cancers. ALK + cancers were found to occur in younger patients and were characterized by a solid-predominant histologic subtype with frequent signet ring cells and peritumoral muciphages. By contrast, EGFR-mutated cancers lacked ALK-specific histological patterns. Although all MUC1 and MUC5AC were expressed in both subtypes, MUC1 expression in ALK + cancers was visualized exclusively through cytoplasmic staining, whereas those in EGFR-mutated cancers were predominantly membranous staining in apical area (92.9%) and focally in cytoplasmic staining (7.1%). MUC5AC expression in ALK + cancers was exclusively visualized through cytoplasmic staining (100%), whereas EGFR-mutated cancers showed predominantly perinuclear dot-like patterns (90.5%) and focal cytoplasmic staining (9.5%). MUC2 and MUC6 expression was not detected in either type of lung cancer. CONCLUSIONS: The high frequency of both MUC1 and MUC5AC cytoplasmic expression, coupled with a lack of MUC2 and MUC6 expression in ALK + lung cancer may contribute to the biologically aggressive behavior of ALK + cancer. Inhibitors to these types of mucins may thus act as a barrier to cancerous extension reducing their aggressive behavior.
Authors: Sebastian Dwertmann Rico; Moritz Mahnken; Franziska Büscheck; David Dum; Andreas M Luebke; Martina Kluth; Claudia Hube-Magg; Andrea Hinsch; Doris Höflmayer; Christina Möller-Koop; Christoph Fraune; Katharina Möller; Anne Menz; Christian Bernreuther; Frank Jacobsen; Patrick Lebok; Till S Clauditz; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Ronald Simon; Stefan Steurer; Sarah Minner; Eike Burandt; Till Krech; Andreas H Marx Journal: Technol Cancer Res Treat Date: 2021 Jan-Dec