학술논문
Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.
Document Type
Academic Journal
Author
Kawai H; Department of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.; Department of Diagnostic Pathology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.; Miura T; Department of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.; Kawamatsu N; Department of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.; Department of Diagnostic Pathology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.; Nakagawa T; Department of Diagnostic Pathology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.; Shiba-Ishii A; Department of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan.; Yoshimoto T; Department of Pathology, Showa General Hospital, 8-1-1 Hanakoganei, Kodaira-Shi, Tokyo, 187-851, Japan.; Amano Y; Department of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.; Kihara A; Department of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.; Sakuma Y; Department of Molecular Medicine, Sapporo Medical University, 1-17, Minami Chuo-Ku, Sapporo, Hokkaido, 060-8556, Japan.; Fujita K; Department of Respiratory Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.; Shibano T; Department of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.; Ishikawa S; Department of Preventive Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.; Ushiku T; Human Pathology Department, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.; Fukayama M; Human Pathology Department, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.; Tsubochi H; Department of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.; Endo S; Department of Thoracic Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsukeshi, Tochigi, 329-0498, Japan.; Hagiwara K; Omiya Medical Association Medical Examination Center, 2-107, Higashioonari-Chou, Kita-Ku, Saitama-Shi, Saitama, 331-8689, Japan.; Matsubara D; Department of Pathology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8574, Japan. matsubarad@md.tsukuba.ac.jp.; Department of Diagnostic Pathology, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan. matsubarad@md.tsukuba.ac.jp.; Department of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. matsubarad@md.tsukuba.ac.jp.; Niki T; Department of Integrative Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Source
Publisher: Springer International Country of Publication: Germany NLM ID: 9423843 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2307 (Electronic) Linking ISSN: 09456317 NLM ISO Abbreviation: Virchows Arch Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear.
Materials and Methods: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression.
Result: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors.
Conclusion: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.
(© 2024. The Author(s).)
Materials and Methods: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression.
Result: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors.
Conclusion: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.
(© 2024. The Author(s).)