Shinji Sumiyoshi1, Akihiko Yoshizawa2, Makoto Sonobe3, Masashi Kobayashi3, Motoki Sato4, Masakazu Fujimoto1, Tatsuaki Tsuruyama1, Hiroshi Date3, Hironori Haga1. 1. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. 2. Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan; Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan. Electronic address: akyoshi@shinshu-u.ac.jp. 3. Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan. 4. Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
Abstract
OBJECTIVES: The characteristics of non-terminal respiratory unit (TRU) type lung adenocarcinoma are still unclear. The aim of the present study was to characterize non-TRU type lung adenocarcinoma. MATERIALS AND METHODS: We analyzed the expression of mucins MUC5B and MUC5AC, as well as thyroid transcription factor-1 (TTF-1), using a tissue microarray comprising lung adenocarcinoma specimens from 244 consecutive patients. The presence of mutations in EGFR and KRAS were also determined. RESULTS: TTF-1, MUC5B, and MUC5AC were detected in 219 (89.8%), 75 (30.7%), and 33 cases (13.5%), respectively. Cluster analysis of protein expression profiles and EGFR and KRAS mutations yielded five groups of tumors as follows: TRU1-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(-)]; TRU2-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(+)]; Combined-type [TTF-1(+), MUC5B(+), and/or MUC5AC(+)]; Bronchiolar-type [TTF-1(-), MUC5B(+) and/or MUC5AC(+)]; and Null-type [TTF-1(-), MUC5B(-), MUC5AC(-), EGFR mutations(-), KRAS mutations(-)]. TRU-type tumors, which include TRU1- and TRU2-type tumors, were significantly associated with TRU morphology, whereas Bronchiolar-type tumors were associated with non-TRU morphology. Combined-type cases exhibited intermediate morphologies between TRU-type and Bronchiolar-type cases. TRU-type was associated with significantly better prognosis, followed by Combined-type, Bronchiolar-type, and Null-type (disease-free survival [DFS] P = 0.017; overall survival [OS], P = 0.002). Multivariate analyses indicated that non-TRU type tumors, which include Bronchiolar-, Combined-, Null-type tumors, were significantly correlated with poorer prognoses for DFS (hazard ratio = 1.785; 95% CI, 1.041-3.063; P = 0.035) and OS (hazard ratio = 1.928; 95% CI, 1.084-3.421; P = 0.025). CONCLUSION: This study revealed three distinct subtypes of non-TRU type adenocarcinomas. Additionally, non-TRU type tumors were associated with worse prognoses than TRU type tumors. The results presented here may be useful for select patients should appropriate therapies become available.
OBJECTIVES: The characteristics of non-terminal respiratory unit (TRU) type lung adenocarcinoma are still unclear. The aim of the present study was to characterize non-TRU type lung adenocarcinoma. MATERIALS AND METHODS: We analyzed the expression of mucins MUC5B and MUC5AC, as well as thyroid transcription factor-1 (TTF-1), using a tissue microarray comprising lung adenocarcinoma specimens from 244 consecutive patients. The presence of mutations in EGFR and KRAS were also determined. RESULTS:TTF-1, MUC5B, and MUC5AC were detected in 219 (89.8%), 75 (30.7%), and 33 cases (13.5%), respectively. Cluster analysis of protein expression profiles and EGFR and KRAS mutations yielded five groups of tumors as follows: TRU1-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(-)]; TRU2-type [TTF-1(+), MUC5B(-), MUC5AC(-), EGFR mutations(+)]; Combined-type [TTF-1(+), MUC5B(+), and/or MUC5AC(+)]; Bronchiolar-type [TTF-1(-), MUC5B(+) and/or MUC5AC(+)]; and Null-type [TTF-1(-), MUC5B(-), MUC5AC(-), EGFR mutations(-), KRAS mutations(-)]. TRU-type tumors, which include TRU1- and TRU2-type tumors, were significantly associated with TRU morphology, whereas Bronchiolar-type tumors were associated with non-TRU morphology. Combined-type cases exhibited intermediate morphologies between TRU-type and Bronchiolar-type cases. TRU-type was associated with significantly better prognosis, followed by Combined-type, Bronchiolar-type, and Null-type (disease-free survival [DFS] P = 0.017; overall survival [OS], P = 0.002). Multivariate analyses indicated that non-TRU type tumors, which include Bronchiolar-, Combined-, Null-type tumors, were significantly correlated with poorer prognoses for DFS (hazard ratio = 1.785; 95% CI, 1.041-3.063; P = 0.035) and OS (hazard ratio = 1.928; 95% CI, 1.084-3.421; P = 0.025). CONCLUSION: This study revealed three distinct subtypes of non-TRU type adenocarcinomas. Additionally, non-TRU type tumors were associated with worse prognoses than TRU type tumors. The results presented here may be useful for select patients should appropriate therapies become available.
Authors: Alison K Bauer; Misha Umer; Vanessa L Richardson; Amber M Cumpian; Anna Q Harder; Nasim Khosravi; Zoulikha Azzegagh; Naoko M Hara; Camille Ehre; Maedeh Mohebnasab; Mauricio S Caetano; Daniel T Merrick; Adrie van Bokhoven; Ignacio I Wistuba; Humam Kadara; Burton F Dickey; Kalpana Velmurugan; Patrick R Mann; Xian Lu; Anna E Barón; Christopher M Evans; Seyed Javad Moghaddam Journal: JCI Insight Date: 2018-08-09
Authors: Tamás Zombori; Tibor Nyári; László Tiszlavicz; Regina Pálföldi; Edit Csada; Tibor Géczi; Aurél Ottlakán; Balázs Pécsy; Gábor Cserni; József Furák Journal: Virchows Arch Date: 2018-04-02 Impact factor: 4.064