Mette Pøhl1,2,3, Karen Ege Olsen2,4, Rene Holst5, Tom Donnem6,7, Lill-Tove Busund8,9, Roy M Bremnes6,7, Samer Al-Saad8,9, Sigve Andersen6,7, Elin Richardsen8,9, Henrik J Ditzel1,10, Olfred Hansen1,2. 1. a Department of Oncology , Odense University Hospital , Odense , Denmark. 2. b Institute of Clinical Research, University of Southern Denmark , Odense , Denmark. 3. f Department of Oncology , Rigshospitalet , Copenhagen , Denmark. 4. c Department of Pathology , Odense University Hospital , Odense , Denmark. 5. d Department of Statistics , University of Southern Denmark , Odense , Denmark. 6. g Institute of Clinical Medicine, University of Tromso , Tromso , Norway. 7. h Department of Oncology , University Hospital of North Norway , Tromso , Norway. 8. i Institute of Medical Biology, University of Tromso , Tromso , Norway. 9. j Department of Clinical Pathology , University Hospital of North Norway , Tromso , Norway. 10. e Department of Cancer and Inflammation Research , Institute of Molecular Medicine, University of Southern Denmark , Odense , Denmark.
Abstract
BACKGROUND: Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLC patients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7+, 168 months vs. 34βE12+/K7+, 73 months vs. 34βE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34βE12+/K7+ (HR 1.90) and 34βE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34βE12+/K7 + and 34βE12+/K7 + status was significantly associated with poor overall survival (p < 0.05). CONCLUSION: Keratin 34βE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLC patients with poor cancer-specific and overall survival.
BACKGROUND:Carcinomas and their metastases often retain the keratin patterns of their epithelial origin, and are therefore useful as lineage-specific markers in diagnostic pathology. Recently, it has become clear that intermediate filaments composed by keratins play a role in modulation of cell proliferation, migration, and possibly cancer invasion, factors impacting prognosis in early stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Tumor tissue from a retrospective Danish cohort of 177 patients with completely resected NSCLC, stage I-IIIA tumors, were analyzed for keratin 7 (K7) and keratin 34βE12 expression by immunohistochemistry and validated in a comparable independent Norwegian cohort of 276 stage I-IIIA NSCLCpatients. RESULTS: Based on keratin 34βE12/K7 expression, three subgroups with significantly different median cancer-specific survival rates were identified (34βE12+/K7+, 168 months vs. 34βE12+/K7+, 73 months vs. 34βE12-/K7+, 30 months; p = 0.0004). In multivariate analysis, stage II-IIIA (HR 2.9), 34βE12+/K7+ (HR 1.90) and 34βE12-/K7+ (HR 3.7), were prognostic factors of poor cancer-specific survival (CSS) (p < 0.001). Validation in the Norwegian cohort confirmed that stage II-IIIA (HR 2.3), 34βE12+/K7+ (HR 1.6), and 34βE12-/K7+ (HR 2.0) were prognostic factors of poor CSS (p < 0.05). Multivariate Cox proportional-hazard analysis demonstrated that 34βE12+/K7 + and 34βE12+/K7 + status was significantly associated with poor overall survival (p < 0.05). CONCLUSION: Keratin 34βE12/K7 expression is a prognostic parameter in resected early stage NSCLC that allows identification of high-risk NSCLCpatients with poor cancer-specific and overall survival.
Authors: Arthur Jochems; Issam El-Naqa; Marc Kessler; Charles S Mayo; Shruti Jolly; Martha Matuszak; Corinne Faivre-Finn; Gareth Price; Lois Holloway; Shalini Vinod; Matthew Field; Mohamed Samir Barakat; David Thwaites; Dirk de Ruysscher; Andre Dekker; Philippe Lambin Journal: Acta Oncol Date: 2017-10-14 Impact factor: 4.089