Keratin 34betaE12/keratin7 expression is a prognostic factor of cancer-specific and overall survival in patients with early stage non-small cell lung cancer. (1st February 2016)

• Record Type: Journal Article
• Authors: Pøhl, Mette; Olsen, Karen Ege; Holst, Rene; Donnem, Tom; Busund, Lill-Tove; Bremnes, Roy M.; Al-Saad, Samer; Andersen, Sigve; Richardsen, Elin; Ditzel, Henrik J.; Hansen, Olfred
• Is Part Of: Acta oncologica. Volume 55:Number 2(2016)
• Page Start: 167
• Page End: 177
• Publication Date: 2016-02-01
• Subjects: Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.992
• DOI: 10.3109/0284186X.2015.1049291
• Languages: English
• ISSNs: 0284-186X

Abstract

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.