https://scholars.lib.ntu.edu.tw/handle/123456789/494580
標題: | Phosphorylated insulin-like growth factor-1 receptor (pIGF1R) is a poor prognostic factor in brain metastases from lung adenocarcinomas | 作者: | Wu P.-F. Huang W.-C. CHIH-HSIN YANG YEN-SHEN LU JIN-YUAN SHIH SHANG-GIN WU CHING-HUNG LIN ANN-LII CHENG |
公開日期: | 2013 | 卷: | 115 | 期: | 1 | 起(迄)頁: | 61-70 | 來源出版物: | Journal of Neuro-Oncology | 摘要: | A greater understanding of brain metastases is imperative for developing novel therapeutic strategies. Our previous study showed that insulin-like growth factor (IGF) signaling pathway was activated in brain-tropic cancer cells. In this study, we investigated the clinical relevance of activated (phosphorylated) IGF-1 receptor (pIGF1R) expression in brain metastases originating from lung adenocarcinomas. All pathologically confirmed brain metastases from lung adenocarcinomas, with available archived specimens from January 1998 to December 2009 at National Taiwan University Hospital, were assessed immunohistochemically for pIGF1R expression using H-score criteria. A median H-score was used as a cutoff point to define high or low pIGF1R expression. The mutation status in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) was examined using direct sequencing. The prognostic significance of pIGF1R expression, its correlations with clinicopathological characteristics, and EGFR status were evaluated. In the 86 cases, high membranous/cytoplasmic pIGF1R expression in brain metastases correlated with a shorter median survival (10.8 vs 27.8 mo, P = 0.003). This correlation was more significant in patients with EGFR mutations [hazard ratio (HR) 2.38, 95 % confidence interval (CI) 1.19-4.77 for EGFR mutations; HR 1.99, 95 % CI 0.95-4.15 for EGFR wild type] and remained statistically significant in multivariate analysis after adjusting for the effects of other potential prognostic factors, including the graded prognostic assessment score, solitary brain metastasis, extracranial metastatic status, EGFR mutations, and treatment using EGFR tyrosine kinase inhibitors. Although we also identified nuclear pIGF1R expression, this result was prognostically non-significant. Our study results showed that high membranous/cytoplasmic pIGF1R expression in brain metastases was a poor prognostic factor, more significantly in patients with EGFR mutations than in those with wild-type EGFRs. ? 2013 Springer Science+Business Media New York. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885478933&doi=10.1007%2fs11060-013-1194-3&partnerID=40&md5=be37e53804e1e03ba528118626255dc5 https://scholars.lib.ntu.edu.tw/handle/123456789/494580 |
ISSN: | 0167-594X | DOI: | 10.1007/s11060-013-1194-3 | SDG/關鍵字: | epidermal growth factor receptor; epidermal growth factor receptor kinase inhibitor; somatomedin C receptor; adult; aged; article; brain metastasis; brain radiation; cancer prognosis; cancer radiotherapy; cancer surgery; cancer survival; controlled study; epidermal growth factor receptor gene; female; gene; gene mutation; H score; human; human tissue; immunohistochemistry; lung adenocarcinoma; major clinical study; male; neurosurgery; overall survival; protein expression; protein function; protein phosphorylation; scoring system; survival prediction; survival time; Adenocarcinoma; Aged; Brain Neoplasms; Carcinoma, Adenosquamous; Carcinoma, Large Cell; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Mutation; Neoplasm Staging; Phosphorylation; Prognosis; Receptor, Epidermal Growth Factor; Receptor, IGF Type 1; Survival Rate; Tumor Markers, Biological |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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