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Clinicopathological analysis of ROS1 gene alterations and immunohistochemistry screening for ROS1 gene rearrangement in non-small cell lung cancer
DC Field | Value | Language |
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dc.contributor.advisor | 정진행 | - |
dc.contributor.author | 김연 | - |
dc.date.accessioned | 2017-07-14T01:31:45Z | - |
dc.date.available | 2017-07-14T01:31:45Z | - |
dc.date.issued | 2015-08 | - |
dc.identifier.other | 000000049818 | - |
dc.identifier.uri | https://hdl.handle.net/10371/122062 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 의학과 병리학전공, 2015. 8. 정진행. | - |
dc.description.abstract | Introduction: ROS1 rearrangement, found in a subset of lung cancers, have therapeutic significance, as ROS1-rearranged tumors are sensitive to ALK kinase inhibitors. This study sought to evaluate the clinicopathological implications of ROS1 gene alterations and the histomorphological characteristics of ROS1-rearranged tumors, especially micropapillary and aerogenous spread growth, and to investigate the usefulness of ROS1 immunohistochemistry as a diagnostic test for ROS1 rearrangement.
Methods: Characterization of ROS1 gene alterations using fluorescent in situ hybridization, and characterization of ROS1 and E-cadherin protein expression using immunohistochemistry were performed in 754 non-small cell lung cancer (NSCLC) surgical samples. Results: ROS1 rearrangement was identified in ten patients (1.3%, NSCLC | - |
dc.description.abstract | 1.9%, adenocarcinoma). Histologically, all ten ROS1-rearranged tumors harbored an adenocarcinoma component. Importantly, ROS1 rearrangements were highly associated with micropapillary components (p < 0.001), aerogenous spread status (p = 0.002), and loss of E-cadherin expression (p = 0.049). Kaplan-Meier survival curves with log-rank test showed that ROS1 rearrangement was significantly associated with a higher risk of tumor recurrence (p = 0.024). Nine of the ten ROS1-rearranged tumors showed moderate-to-strong ROS1 immunoreactivity, with a 100?300 H-score range (median, 240), whereas most ROS1 wild-type cancers (73.3%) lacked detectable immunoreactivity (H-score range, 0?240 | - |
dc.description.abstract | median, 0). The criterion that best differentiated between ROS1-rearranged and ROS1 wild-type tumors was an H-score of ≥100, with a sensitivity and specificity of 90% and 93.5%, respectively. On the other hand, ROS1 gene copy number gain (CNG) was found in 4.8% (18/375) of the tumors. ROS1 gene CNG was significantly associated with shorter disease-free survival (DFS, 12 vs. 58 months | - |
dc.description.abstract | p = 0.003) and shorter overall survival (OS, 40 vs. 67 months | - |
dc.description.abstract | p < 0.001) compared to that observed in the group without CNG. Multivariate analysis confirmed that ROS1 gene CNG was significantly associated with poorer DFS (hazard ratio [HR] = 2.16, 95% confidence interval [CI] = 1.22?3.81, p = 0.008), and poorer OS ([HR] = 2.53, 95% [CI] = 1.31?4.89, p = 0.006).
Conclusion: This study demonstrated that ROS1 gene rearrangement was detected in 1.9% of surgically resected adenocarcinoma. The patients harboring ROS1-rearrangement showed shorter DFS. ROS1-rearranged lung adenocarcinoma exhibited distinct morphological and clinicopathological features, including high prevalence of cribriform and/or micropapillary pattern with aerogenous spread status and decreased membranous E-cadherin expression. Cutoff value of H-score 100 best predicts ROS1 rearrangement. On the other hand, ROS1 gene CNG is an independent indicator of poor prognosis in surgically resected NSCLC. | - |
dc.description.tableofcontents | Abstract
Contents List of Tables List of Figures List of Abbreviations and Symbols Introduction Materials and Methods Results Discussion References Tables Figures Abstract in Korean | - |
dc.format | application/pdf | - |
dc.format.extent | 1436170 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | Lung cancer | - |
dc.subject | ROS1 gene alteration | - |
dc.subject | histomorphology | - |
dc.subject | immunohistochemistry | - |
dc.subject.ddc | 610 | - |
dc.title | Clinicopathological analysis of ROS1 gene alterations and immunohistochemistry screening for ROS1 gene rearrangement in non-small cell lung cancer | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.citation.pages | vii, 42 | - |
dc.contributor.affiliation | 의과대학 의학과 | - |
dc.date.awarded | 2015-08 | - |
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