Development of a novel HER2 test based on the therapeutic antibody trastuzumab = 치료용 항체 트라스투주맙을 이용한 새로운 HER2 테스트의 개발

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Despite the use of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), the response rate of trastuzumab monotherapy remains approximately 50%. Here, we developed a novel test, Trastuzumab IHC, that uses unmodified trastuzumab and IHC procedures to identify patients whose tumors were found to be HER2-positive by the HercepTest or FISH analysis, but who did not respond to trastuzumab therapy. The Trastuzumab IHC test was performed on HER2-negative/-positive cell lines, including trastuzumab-sensitive (SK-BR-3)/resistant (JIMT-1) breast cancer cell lines. We also applied the Trastuzumab IHC on 133 consecutive primary breast cancer tumors and 12 needle biopsied specimens who received trastuzumab pre-operatively. Then, the results were compared with those obtained from the HercepTest and FISH analysis. The Trastuzumab IHC is the only test that could distinguish the JIMT-1 from SK-BR-3 cell lines in terms of HER2 expression. With 133 tumor specimens, only 4% (2/50) of the cases who were HercepTest 2+ and FISH (-) were positive on the Trastuzumab IHC test. In addition, 48.5% (16/33) of the FISH (+) cases were confirmed to be positive by Trastuzumab IHC. This result is consistent with the clinical benefit rate of trastuzumab in patients with FISH-positive results. The Trastuzumab IHC is 24.8% more accurate and 52.1% more specific at predicting HER2 gene amplification by FISH than positive staining with the HercepTest. Also, positive predictive value for Trastuzumab IHC (88.9%) was higher than the HercepTest (39.8%). Furthermore, among 12 patients who received trastuzumab pre-operatively, two patients who did not responded to trastuzumab therapy were negative for the Trastuzumab IHC test. In conclusion, the Trastuzumab IHC test has a high specificity and positive predictive value, which can be used to predict patient responses to trastuzumab therapy.
Advisors
Koh, Gou-Youngresearcher고규영researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2010
Identifier
419047/325007  / 020088005
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2010.2, [ v, 45 p. ]

Keywords

Trastuzumab; HER2 test; Breast cancer; Immunohistochemistry(IHC); 면역조직화학염색; 트라스투주맙; 허투 테스트; 유방암

URI
http://hdl.handle.net/10203/28113
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=419047&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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