In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4931-4931
Abstract:
Although HER2 immunohistochemistry (IHC) is widely used to assess the HER2 status, not all patients could be clarified with HER2 IHC positivity for Trastuzumab treatment. Here, we introduce a novel IHC method utilizing Trastuzumab itself; compared to conventional HER2 IHC, the new method evaluates the extracellular epitope which is the target of action for Trastuzumab. The purpose of this study is to test whether this new method has better performance in predicting treatment outcome of Trastuzumab therapy, and whether it is the significant prognostic factor in consecutive gastric cancer patients. From two individual institutions, 37 and 32 GC patients treated with Trastuzumab were enrolled respectively, the former as the training cohort and the latter for validation, and progression free survivals (PFS) were compared according to the results of Trastuzumab IHC. To validate the prognostic significance of Trastuzumab IHC in consecutive GC, we constructed tissue microarrays (TMA) from 536 consecutive cases and Trastuzumab IHC, HER2 IHC, and HER2 silver in situ hybridization (SISH) were performed. In training cohort (n = 37), all cases were HER2 IHC 2+ (n = 11) or 3+ (n = 26), but 2+ in 3 cases (8.1%) and 3+ in 10 cases (27.0%) by Trastuzumab IHC. Similar results were observed in validation cohort, 17 of 32 cases (53.1%) were 2+ or 3+ by Trastuzumab IHC. Trastuzumab ≥2+ group in the training cohort had significantly better PFS than Trastuzumab & lt;2+ group (p = 0.016), and survival analysis of PFS in validation cohort and combined cohort also showed favorable PFS in Trastuzumab ≥2+ group (p = 0.031 and 0.001, respectively). By Cox regression analysis in training cohort, Trastuzumab IHC ≥2+ was proved to be the independent predictive factor for PFS in patients receiving Trastuzumab. Of 536 consecutive cases of GC, 23 (4.3%) were HER2 IHC 3+, and among these patients, only 5 (21.7%) were also 3+ by Trastuzumab IHC. Disease specific survival (DSS) and overall survival (OS) in Trastuzumab IHC ≥2+ group were shorter compared to Trastuzumab IHC & lt;2 group (p = 0.015 and 0.063, respectively), while both HER2 IHC and HER2 SISH failed to discriminate significant survival differences between subgroups. In this study, we demonstrated that Trastuzumab IHC is a significant predictive factor for PFS in Trastuzumab-treated GC patients, and poor prognostic factor of DSS in consecutive GC, even better than conventional HER2 IHC and HER2 SISH. We believe that Trastuzumab IHC is a very promising, relatively easy-to-implement, novel method to assess HER2 status in routine clinical practice. Citation Format: Jiwon Koh, Soo Kyung Nam, Younwoo Lee, Chan-Young Ock, Jin Won Kim, Keun-Wook Lee, Do-Youn Oh, Do Joong Park, Hyung-Ho Kim, Keon-Wook Kang, Woo Ho Kim, Ho-Young Lee, Hye Seung Lee. Validation of Trastuzumab immunohistochemistry as a predictive and prognostic biomarker in gastric cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4931.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-4931
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
