Journal
JOURNAL OF GASTROENTEROLOGY
Volume 53, Issue 11, Pages 1186-1195Publisher
SPRINGER JAPAN KK
DOI: 10.1007/s00535-018-1464-0
Keywords
Intratumoral HER2 heterogeneity; Trastuzumab; Predictive marker; Chemotherapy; Gastric cancer
Categories
Funding
- JSPS Kakenhi [JP15K10123]
- Daiwa Securities Health Foundation
- Grants-in-Aid for Scientific Research [15K10123] Funding Source: KAKEN
Ask authors/readers for more resources
Background There is growing interest in the clinical significance of intratumoral HER2 heterogeneity. Its prognostic and predictive impacts on trastuzumab efficacy were demonstrated in breast cancer. However, its clinical significance in gastric cancer is still unclear. Methods Twenty-eight HER2-positive gastric cancer patients who had gastrectomy prior to trastuzumab-based chemotherapy were consecutively enrolled. Intratumoral HER heterogeneity was evaluated using whole-tissue sections by immunohistochemistry. When all tumor cells overexpressed HER2 protein, the tumor was defined as homogeneously HER2 (Homo-HER2)-positive group. The others were defined as heterogeneously HER2 (Hetero-HER2)-positive group. Results There was no significant difference in clinicopathological features between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the Homo-HER2-positive group were significantly longer than those in the Hetero-HER2-positive group (PFS; 20.0 months [95% CI 17.8-22.2] vs. 6.0 months [95% CI 2.3-9.7]; HR 0.11; 95% CI 0.03-0.41; p<0.001, OS; not reached vs. 14.0 months [95% CI 11.9-16.1]; HR 0.18; 95% CI 0.06-0.61; p=0.003). In the multivariate analysis, these associations remained significant both in PFS (HR 0.12; 95% CI 0.03-0.46, p=0.002) and OS (HR 0.21; 95% CI 0.06-0.72, p=0.013). With respect to response rate, no statistical difference was found between two groups. However, deeper tumor shrinkage was obtained in the Homo-HER2-positive group compared with the Hetero-HER2-positive group (p=0.046). Conclusions Intratumoral HER2 heterogeneity may have robust clinical impact on trastuzumab efficacy in patients with HER2-positive gastric cancer. These findings should be validated by larger independent cohorts and further molecular correlative analyses are warranted.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available