Abstract 1560: Correlation of FAP(fibroblast activation protein)-expressing cancer associated fibroblasts (CAFs) and tumor metastasis in esophageal carcinoma

Abstract

Abstract Background: The tumor and its microenvironment have dynamic interactions and signaling that strongly affect tumor progression. Cancer associated fibroblasts (CAFs) are activated fibroblasts and thought to be an important player in the tumor microenvironment. Although there are several indicators of CAF, fibroblast activation protein (FAP) is unique in its selectivity for CAFs in comparison with other markers. The aim of this study is to investigate CAFs expressing FAP and its relationship to cancer metastasis in esophageal cancer. Methods: Sections of paraffin-embedded resected primary human esophageal cancer specimens from 2008 through 2010 in Okayama University hospital were stained with antibody directed against FAP. Overall percentage of stromal FAP staining of the primary tumor was assessed semi-quantitatively (0, 1, 2, 3, 4, 5) and staining intensity was also graded (none, weak, intermediate, strong). Survival time and time to recurrence data were analyzed using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. Results: 49 patients with resected specimens were available for study with 26 (53.1%) stage I, 8 (16.3%) stage II, 14 (28.6%) stage III, and 1 (2.0%) stage IV patients. All patients were divided to 2 groups, FAP high group and FAP low group, which are 25 patients (51%) and 24 (49%) respectively. The cutoff for subgroups was defined at the median value. FAP (immune) expression at tumoral stroma was a significant predictive factor for lymph node metastasis (p<0.01) and vessel invasion (p<0.01). In survival analysis of DFS (disease free survival) and OS (overall survival), FAP high stroma was associated with shorter period to recurrence (p<0.05) and death (p<0.05) than those of FAP low stroma. Conclusions: Our clinicopathological analysis indicates that patients whose esophageal carcinoma have high levels of stromal FAP expression are more likely to have an aggressive disease progression and a potential development of metastases and recurrence. Although therapeutic strategies targeting the tumor cells have been generally inadequate in esophageal carcinomas yet, here we announce that a stroma-targeted therapy should be considered. Now we are ongoing to evaluate metastatic potential of CAFs in vitro and vivo, in order to elucidate the function of FAP expressing CAFs and, in future to establish a novel therapeutic strategy. Citation Format: Hajime Kashima, Kazuhiro Noma, Yuki Katsura, Takuya Kato, Ryoichi Katsube, Takayuki Ninomiya, Toshiaki Ohara, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Correlation of FAP(fibroblast activation protein)-expressing cancer associated fibroblasts (CAFs) and tumor metastasis in esophageal carcinoma. [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 1560.