Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma
Takahiro Amano,
Hideki Iijima,
Shinichiro Shinzaki,
Taku Tashiro,
Shuko Iwatani,
Mizuki Tani,
Yuriko Otake,
Takeo Yoshihara,
Aya Sugimoto,
Satoshi Egawa,
Shinjiro Yamaguchi,
Kazuo Kinoshita,
Manabu Araki,
Motohiro Hirao,
Yuko Sakakibara,
Satoshi Hiyama,
Hiroyuki Ogawa,
Koji Nagaike,
Jun Murata,
Masato Komori,
Yorihide Okuda,
Takashi Kizu,
Yoshiki Tsujii,
Yoshito Hayashi,
Takahiro Inoue,
Hidekazu Takahashi,
Tsunekazu Mizushima,
Eiichi Morii,
Tetsuo Takehara
Affiliations
Takahiro Amano
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Hideki Iijima
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Shinichiro Shinzaki
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Taku Tashiro
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Shuko Iwatani
Department of Internal Medicine, Osaka Police Hospital
Mizuki Tani
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Yuriko Otake
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Takeo Yoshihara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Aya Sugimoto
Department of Gastroenterology, Toyonaka Municipal Hospital
Satoshi Egawa
Department of Internal Medicine, Osaka Police Hospital
Shinjiro Yamaguchi
Department of Gastroenterology, Kansai Rosai Hospital
Kazuo Kinoshita
Department of Gastroenterology, Otemae Hospital
Manabu Araki
Department of Gastroenterology, National Hospital Organization Osaka Minami Medical Center
Motohiro Hirao
Department of Gastroenterology and Hepatology, Osaka Rosai Hospital
Yuko Sakakibara
Department of Gastroenterology, National Hospital Organization Osaka National Hospital
Satoshi Hiyama
Department of Gastroenterology, Japan Community Healthcare Organization Osaka Hospital
Hiroyuki Ogawa
Department of Gastroenterology, Nishinomiya Municipal Central Hospital
Koji Nagaike
Department of Gastroenterology and Hepatology, Suita Municipal Hospital
Jun Murata
Department of Gastroenterology, Higashiosaka City Medical Center
Masato Komori
Department of Gastroenterology, Hyogo Prefectural Nishinomiya Hospital
Yorihide Okuda
Department of Gastroenterology, Saiseikai Senri Hospital
Takashi Kizu
Department of Gastroenterology, Yao Municipal Hospital
Yoshiki Tsujii
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Yoshito Hayashi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Takahiro Inoue
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Hidekazu Takahashi
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine
Tsunekazu Mizushima
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine
Eiichi Morii
Department of Pathology, Osaka University Graduate School of Medicine
Tetsuo Takehara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine
Abstract Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.