title: Expression of hepatocyte growth factor and c-Met is characteristic of α-fetoprotein-producing colorectal adenocarcinoma: A report of three cases.
abstract: α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma.
authors: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang 310009, P.R. China.
authors: Jun
authors: J
authors: Li
authors: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang 310009, P.R. China.
authors: Yue
authors: Y
authors: Liu
authors: Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang 310009, P.R. China; Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors: Jing-Hong
authors: JH
authors: Xu
authors: Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors: Zheng-Ping
authors: ZP
authors: Xu
authors: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang 310009, P.R. China.
authors: Shu
authors: S
authors: Zheng
authors: Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang 310009, P.R. China.
authors: Ke-Feng
authors: KF
authors: Ding
keywords: colorectal cancer; hepatocyte differentiation; α-fetoprotein