Alpha-Fetoprotein (AFP) and Gastric Cancer: Why is Lethality More Prevalent in AFP-Secreting than NonSecreting Tumors?

Gastric cancer (GC), a heterogenous adenocarcinoma of the stomach, is the fourth most common cancer and the second cause of cancer death worldwide [1]. Alpha-fetoprotein (AFP) secreting GC (AFP(+) GC is quite different from the conventional stomach cancer (AFP(-) GC) being more aggressive, having lower patient survival times, and prone to liver/lymph node metastasis [2]. Another subtype of GCs, termed the Signet Ring cell gastric carcinoma, originates in the stomach glandular cells, produces mucin and ERBB2 (an oncogenic receptor), and is histopositive for AFP and its cell surface receptor [3]. A third subtype of GC is hepatoid cancer (HC) of the stomach which mimics a hepatocellular carcinoma. The HC is also a high AFP(+) secreting stomach cancer characterized by lymphadenopathy, liver metastasis, and venous tumor thrombosis [4-6]. The AFP(+)GC is an aggressive, highly malignant, metastatic, fast progressing tumor with a poor prognosis. No standard therapy is currently available for patients with AFP(+)GC although several multi-modal therapies have been reported [2]. These modalities include surgery, chemotherapeutics, drugs, and interventative and molecular targeted therapies. The chemo-drug therapies have encompassed;