The Clinicopathological Characteristics of Alpha-Fetoprotein-Producing Adenocarcinoma of the Gastrointestinal Tract—A Single-Center Retrospective Study

Abstract

Alpha-fetoprotein (AFP)-producing adenocarcinoma from the gastrointestinal tract (APA-GI) is a rare type of highly malignant tumor with a poor prognosis. It may originate from any site along the GI tract with similar clinicopathological characteristics. As limited research had ever described the characteristics of APA-GI, the present article intends to systemically investigate the clinicopathological characteristics of APA-GI from a single center's retrospective study to deepen the understanding of the disease. A total of 177 patients pathologically diagnosed with APA-GI between 2010 and 2017 at the Second Affiliated Hospital of Zhejiang University, School of Medicine, were included. Also, clinical data of 419 gastric cancers and 609 colorectal cancers from The Cancer Genome Atlas database were also extracted. Clinical information of patients from Second Affiliated Hospital of Zhejiang University, School of Medicine, was collected, and a median follow-up of 14.5 months was performed to investigate clinical characteristics of APA-GI. For the pathological characteristics of APA-GI, hematoxylin–eosin sections were reviewed, and immunohistochemistry of AFP was performed. The results showed that the primary tumor could develop through the whole GI tract, including the esophagus (0.6%), stomach (83.1%), duodenum (1.1%), ileum (0.6%), appendix (0.6%), colon (5.1%), and rectum (7.9%). Hepatoid adenocarcinoma is the main pathological feature of APA-GI. AFP expression level in tumor tissue was not strictly associated with serum AFP or hepatoid differentiation. The prognosis of APA-GI was worse than that of common adenocarcinoma of the GI tract and liver metastasis, and high AFP levels suggest poor prognosis in patients with APA-GI. Therefore, the present study was the first research to systemically explore the clinicopathological characteristics of APA-GI. APA-GI occurs through the whole GI tract with a significantly worse prognosis than common adenocarcinoma of GI. APA-GI should be regarded as one kind of disease for its similar clinicopathological characteristics within patients.

Effect of immune checkpoint inhibitors in patients with gastric hepatoid adenocarcinoma: a case report and literature review

“…3,19 As a specific tumor biomarker, AFP is an oncofetal protein produced by the fetal liver, gastrointestinal cells, and yolk sac, and AFP is widely used in the diagnosis of yolk cyst tumors, hepatoblastomas, and HCC. 3,20 Recent studies have shown that AFP is also frequently highly-expressed in other human tumors, such as those of enteroblastic GC, colorectal cancer, gallbladder cancer, lung cancer, and ovarian cancer, of which GHAC is the most common. 6,21,22 Clinically, advanced GC patients with liver metastasis or chronic hepatitis B also have elevated serum AFP.…”

Clinical Implications of Circulating Circular RNAs in Lung Cancer

“…Some circRNAs can be expressed differently in tissues, although their serum levels are not significantly different. As in the case of alpha-fetoprotein in hepatocellular carcinoma, one of the most intensively studied cancer biomarkers [83], even though circRNA candidates are upregulated or downregulated in cancer tissues compared with non-cancer tissues, the difference between their plasma or serum levels in patients and healthy controls may not be apparent. These circRNAs are not suitable for diagnosing or predicting diseases in a non-invasive manner [51].…”

A “conversion‐deterioration‐double mutation” theory for the evolution and progression of colorectal cancer

“… 26 Hepatoid adenocarcinoma is the main pathological feature of alpha‐fetoprotein (AFP) CRC. 27 In the view of our “conversion‐deterioration‐double mutation” theory, it can be explained that CSCs (regardless of origin from stem cells or de‐differentiation of CRC cells) undergo an aberrant differentiation process and produce hepatic‐cancer‐like CRC cells, and these cells share the feature of secreting AFP, thus expressing an AFP‐producing pattern. Morphologically, they look like hepatic cancer cells and can adapt to the liver microenvironment well; therefore, they are more prone to liver metastasis.…”

“…AFP‐producing CRC has poor differentiation and shows aggressive biological behavior and worse prognosis than traditional CRC 26 . A high metastasis rate and liver metastasis are the main characteristics of AFP‐producing CRC at initial diagnosis, 27 and synchronous distant metastasis is commonly observed 26 . Hepatoid adenocarcinoma is the main pathological feature of alpha‐fetoprotein (AFP) CRC 27 .…”

“…A high metastasis rate and liver metastasis are the main characteristics of AFP‐producing CRC at initial diagnosis, 27 and synchronous distant metastasis is commonly observed 26 . Hepatoid adenocarcinoma is the main pathological feature of alpha‐fetoprotein (AFP) CRC 27 . In the view of our “conversion‐deterioration‐double mutation” theory, it can be explained that CSCs (regardless of origin from stem cells or de‐differentiation of CRC cells) undergo an aberrant differentiation process and produce hepatic‐cancer‐like CRC cells, and these cells share the feature of secreting AFP, thus expressing an AFP‐producing pattern.…”