Both the serum AFP test and AFP/GPC3/SALL4 immunohistochemistry are beneficial for predicting the prognosis of gastric adenocarcinoma

Bingzhi Wang,Yanling Yuan,Xiuyun Liu,Ning Lu,Zhuo Li,Xiaohao Zheng,Yibin Xie,Liyan Xue,Li Zheng,Jia Gao

doi:10.1186/s12876-021-01986-0

Abstract

BackgroundBoth gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared.MethodsWe collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients’ clinicopathological characteristics and prognoses.ResultsSeventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P < 0.001), perineural spread (P = 0.008), and metastases or recurrence (P < 0.001). For immunohistochemistry, 34 (8.08%) cases were GAPEP, and GAPEP cases also had later pT categories than nGAPEP cases (P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%).ConclusionBoth the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.

Highlights

Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses
In 1970, Bourreille et al proposed the concept of hepatoid adenocarcinoma (HAC) based on morphology and found that this subtype was often accompanied by elevated serum alpha-fetoprotein (sAFP) and more likely to have liver metastases [4, 5]
Clinicopathological characteristics in group A According to sAFP level, 404 (96.19%) cases were assigned to the serum AFP-normal (sAFP-N) group, and 17 (3.81%) cases were assigned to the serum AFP-high (sAFP-H) group (Table 1)

Summary

Introduction

Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. Successive studies concluded that regardless of whether there was a special pathological morphology, cases of positive AFP immunohistochemistry or elevated sAFP had a suggestive risk of progression, collectively referred to as "AFP-producing gastric adenocarcinoma" [8, 9]. This concept suggests transformation from morphology to molecular biology. Patients expressing at least one of these proteins (AFP, GPC3 or SALL4) had a poor prognosis and frequently exhibited liver metastases regardless of morphology They called this subtype “gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP)” [10]

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Conclusion