Clinicopathological And Prognostic Characteristics Of Hepatoid Adenocarcinoma Of The Stomach

BackgroundHepatoid adenocarcinoma(HAC)is a particular type of extrahepatic adenocarcinoma with morphological characteristics similar to hepatocellular carcinoma(HCC).Although elevated serum alpha fetoprotein(AFP)level is an important feature of HAC,it is not detected in all HAC patients.Although stomach is the most common site of HAC occurrence,HAC can also be found in gallbladder,uterus,lung,bladder,esophagus,colon,and ovary.The incidence of hepatoid adenocarcinoma of the stomach(HAS)accounts for only 0.17%to 1%of all gastric cancers.Histopathological features are the gold standard for the diagnosis of HAS.The appearance of hepatocellular differentiation areas in the primary focus of gastric cancer,regardless of the elevated serum AFP or AFP-positive immunohistochemical staining,can be used to diagnose HAS.The clinical symptoms are not identical compared with common gastric adenocarcinoma,while the prognosis of HAS is worse than that of common gastric adenocarcinoma,attributed to its frequent vascular involvement as well as lymph node and liver metastases.Due to the low incidence rate of HAS,the understanding of HAS is still insufficient from a clinical point of view,and missed diagnosis and misdiagnosis easily occur under these circumstances.Therefore,early and accurate diagnosis is a prerequisite to improve the survival of HAS patients.Meanwhile,aggressive multimodal treatment comprising of radical gastrectomy,resection of liver metastases and adjuvant chemotherapy is warranted for HAS therapy.ObjectiveThe aim of this study is to analyze the differences betweent HAS and common gastric adenocarcinoma,and investigate the factors affecting prognosis of HAS.MethodsFrom January 2013 to May 2020,the clinicopathological features and prognosis of 39 patients who were diagnosed as HAS in the First Affiliated Hospital of Zhengzhou University were evaluated.In addition,78 stage-matched patients with common gastric adenocarcinoma were selected as controls.The clinicopathological features and prognosis were compared between the two groups.Time-to-event curves were estimated by the Kaplan-Meier method and compared by two-sided log-rank test.Univariate and multivariate survival analyses were conducted using the Cox risk proportional regression model.ResultsAmong the total 39 patients with HAS,8(20.5%)exhibited normal serum AFP level.Among the rest of the 31(79.5%)patients whose serum AFP levels were elevated,7 had a serum level of AFP above the upper limit of the instrument.In the HAS group,the immunohistochemical positive rates of AFP,CEA and glypican-3 were 71.8%,68.0%and 69.2%,respectively.The level of serum AFP,the rate of vascular invasion and the rate of liver metastasis in patients with HAS were significantly higher than those in patients with common gastric adenocarcinoma(P<0.05).The median survival time of patients with HAS was shorter than that of patients with ordinary gastric adenocarcinoma(17 months vs.48 months),the 1-,3and 5-year survival rates of patients with HAS were 52%,45%and 32%,respectively,while those of patients with common gastric adenocarcinoma were 88%,69%and 41%,respectively.The difference of survival distribution between the two groups was statistically significant(χ2=9.686,P=0.002).Univariate Cox regression analysis revealed that elevated CA125 level,distant metastasis,and radical surgery were associated with prognosis in patients with HAS(P<0.05).Multivariate analysis further revealed that distant metastasis(P=0.034;HR=6.697;95%CI:1.152～38.936)and positive immunohistochemical staining for AFP(P=0.042;HR=4.691;95%CI:1.059～20.777)served as independent risk factors for the survival rate of the patients with HAS.Conclusions1.HAS is a rare special type of gastric cancer.The elevated serum AFP level is an important feature of HAS patients,contributing to confirm its diagnosis.2.Compared with common gastric adenocarcinoma,the clinical symptoms of HAS are not specific,but the prognosis of HAS is poor because of its frequent vascular involvement as well as liver metastases.3.The elevated CA125 level and radical surgery are associated with the prognosis of HAS,and distant metastasis and positive immunohistochemical AFP staining are independent prognostic risk factors for the survival of HAS patients.