Hepatoid Adenocarcinoma Of Stomach Research Articles

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases.

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.

Analysis of enhanced CT imaging signs and clinicopathological prognostic factors in hepatoid adenocarcinoma of stomach patients with radical surgery: a retrospective study

BackgroundTo investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS).MethodsForty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan–Meier method.Results24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14–103.66), 6.83 (95%CI, 1.08–43.08) and 42.67 (95%CI, 3.66–496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825–0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001).ConclusionsPreoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.

Prognostic significance of preoperative serum tumor markers in hepatoid adenocarcinoma of stomach (HAS)

BackgroundThe role of preoperative serum tumor markers in HAS patients was vague, we designed the study to explore the effect of preoperative serum tumor markers on predicting the prognosis of HAS patients.MethodsA total of 139 patients were included according to the different tumor makers. X-tile tool was employed to identify the optimal cut-off values of respective tumor makers. Multivariate analyses were conducted to determine independent risk factors.ResultsThe optimal cut-off value of alpha-fetoprotein (AFP) for 3-years overall survival (OS) and recurrence-free survival (RFS) was 516 ng/mL. Patients with high-level AFP values assumed significantly worse OS and RFS than those with low-level AFP values (P = 0.028 and P = 0.011, respectively). The optimal cut-off value of Carbohydrate antigen (CA)19–9 for OS and RFS was 51.3 U/mL. And the survival results were similar with AFP in the aspects of OS and RFS (P = 0.009 and P < 0.001, respectively). Multivariate analyses showed that high serum AFP was an independent risk factor for OS and RFS of HAS patients (HR7.264; 95% CI 1.328–39.738; P = 0.022 and HR 2.688; 95% CI 0.922–7.836; P = 0.070, respectively). CA19–9 could perform as a fair substitute to predict the HAS patients’ OS and RFS when the preoperative serum AFP was unavailable (HR 7.816; 95% CI 2.084–29.308; P = 0.002 and HR 4.386; 95% CI 1.824–10.547; P = 0.001, respectively). Other tumor markers didn’t present significant influences.ConclusionsApplying preoperative serum AFP level to predict the HAS patients’ prognosis is feasible and preoperative serum high-AFP is an independent risk factor for OS and RFS of HAS patients. Preoperative serum CA19–9 could be an alternative choice when AFP was absent.

Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach

Hepatoid adenocarcinoma of the stomach (HAS) is a particular subtype of Gastric cancer (GC) with distinct pathological characteristics and genetic profile, but most HAS patients were received identical regimens as common GC. To date, only a few studies has been conducted to investigate the molecular characteristics of HAS, which may prevent the rational application of new anticancer strategies. To further obtain the genetic features and potential predictive and prognostic biomarkers of HAS, our current study evaluated the clinical implications of spectrum molecular markers in 36 surgical resection specimens. None Epstein-Barr virus (EBV) positive and/or micro-satellite instable high (MSI-h) tumors occurred in our study implies that the molecular classification of HAS should be mainly categorized into genomic stable (GS) and chromosomal instability (CIN) phenotypes, and wild type P53 status predicts better prognosis. More importantly, although the prognosis and clinical characteristics were independent of programmed cell death-ligand 1 (PD-L1), the presence of tumor infiltrating lymphocytes (TILs) still suggested that a portion of the enrolled HAS patients are potentially appropriate candidates for immune checkpoint blockade therapy. Additionally, the immune prognostic index (IPI) and derived neutrophil to lymphocyte ratio (dNLR) demonstrated their potential as reliable and economic indicators for predicting prognosis of HAS. We hope this first systematic evaluation will help in deciphering the molecular characterization and potential individualized regimens for this particular subtype of GC.

Effect of Immune Checkpoint Inhibitors Plus Chemotherapy on Advanced Gastric Cancer Patients with Elevated Serum AFP or Hepatoid Adenocarcinoma.

PurposeAlpha-fetoprotein-producing gastric cancer (AFPGC) and hepatoid adenocarcinoma of stomach (HAS) are rare types of gastric cancer, with specific clinical manifestations and poor prognosis. The standardized treatment process of such cancers remains elusive. We aim to investigate the efficacy of immunotherapy combined with chemotherapy on patients with AFPGC or HAS.Patients and MethodsAFPGC and HAS patients who underwent immunotherapy and/or chemotherapy as the first-line treatment at our institute from June 2016 to December 2018 were enrolled in this observational study. Their clinicopathological characteristics, serum AFP level and treatment methods were collected. The progression-free survival (PFS) and overall survival (OS) were analyzed and compared between patients who received immunotherapy plus chemotherapy and those received chemotherapy.ResultsA total of 21 patients with advanced AFPGC or HAS were included in the study and the median follow-up time was 28.0 months. Of the 21 patients, 7 patients received immunotherapy of PD-1 antibody (nivolumab) plus chemotherapy and 14 patients as control received chemotherapy with or without Herceptin/Apatinib. The median progression-free survival (mPFS) time was 5.0 months (4.3 months in the control group and 22.0 months in the immunotherapy group). The median overall survival (mOS) time of the control group was 16.0 months (14.0 months in chemotherapy alone subgroup, 20.0 months in chemotherapy plus Apatinib or Herceptin subgroup), while the mOS of patients receiving immunotherapy was not reached.ConclusionThis study suggested PD-1 checkpoint inhibitor plus chemotherapy could benefit AFPGC and HAS patients. Its mechanism of action warrants further investigation.

Genomic alterations and clinical correlations of Chinese patients with hepatoid adenocarcinoma of the stomach/alpha-fetoprotein gastric cancer.

e13514 Background: Hepatoid adenocarcinoma of stomach (HAS) is a rare subtype of gastric cancer (GC) with poor prognosis due to frequent liver metastasis. HAS, recognized as an extrahepatic cancer that resembles hepatocellular carcinoma (HCC), is characterized by solid sheet-like growth structures with hepatoid differentiation and excessive production of alpha-fetoprotein (AFP). This HAS subtype of GC (AFPGC) is genetically distinct compared to other common GC but requires more evidences for better characterization. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were collected from 25 HAS and 9 AFPGC patients at Zhongshan Hospital from July 2013 to August 2017 for whole exome sequencing (WES) test. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: Our cohort included 25 males and 9 females who had undergone surgical treatment. The 25 HAS patients had a median age of 66.5 years (range 48-82) and the 9 AFPGC patients had a median age of 64 years (range 52-76). Patients with AFP&gt;20 had a significantly better overall survival (OS) compared with patients with AFP≤20. The most frequently mutated genes were TP53 (44%), TTN (44%), and MUC19 (30%) in HAS tumor samples and CDC27 (44%), NKX2-3 (44%), and TTN (44%) in AFPGC samples. Patients with URI1 or POP4 alterations had a significantly poorer OS than patients without those genes mutations (7.6 months vs. 19.8 months, p = 0.016, and 10.9 months vs. 19.7 months, p = 0.038, respectively). However, patients with SPTA1 alterations had a significantly better OS compared to patients without SPTA1 alterations (27.6 months vs. 15.8 months, p = 0.042). Patients with higher tumor mutational burden (TMB) (≥3.9 muts/Mb) had a significantly better OS compared with patients with lower TMB (&lt;3.9 muts/Mb), which indicated TMB may be an independent prognostic factor (HR: 0.032, 95%CI: 0.003-0.33, p = 0.004). Conclusions: Our study revealed the genomic profile of HAS/AFPGC patients. The most frequently mutated genes in HAS and AFPGC were different, which helps to better characterize these tumors. AFP and TMB may be potential biomarkers for predicting patients’ prognosis.

An analysis of clinicopathological characteristics and prognosis on hepatoid adenocarcinoma of stomach.

e16558 Background: Hepatoid adenocarcinoma of the stomach(HAS) is a rare type of gastric adenocarcinoma(GAC). At present, histopathology is the gold standard for the diagnosis of HAS, however, HAS is easy to be missed diagnosis, and lack of a perfect diagnosis system and effective treatment strategy. In this research, clinical pathological features will be analyzed to improve the diagnostic system, judge prognosis and provide clues for exploration of pathogenesis and targeted therapy of HAS. Methods: 576 cases including 5 confirmed patients with HAS were enrolled onto this study from 1320 patients with GAC. 10 cases of HAS were diagnosed by the second histopathological examination from the other 571 enrolled cases. 30 cases from the remaining 561 enrolled patients were randomly selected as the control group. The information of the two group cases were completed by collecting the existing case data, detecting the missed immunohistochemical indicators and telephone follow-up. The clinicopathological features of the two group cases were compared, and the treatment and prognosis of 15 HAS cases were analyzed. Results: In this study, 15 cases of HAS were found in 576 patients with GAC, including 5 cases from the 1st pathological diagnosis and 10 cases from the 2nd pathological diagnosis. There was no significant difference in age, gender, HP positive rate, serum CEA or CA19-9 level, tumor size, TNM stage, tumor invasion depth, lymph node invasion, distant metastasis rate, differentiation degree, nerve/vascular invasion, and Ki-67 expression level between the two groups( P&gt; 0.05). Compared with the control group, the serum AFP level, and the expression level of GPC3, AFP, EGFR and VEGF protein of patients in HAS group were significantly high, as well as the patients in the HAS group were more likely to develop liver metastasis( P&lt; 0.05). The mOS was 12 mo vs 42 mo for HAS group vs control group( P&lt; 0.05). Multivariate analysis showed immunohistochemical AFP staining intensity was an independent risk factor for prognosis of HAS. Conclusions: As a special type of GAC, HAS is prone to developing liver metastasis with poor prognosis. Based on the higher missed diagnosis rate of HAS, it is suggested to make 2nd cancer histopathological diagnosis including immunohistochemical detection of AFP and GPC3 for GAC patients with significantly increased serum AFP level. The intensity of immunohistochemical AFP staining is an independent risk factor for the prognosis of patients with HAS. VEGF, EGFR and PD-1 / PDL-1 may be potential therapeutic targets of HAS, which is worth further study.

Hepatoid Adenocarcinoma of Stomach: Emphasis on the Clinical Relationship with Alpha-Fetoprotein-Positive Gastric Cancer.

Aims Both hepatoid adenocarcinoma of stomach (HAS) and alpha-fetoprotein-positive gastric cancer (AFPGC) are rare but aggressive subtypes of gastric cancer, but few studies focus on the clinicopathologic differences and prognostic factors between them because of their rarity and histologic overlap. And the significance of AFP level in HAS prognosis was not well studied. Methods 41 patients with AFPGC and 52 patients with HAS were included in this study. The clinicopathologic features were compared by Chi-square analysis. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed with the Kaplan-Meier method. Results The patients with HAS were of a younger age compared with AFPGC, and nearly 60% of tumor located in the gastric antrum and the gastric fundus of cardia. The OS of AFPGC was shorter than that of HAS, due to a higher rate of metastasis. Furthermore, the survival analysis showed that HAS with high AFP expression (AFPHigh HAS) had a significantly poorer OS compared to HAS with low AFP expression (AFPLow HAS) (P=0.046). Conclusions Compared with AFPGC, the patients of HAS were of a younger age and had less rate of liver and other organ metastasis. The serum AFP level was a sensitive prognostic indicator for OS. Therefore, much attention should be paid to AFPHigh HAS in clinical practice.

Clinicopathological characteristics and prognostic factors of hepatoid adenocarcinoma of stomach

Hepatoid adenocarcinoma of the stomach (HAS) , a rare and specific type of primary gastric adenocarcinoma, is a highly malignant neoplasm characterized by a poor prognosis and a histological component that mimicks hepatocellular carcinoma morphologically as well as immunophenotypically. In the literature, only liver and lymph nodes metastases have been identified as determinants for survival in patients with HAS. Key words: Stomach neoplasms; alpha-fetoproteins; Immunohistochemistry; Prognosis

Hepatoid Adenocarcinoma of the Stomach with Liver Metastasis

A hepatoid adenocarcinoma of stomach, a subtype of gastric cancr, is characterized by a histologic resemblance to a hepatocellular carcinoma and -feto protein production. Another feature is early metastasis to the liver and lymph nodes, thus revealing a poor prognosis. We report a case of a hepatoid adenocarcinoma of the stomach with liver metastasis. A 52-year-old male visited our hospital with a chief complaint of indigestion. Gastroscopic examination showed a Borrmann type-II lesion on the lesser curvature of the antrum. The CT scan showed a suspected advanced gastric cancer with liver metastasis. The serum AFP level was 123 ng/ml. A radical subtotal gastrectomy and a right hemihepatectomy were performed simultaneously. Pathologic examination confirmed the lesion to be confined to the submucosa. The gastric lesion was a hepatoid adenocarcinoma, and the hepatic lesion was a metastatic adenocarcinoma from the stomach. Therefore, he was classified as having stage IV (T1N1M1) gastric cancer. In cases of a hepatoid adenocarcinoma of the stomach, even patients with early gastric cancer can be staged into the poor prognostic group.