Hepatoid Adenocarcinoma Of The Stomach Research Articles

Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240ng/ml; 28 out of 31 cases had AFP levels below 25µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

Hepatoid Adenocarcinoma of the Stomach with Liver and Pulmonary Metastases: A Case Report and Literature Review

Hepatoid Adenocarcinoma of the Stomach (HAS) is a rare unique subtype of Gastric Cancer (GC) with a low incidence but a high mortality rate. We report a female case of 67-years-old with APF producing hepatoid adenocarcinoma of the gastric antrum with liver and lung metastases. Abdominal CT of the patient showed multiple liver masses, which were considered as metastatic tumors and proved to be adenocarcinoma by pathological examination of a biopsy. The gastroscopy revealed antral ulcer complicated with bleeding. The biopsy results of hepatoid adenocarcinoma were consistent with the results of liver masses. Moreover, α-Fetoprotein (AFP) increased sharply to 86332 ng/mL. Thus, the diagnosis of gastric hepatoid adenocarcinoma with liver metastasis was established. In terms of treatment, liver TACE embolization was performed first, followed by radical gastrectomy and resection of liver tumor. During the operation, multiple small tumors (less than 5cm in diameter) in the liver were treated by radiofrequency ablation. The patient recovered well after surgery, with a rapid decline in AFP. Postoperative CT indicated the presence of bioactive tumors in the liver and new tumors in the lung. Lung puncture pathology suggests tumor metastasis. Liver and lung were treated with radiofrequency ablation and SOX (Oxaliplatin and Tegacil) chemotherapy. There was no significant recurrence 20 months after surgery, and personalized systematic treatment for this patient was effective. Standard treatment for gastric hepatoid adenocarcinoma has not yet been established, and personalized systematic therapy is the preferred treatment.

Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach.

Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation: A case report and review of literature

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.

Long-term prognostic benefit of adjuvant chemotherapy for patients with hepatoid adenocarcinoma of the stomach after radical resection: A national multicenter study

BackgroundThere is no consensus on whether adjuvant chemotherapy (AC) is effective for hepatoid adenocarcinoma of the stomach (HAS). The aim of this study was to investigate the relationship between AC and the long-term prognosis of patients with HAS. MethodsThe clinicopathological data of 239 patients with primary HAS who underwent radical surgery from April 1, 2004 to December 31, 2019 in 14 centers in China were retrospectively analyzed. Patients were divided into the AC group (127 patients) and the nonadjuvant chemotherapy (NAC) group (112 patients). ResultsKaplan‒Meier (KM) analysis showed that there were no significant differences in the 1-year3-year overall survival rate (OS) and 1-year, 3-year recurrence-free survival rate (RFS) between the AC group and the NAC group (1-year OS: 85.6% vs. 79.8%, 3-year OS: 59.8% vs. 62.4%, 1-year RFS: 69.8% vs. 74.4%, 3-year RFS: 57.2% vs. 55.9%, all P > 0.05). The subpopulation treatment effect pattern plots (STEPP) did not show treatment heterogeneity of AC in patients with HAS. The proportions of local recurrence and metastasis sites in the two groups were similar. Although the smoothed hazard curves of the NAC and AC groups crossed, the peak hazard time was later in the AC group (5.9 and 4.7 months), and the peak hazard rate was lower (0.032 and 0.038, P = 0.987). ConclusionThe current AC regimen may not significantly improve the survival of patients with HAS after radical surgery.

Hepatoid adenocarcinoma of the stomach: CT findings.

To analyze the CT findings of hepatoid adenocarcinoma of the stomach (HAS) and improve the diagnosis accuracy of this condition. The CT images of 22 pathologically confirmed HAS patients were analyzed retrospectively. We investigated the location of lesions, morphology, enhancement features, area of invasion into surrounding organs, lymph node metastasis, and venous tumor thrombus. Among the 22 patients (17 men and 5 women, the mean age was 61.41 ± 9.83 years ranging from 36 to 80 years) with HAS; the morphology of tumors included mass (n = 5), focal ulcer (n = 7), and infiltrating ulcer (n = 10). Extraserous fat was invaded in 12 cases. Enhancement scans showed continuous enhancement in all cases. The CT values of unenhanced scan, the arterial phase, and the portal venous phase are 30.36 ± 6.46, 60.91 ± 17.80, and 75.64 ± 22.09 (HounsfieldUnit, HU), respectively. In six cases, the tumor infiltrated the surrounding organs: liver (n = 1), pancreas (n = 2), and both liver and pancreas (n = 3). In 16 out of 22 patients (72.3%), suspicious lymph node metastasis at CT imaging has then been confirmed by pathological specimens. Intrahepatic metastasis was found in 14 cases. Seven patients had venous tumor thrombus: three patients developed tumor thrombus in the main trunk and intrahepatic branches of the portal vein and two patients in the portal vein, splenic vein, and superior mesenteric vein simultaneously. The CT scans of HAS often show a thickened gastric wall and infiltrating ulceration. Infiltration into extraserosal fat is often seen. Enhancement scans show a continuous and progressive enhancement of lesions. Lymph node metastasis, intrahepatic metastasis, and portal vein tumor thrombus are common in HAS patients.

Hepatoid Adenocarcinoma of the Stomach: A Rare Tumour in an Unusual Subserosal Location

Hepatoid Adenocarcinoma (HAC) is a special type of adenocarcinoma of extrahepatic origin that has overlapping features with Hepatocellular Carcinoma (HCC). Herein, present case is of a 75-year-old man who presented with abdominal pain, bilious vomiting, and constipation for four days, along with a palpable mass in the abdomen for five months. Imaging studies revealed a mass in the subserosal region of the greater curvature of the stomach. Intraoperative findings showed a mass involving the stomach, liver, and omentum, initially suggesting a diagnosis of malignant Gastrointestinal Stromal Tumour (GIST). However, histopathological examination revealed lobules of polygonal cells with abundant eosinophilic to vacuolated cytoplasm and enlarged, moderately pleomorphic nuclei, indicating hepatoid differentiation. The aggressive nature of the lesion, invading the liver and omentum, the absence of risk factors for HCC, negative staining for CD 117 and polyclonal Carcinoembryonic Antigen (pCEA), and positive staining for glypican 3 and CK 19 on immunohistochemistry, confirmed the diagnosis of HAC of the stomach rather than HCC. After surgery, the patient was referred to an Oncology centre. An accurate diagnosis of HAC is crucial due to its aggressive nature and poor prognosis.

Comprehensive Analysis of Genomic Alterations in Hepatoid Adenocarcinoma of the Stomach and Identification of Clinically Actionable Alterations.

Simple SummaryHepatoid adenocarcinoma of the stomach (HAS) is a subset of gastric cancer (GC) histologically characterized by hepatocellular carcinoma-like foci with or without alpha-fetoprotein secretion, which is easily misdiagnosed. Genomic alterations and potential targets for this population are still largely unknown. Additionally, treatment regimens of HAS are mainly based on GC guidelines, which is not reasonable for diseases with great heterogeneity. The present study comprehensively depicts the genomic features of HAS, and they are significantly different from GC, AFP-producing GC (AFPGC), and liver hepatocellular carcinoma (LIHC). Multiple aggressive behavior-related amplificated or deleted regions in HAS are firstly reported. Moreover, reliable and practicable clinically actionable alterations for HAS are identified, providing evidence for making personalized therapy based on the genomic characteristics of HAS instead of GC.Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignancy with aggressive biological behavior. This study aimed to compare the genetic landscape of HAS with liver hepatocellular carcinoma (LIHC), gastric cancer (GC), and AFP-producing GC (AFPGC) and identify clinically actionable alterations. Thirty-eight cases of HAS were collected for whole-exome sequencing. Significantly mutated genes were identified. TP53 was the most frequently mutated gene (66%). Hypoxia, TNF-α/NFκB, mitotic spindle assembly, DNA repair, and p53 signaling pathways mutated frequently. Mutagenesis mechanisms in HAS were associated with spontaneous or enzymatic deamination of 5-methylcytosine to thymine and defective homologous recombination-related DNA damage repair. However, LIHC was characteristic of exposure to aflatoxin and aristolochic acid. The copy number variants (CNVs) in HAS was significantly different compared to LIHC, GC, and AFPGC. Aggressive behavior-related CNVs were identified, including local vascular invasion, advanced stages, and adverse prognosis. In 55.26% of HAS patients there existed at least one clinically actionable alteration, including ERBB2, FGFR1, CDK4, EGFR, MET, and MDM2 amplifications and BRCA1/2 mutations. MDM2 amplification with functional TP53 was detected in 5% of HAS patients, which was proved sensitive to MDM2 inhibitors. A total of 10.53% of HAS patients harbored TMB > 10 muts/Mb. These findings improve our understanding of the genomic features of HAS and provide potential therapeutic targets.

Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.

e16094 Background: Hepatoid adenocarcinoma (HAC) is a rare pathological subtype of extrahepatic tumor, featured by hepatoid differentiation and α-fetoprotein (AFP)-production. Hepatoid adenocarcinoma of the stomach (HAS), accounting for 0.17 to 15% of gastric cancers, is the most common subtype of HAC, and has attracted increasing attention duo to its high degree of malignancy. Compared with classic gastric cancer (GC), HAS showed a higher rate of vascular invasion, lymph node metastasis, and liver metastasis, with only 9% survival at 5 years. In this study, we aim to investigate the molecular features of HAS and identify the potential therapeutic targets for HAS. Methods: We conducted whole-exome sequencing (WES) of 40 paired tumor and normal samples, including 25 HAS, 6 HAC of other organ and 9 AFP-producing gastric cancer (AFPGC). All patients underwent radical surgery at Shanghai Zhongshan Hospital between July 2013 and September 2017. qRT-PCR, Western blot and immunohistochemistry were detected to explore MUC19 expression in HAS. CCK8 assay, Transwell assay, immunofluorescence assay and subcutaneous xenograft tumor model were used to detect functional effects and the mechanism of MUC19. Results: In HAS patients, the top 5 frequently mutated genes were TP53 (44%), TTN (44%), MUC19 (40%), CCNE1 (28%) and CDC27 (28%). Further compared with TCGA datasets, MUC19, CCNE1, CDC27 mutations were almost undetectable in STAD, CRC and HCC. In terms of CNV analysis, VSTM2B, PLEKHF1, POP4, URI1 and TERT were the most frequently amplificated genes in HAS tumor tissues. Interestingly, amplification of 4 genes (VSTM2B, CCNE1, LEKHF1, POP4), which located in chr19q12, was significantly associated with poor prognosis. The tumor mutational burden (TMB) levels and AFP expression of HAS and AFPGC patients were no significantly different, while patients with higher TMB had a remarkably longer overall survival ( p= 0.0065). Moreover, we found MUC19 expression was positively correlated with AFP levels in HAS and MUC19 promoted the transcription of AFP in GC cells. Mechanistically, MUC19 contributed to the aggressive malignancy phenotypes of GC cells through activating the Wnt/β-catenin signaling pathway. Conclusions: MUC19 may be a potential target for HAS diagnosis and treatment. Amplification of genes located in chr19q12 occurred frequently in HAS and were associate with poor prognosis. TMB was sensitive for the overall survival of HAS patients.

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.

Integrative analysis reveals a clinicogenomic landscape associated with liver metastasis and poor prognosis in hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.

Hepatic Metastasis from Hepatoid Adenocarcinoma of the Stomach Mimicking Hepatocellular Carcinoma: Diagnostic Challenge

Hepatoid adenocarcinoma (HAC) is a unique type of extrahepatic adenocarcinoma that histologically mimics the appearance of hepatocellular carcinoma (HCC). Hepatoid adenocarcinoma of the stomach has a poor prognosis with increased potential for liver metastasis. HCC and HAC share clinicopathological and immunohistochemical features. The diagnosis of metastatic hepatoid adenocarcinoma to the liver is challenging. It is often misdiagnosed as hepatocellular carcinoma. The diagnostic dilemma is more

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach

Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Prognostic Analysis of Gastric Signet Ring Cell Carcinoma and Hepatoid Adenocarcinoma of the Stomach: A Propensity Score-Matched Study.

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of primary gastric cancer, and most previous studies have reported that HAS has a poor prognosis due to its aggressive biological behavior. The aim of this study was to compare the prognosis of HAS to that of gastric signet ring cell carcinoma (SRC).MethodsThis was a single-center, retrospective, observational cohort study (January 2010 to January 2016) of gastric cancer patients with pathological HAS and SRC. Overall survival was compared between HAS and SRC patients. We used univariate Cox regression, multivariate Cox regression, propensity score matching (PSM), inverse probability of treatment weighting, standardized mortality ratio weighting, standardized mortality ratio weighting, and overlap weighting to perform a prognostic analysis.ResultsA total of 725 (672 SRC and 53 HAS) patients were included. After nearest-neighbor 1:4 PSM, 200 SRC patients and 50 HAS patients were matched. Only in univariate Cox regression analysis with the cohort before PSM did HAS show a significantly worse prognosis than SRC [hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.02–2.69, p = 0.040]. However, in the analysis of multivariate Cox regression with the cohort before PSM and series analysis based on the propensity score, all of the results indicated that there was no statistically significant difference in overall survival between HAS and SRC (all p > 0.05). Furthermore, in the subgroup of proximal location (p = 0.027), T stage 4a & 4b (p = 0.001), N stage 3a & 3b (p = 0.022), with cancer nodules (p = 0.026), serum CEA higher than the normal value (p = 0.038), and serum CA199 higher than the normal value (p = 0.023), the prognosis of HAS was significantly worse than that of SRC.ConclusionBased on our study, there was no statistically significant difference in overall survival between HAS and gastric SRC patients. However, in patients with an advanced tumor stage, HAS may have a worse overall survival than SRC.

Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.

Hepatoid Adenocarcinoma of the Stomach: Current Perspectives and New Developments.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignant tumor, accounting for only 0.17–15% of gastric cancers. Patients are often diagnosed at an advanced disease stage, and their symptoms are similar to conventional gastric cancer (CGC) without specific clinical manifestation. Morphologically, HAC has identical morphology and immunophenotype compared to hepatocellular carcinoma (HCC). This is considered to be an underestimation in diagnosis due to its rare incidence, and no consensus is reached regarding therapy. HAS generally presents with more aggressive behavior and worse prognosis than CGC. The present review summarizes the current literature and relevant knowledge to elaborate on the epidemic, potential mechanisms, clinical manifestations, diagnosis, management, and prognosis to help clinicians accurately diagnose and treat this malignant tumor.

S2962 Hepatoid Adenocarcinoma - A Rare Malignancy

INTRODUCTION: Hepatoid adenocarcinoma (HAC) is a rare subtype of gastric cancer. It histologically resembles hepatocytes and can produce alpha fetoprotein (AFP). We present a case of HAC with metastasis to the liver, thus mimicking a hepatocellular carcinoma (HCC). Clinical history and immunohistochemical stains are the key to diagnosis. CASE DESCRIPTION/METHODS: We report a 67-year-old male with a history of hypertension who presented to the hospital with epigastric abdominal pain, nausea, and vomiting that was progressively worsening for the past 4 months. Physical exam was remarkable for mild epigastric tenderness with palpation. Laboratory tests showed a hemoglobin of 9.5 gm/dL with iron studies consistent with iron deficiency anemia. The AFP, CA 19-9, and CEA were normal. CT showed extensive mural thickening of the stomach with extensive mediastinal and retroperitoneal lymphadenopathy as well as a hypo-enhancing mass in the left lobe of the liver measuring 3.3 × 3.2 × 2.7 cm. There were no exam, lab, or imaging findings suggestive of chronic liver disease. We performed an upper endoscopy which revealed a large fungating, infiltrative and ulcerated circumferential mass involving the gastric body and fundus. Multiple biopsies were taken which showed fragments of gastric mucosa infiltrated by a poorly differentiated neoplasm. Immunohistochemical stains supported hepatoid differentiation of the neoplasm. Specifically, CK19 and B72.3 stains favored HAC over HCC. Liver biopsy was subsequently performed and showed a similar histologic appearance. Thus, the patient was diagnosed with stage IV HAC with metastasis to the liver. He was followed up by oncology as an outpatient and started on FOLFOX chemotherapy. DISCUSSION: HAC of the stomach with metastasis to the liver can be difficult to diagnose as it can mimic HCC. Our case is even more unusual in that the AFP was normal, although this does not exclude either HAC or HCC. Unfortunately, HAC is an aggressive cancer that carries a poor prognosis. Like in our case, many are diagnosed at an advanced stage and there are no guidelines for the optimal chemotherapy regimen. Since our patient’s AFP levels were normal, he can only be monitored by interval imaging. Fortunately, our patient had excellent baseline functional status, which will hopefully improve his outcomes and tolerance to treatment. With HAC, clinical context and specialized immunohistochemical stains must be considered to make the correct diagnosis and prevent delay in treatment.Figure 1.: Endoscopic picture of Antrum with Mass.Figure 2.: Endoscopic picture of Endoscopy of the body of the stomach.Figure 3.: Endoscopic picture of the Fundus.

Abstract 4746: Genomic alterations and clinical correlations of Chinese hepatoid adenocarcinoma patients

Abstract Background: In recent years, hepatoid adenocarcinoma (HAC), a rare tumor subtype, has attracted more and more attention because of its malignant nature, especially its poor prognosis due to frequent liver metastasis. HAC, recognized as an extrahepatic cancer that resembles hepatocellular carcinoma (HCC), is characterized by the solid sheet-like growth structures of hepatoid differentiation and excessive production of alpha-fetoprotein (AFP). Hepatoid adenocarcinoma of the stomach (HAS) is the most common site of HAC, however, the differences between HAS and HAC of other organs are unknown. Methods: Our Chinese HAC cohort consisted of 31 samples (25 HAS patients and 6 HAC of other organs patients) that were collected in the form of formalin-fixed, paraffin-embedded (FFPE) tumor tissues at Zhongshan Hospital from July 2013 to August 2017 for whole exome sequencing (WES) (OrigiMed, Shanghai). Results: A total of 31 patients with HAC had surgical treatment, 25 patients with HAS (median age 66.5 years, range 48-82) and 6 patients with HAC of other organs (median age 62.5 years, range 52-67). Most HAS patients were male (18/25, 72%), and most HAC of other organs patients were female (4/6, 66.7%). Survival analysis revealed that compared with patients with HAS, patients with HAC of other organs had a significantly poorer overall survival (OS) (p=0.0081) and disease-free survival (DFS) (p=0.0011). The most frequently mutated genes in the HAS tumor samples were TP53 (42%), MUC19 (35%), and TTN (35%). The substitution mutations of CDK4, KRT34 and GOLGA6L3 were only found in HAC from other organs samples but not from HAS samples. Copy number variations (CNVs) of CCNE1, VSTM2B, PLEKHF1 and POP4 were only identified in HAS samples. Interestingly, these 4 genes were located at chr19 and were co-mutated in 5 patients who had a significantly poorer OS than those without these CNVs (11.1 months vs. 19.3 months, respectively, p=0.045). The tumor mutational burden (TMB) of HAS was significantly higher compared with HAC of other organs was also significantly different (4 muts/Mb vs. 1.2 muts/Mb, respectively, p=0.012). Conclusions: Our study revealed the genomic profiling of Chinese HAC patients. Compared to patients with HAS, patients with HAC of other organs had a significantly poorer OS and DFS. The origin for HAC was associated with specific gene mutations and the TMB value. Patients with CNVs in chr19 were significantly associated with a poorer OS. Citation Format: Tianshu Liu, Erbao Chen, Chen Xu, Wei Li, Mengling Liu, Yichou Wei, Yiyi Yu, Yuehong Cui, Qian Li, Shuirong Zhang, Lujia Huang, Yueting Qu. Genomic alterations and clinical correlations of Chinese hepatoid adenocarcinoma patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4746.

The prognosis of hepatoid adenocarcinoma of the stomach: a propensity score-based analysis

BackgroundTo investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery.MethodsWe retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression.ResultsOur data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P = log rank (Mantel-Cox), (before PSM P = 0.397); (1:1 PSM P = 0.345); (1:2 PSM P = 0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching).ConclusionHAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.