Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas, gastric fetal type gastrointestinal adenocarcinomas, and hepatocellular carcinomas: An immunohistochemical study with comparison to SALL4, alpha-fetoprotein, glypican-3, and Hep Par1

Zhao, Ming; Sun, Lu; Lai, Jessica C.; Shi, Huaiyin; Mei, Kaiyong; He, Xianglei; Jin, Xiaolong; Lai, Jinping; Cao, Dengfeng

doi:10.1016/j.prp.2018.07.037

Cited by 26 publications

(12 citation statements)

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“…Hence, gastric hepatoid adenocarcinomas seem to resemble hepatocellular carcinomas not only in morphology but also in molecular features. Some investigators reported that SALL4 was useful to distinguish hepatoid adenocarcinomas from hepatocellular carcinomas because no hepatocellular carcinomas showed positive expressions of SALL4 [12,50]. However, others reported hepatocellular carcinomas occasionally showed positive expressions of SALL4 [51,52].…”

Section: Discussionmentioning

confidence: 99%

Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist

et al. 2019

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The Cancer Genome Atlas Research Network classified gastric adenocarcinoma into four molecular subtypes: (1) Epstein-Barr virus-positive (EBV), (2) microsatellite-instable (MSI), (3) chromosomal instable (CIN), and (4) genomically stable (GS). The molecular subtypes of gastric hepatoid adenocarcinomas are still largely unknown. We analyzed 52 hepatoid adenocarcinomas for the expression of surrogate markers of molecular subtypes (MLH1, p53, and EBER in situ hybridization) and some biomarkers (p21, p16, Rb, cyclin D1, cyclin E, β-catenin, Bcl-2, IMP3, ARID1A and HER2), and mutations of TP53, CTNNB1, KRAS, and BRAF. We analyzed 36 solid-type poorly differentiated adenocarcinomas as a control group. Hepatoid adenocarcinomas were categorized as follows: EBV group (EBER-positive), no cases (0%); MSI group (MLH1 loss), three cases (6%); "CIN or GS" (CIN/GS) group (EBER-negative, MLH1 retained), 49 cases (94%). In the CIN/GS group, most of the tumors (59%) had either p53 overexpression or TP53 mutation and a coexisting tubular intestinal-type adenocarcinoma component (90%), suggesting that most hepatoid adenocarcinomas should be categorized as a true CIN group. Hepatoid adenocarcinomas showed relatively frequent expressions of HER2 (score 3+/2+: 21%/19%). Hepatoid adenocarcinomas showed shorter survival, more frequent overexpressions of p16 (67%) and IMP3 (98%) than the control group. None of hepatoid adenocarcinomas had KRAS or CTNNB1 mutations except for one case each, and no hepatoid adenocarcinomas had BRAF mutation. In conclusion, gastric hepatoid adenocarcinomas are a genetically heterogenous group. Most hepatoid adenocarcinomas are "CIN," but a small number of hepatoid adenocarcinomas with MSI do exist. Hepatoid adenocarcinomas are characterized by overexpressions of p16 and IMP3.

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Section: Discussionmentioning

confidence: 99%

Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist

et al. 2019

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“…In addition, SALL4 can also be a diagnostic marker for liver cancer. Evaluation of SALL4 and LIN28, a type of RNA-binding protein, increased the accuracy of distinguishing classic gastric hepatoid carcinomas (GHCs) from HCCs [144]. SALL4 serves as a diagnostic marker of subtyping of HB for the cytology and the prognostication of patients [145].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance

Sun

et al. 2022

IJMS

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SALL4, a member of the SALL family, is an embryonic stem cell regulator involved in self-renewal and pluripotency. Recently, SALL4 overexpression was found in malignant cancers, including lung cancer, hepatocellular carcinoma, breast cancer, gastric cancer, colorectal cancer, osteosarcoma, acute myeloid leukemia, ovarian cancer, and glioma. This review updates recent advances of our knowledge of the biology of SALL4 with a focus on its mechanisms and regulatory functions in tumors and human hematopoiesis. SALL4 overexpression promotes proliferation, development, invasion, and migration in cancers through activation of the Wnt/β-catenin, PI3K/AKT, and Notch signaling pathways; expression of mitochondrial oxidative phosphorylation genes; and inhibition of the expression of the Bcl-2 family, caspase-related proteins, and death receptors. Additionally, SALL4 regulates tumor progression correlated with the immune microenvironment involved in the TNF family and gene expression through epigenetic mechanisms, consequently affecting hematopoiesis. Therefore, SALL4 plays a critical oncogenic role in gene transcription and tumor growth. However, there are still some scientific hypotheses to be tested regarding whether SALL4 is a therapeutic target, such as different tumor microenvironments and drug resistance. Thus, an in-depth understanding and study of the functions and mechanisms of SALL4 in cancer may help develop novel strategies for cancer therapy.

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“…Hepatoid adenocarcinoma of the stomach (HAS), a unique subtype of gastric cancer, is gaining increasing attention in recent years due to its aggressive behaviour, especially the potential for liver metastasis and poor prognosis [1–3]. HAS is characterized by a histological resemblance to hepatocellular carcinoma (HCC); in addition to morphological confirmation, HAS can be confirmed by several immunohistochemical markers, such as AFP, GPC-3, SALL4, and Hap-Par 1 [4, 5]. Previous studies have shown that HAS is the most common of the AFP-producing gastric cancers (GCs), and HAS is commonly believed to have more aggressive biobehaviour and poorer prognosis than cancers without HCC-like morphology [6].…”

Section: Introductionmentioning

confidence: 99%

Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features

Wang

Sun

et al. 2019

Gastric Cancer

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ObjectivesHepatoid adenocarcinoma of the stomach (HAS) is characterized by histological resemblance to hepatocellular carcinoma and a poor prognosis. The aim of this study is to elucidate the clinicopathological and molecular characteristics of HAS.MethodsForty-two patients with HAS who received gastrectomy were enrolled in this study. Based on a panel of 483 cancer-related genes, targeted sequencing of 24 HAS and 22 clinical parameter-matched common gastric cancer (CGC) samples was performed. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analysed with the Kaplan–Meier method.ResultsThe most frequently mutated gene in both HAS and CGC was TP53, with a mutation rate of 30%. Additionally, CEBPA, RPTOR, WISP3, MARK1, and CD3EAP were identified as genes with high-frequency mutations in HAS (10–20%). Copy number gains (CNGs) at 20q11.21-13.12 occurred frequently in HAS, nearly 50% of HAS tumours harboured at least one gene with a CNG at 20q11.21-13.12. This CNG tended to be related to more adverse biobehaviour, including poorer differentiation, greater vascular and nerve invasion, and greater liver metastasis. Pathway enrichment analysis revealed that the HIF-1 signalling pathway and signalling pathways regulating stem cell pluripotency were specifically enriched in HAS. The survival analysis showed that a preoperative serum AFP level ≥ 500 ng/ml was significantly associated with poorer OS (p = 0.007) and tended to be associated with poorer DFS (p = 0.05).ConclusionCNGs at 20q11.21-13.12 happened frequently in HAS and tended to be related to more adverse biobehaviour. The preoperative serum AFP level was a sensitive prognostic biomarker for DFS and OS.Electronic supplementary materialThe online version of this article (10.1007/s10120-019-00965-5) contains supplementary material, which is available to authorized users.

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Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas, gastric fetal type gastrointestinal adenocarcinomas, and hepatocellular carcinomas: An immunohistochemical study with comparison to SALL4, alpha-fetoprotein, glypican-3, and Hep Par1

Cited by 26 publications

References 35 publications

Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist

Gastric hepatoid adenocarcinomas are a genetically heterogenous group; most tumors show chromosomal instability, but MSI tumors do exist

SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance

Hepatoid adenocarcinoma of the stomach: a unique subgroup with distinct clinicopathological and molecular features

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