Malignant transformation of hepatocellular adenoma.
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ABSTRACT:
SUBMITTER: Julien C
PROVIDER: S-EPMC8883183 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
Malignant transformation of hepatocellular adenoma.
Julien Céline C Le Bail Brigitte B Chiche Laurence L Balabaud Charles C Bioulac-Sage Paulette P
JHEP reports : innovation in hepatology 20220107 3
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Project description: Not available
| S-EPMC8810563 | biostudies-literature
Project description:IntroductionHepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to hepatocellular carcinoma (HCC), which has emerged to be one of the fastest growing causes of cancer-related mortality globally. This study protocol for a planned systematic review and meta-analysis documents the methodological approach to identify risk factors and their risk estimates for the transformation from HCA to HCC.Methods and analysisTwo independent reviewers will systematically search and extract data from studies in patients of all ages published between January 1970 and June 2021 on PubMed, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus Web of Science, Ovid, The Cochrane Hepatobiliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials by using an a priori defined search strategy. Study quality will be rated with the National Institute of Health quality assessment tools. Disagreements will be resolved by consensus with a third independent reviewer. The primary outcome will be the odds ratio (OR) of developing HCC in patients with prediagnosed HCA depending on the exposure to risk factors. HCC diagnosis must be inferred based on imaging techniques or pathology. We will use R V.4.0.2 to conduct meta-analyses and generate pooled ORs based on random effects models. Results will be presented as forest plots. Cochran's Q and I2 test will be performed to assess heterogeneity between included studies. Funnel plots and Egger's weighted regression will be used to evaluate publication bias.Ethics and disseminationNo ethical approval is required as we will use and analyse data from previously published studies in which informed consent was obtained. The results will be disseminated in a peer-reviewed journal on completion.Prospero registration numberCRD42020206578.
| S-EPMC8354264 | biostudies-literature
Project description:Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the diagnostic category 'carcinoma ex-pleomorphic adenoma' suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.
| S-EPMC8363925 | biostudies-literature
Project description:Malignant transformation (MT) in recurrent parotid pleomorphic adenomas (PAs) is rare; therefore its occurrence lacks reliable predictive factors. Our goal was to clarify the predictors for MT of recurrent parotid PAs based on preoperative clinical parameters. Patients with a clinical diagnosis of recurrent parotid PA were retrospectively enrolled. The association between clinicopathologic variables and MT of PA was assessed using univariate and multivariate analyses. MT occurred in 11.8% of the 467 patients. In univariate analysis, three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, tumors with the largest tumor diameter ≥ 2.4 cm, and abnormal neck lymph node enlargement were associated with MT occurrence. Further, multivariate analysis showed that three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, and abnormal neck lymph node enlargement were independently related to MT. MT of recurrent PA was not uncommon. Clinical signs of malignancy included newly developed facial nerve paralysis, difficulty in mouth opening, three or more previous recurrences, and abnormal neck lymph node enlargement.
| S-EPMC10027859 | biostudies-literature
Project description:BackgroundNephrogenic adenoma (NA) is a rare benign tumor that can develop at any site of the urinary system, with the bladder being the most common, followed by the urethra, ureters, renal pelvises, etc. Currently, it is unclear what the pathogenesis of NA is. This study discussed a rare case of malignant transformation from NA to mesonephric adenocarcinoma of the bladder.Case descriptionA 66-year-old man with a bladder mass was admitted to the hospital. A cystoscopic electro biopsy and transurethral resection of bladder tumor (TUR-BT) pathologically indicated that the patient had an NA of the bladder. Furthermore, immunohistochemistry analysis revealed: Pax-8 (+), Pax-2 (-), CK7 (+), EMA (+), p63 (a small proportion+), Ki-67 (1%+). The patient underwent a robot-assisted laparoscopic partial cystectomy, and the pathology of the resected tumor revealed mesonephric adenocarcinoma of the bladder. Moreover, the immunohistochemistry investigation results showed: AE1/AE3 (+), CK7 (+), CK20 (-), PAX-8 (+), P63 (partial+), GATA-3 (weak+), P53 (a small amount+), and Ki-67 (+, 30% of hot spots). And there were no signs of recurrence found during the 1-year follow-up.ConclusionsIt is rare for NAs of the bladder to develop to mesonephric adenocarcinomas of the bladder, and pathological immunohistochemistry staining is used to make the definitive diagnosis. The high proliferation activity of carcinoembryonic antigen (CEA) (+), P53(+), and Ki-67 are important molecular markers for identifying the malignant transformation of NA, as well as the elevation in the Ki-67 proliferation index.
| S-EPMC11650344 | biostudies-literature
Project description:Pleomorphic adenoma (PA), the most common benign salivary gland tumor, presents unpredictable risks of recurrence and malignant transformation into carcinoma ex pleomorphic adenoma (CXPA), posing significant clinical challenges. To better delineate the tumor progression trajectory, we performed single-cell RNA sequencing on normal salivary glands, primary PA, recurrent PA (rPA), and CXPA, integrating cell trajectory reconstruction, differential gene expression analysis, and key gene network exploration to uncover molecular transitions and intercellular crosstalk underlying PA recurrence and malignant transformation. Our findings revealed GALNT13⁺ myoepithelial cells as CXPA-specific malignant progenitors, marking early malignant conversion, while MIF⁺ myoepithelial cells exhibited enhanced tissue-destructive capabilities. Fibroblasts played dual roles, enforcing fibrotic restraint in primary PA and promoting extracellular matrix degradation in CXPA. The tumor microenvironment demonstrated stage-specific adaptations, with CXPA favoring pro-inflammatory MIF–CD74/CD44 signaling, whereas rPA adopted immunosuppressive characteristics. Together, stromal reprogramming and immune-editing dynamics orchestrated microenvironmental adaptation, linking cellular heterogeneity to clinical aggressiveness. This study presents the first comprehensive molecular atlas of PA progression, highlighting the malignant specialization of myoepithelial subpopulations, fibroblast-mediated stromal remodeling, and immune-driven microenvironmental evolution, offering a valuable framework for precision stratification of malignant potential and future microenvironment-targeted therapeutic strategies.
2025-04-10 | GSE294254 | GEO
Project description:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, predominantly associated with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These infections drive persistent liver inflammation, culminating in cellular dysregulation, fibrosis, and cancer. Despite advancements in targeted therapies, drug resistance and the lack of reliable biomarkers for patient stratification still terribly hinder the treatment of viral HCC. To this end, the review delves into the intricate mechanisms underlying the malignant transformation of viral hepatitis to HCC, including viral integration, genomic instability, epigenetic modifications, oxidative stress, gut microbiota dysbiosis, chronic inflammation, immune escape, and abnormal signaling pathways, highlighting their complex interactions and synergies. Cutting-edge preclinical and clinical advancements in HCC management, including lifestyle modifications, drug therapies, immunotherapies, gene-based approaches, and innovative treatments, are further investigated, with particular priority given to their therapeutic potential and future applications in overcoming current limitations. By synthesizing recent scientific and clinical insights, this review aims to deepen the understanding of HCC pathogenesis in the context of chronic viral hepatitis, paving the way for novel therapeutic targets and personalized treatment strategies, ultimately improving patient outcomes.
| S-EPMC11890166 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a malignant cancer with rapid proliferation and high metastasis ability. To explore the crucial genes that maintain the aggressive behaviors of cancer cells is very important for clinical gene therapy of HCC. LpCat1 was reported to be highly expressed and exert pro-tumorigenic effect in a variety of cancers, including HCC. However, its detailed molecular mechanism remained unclear. In this study, we confirmed that LpCat1 was up-regulated in HCC tissues and cancer cell lines. The overexpressed LpCat1 promoted the proliferation, migration and invasion of HCC cells, and accelerated cell cycle progression, while knocking down LpCat1 significantly inhibited cell proliferation, migration and invasion in vitro and in vivo, and arrested HCC cells at G0/G1 phase. Moreover, we proved for the first time that LpCat1 directly interacted with STAT1 which was generally recognized as a tumor suppressor in HCC. High levels of LpCat1 in HCC could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression. Conversely, down-regulation of LpCat1 would cause the opposite changes to repress the viability and motility of HCC cells. Consequently, we concluded that LpCat1 was a contributor to progression and metastasis of HCC by interacting with STAT1.
| S-EPMC8220817 | biostudies-literature
Project description:Background & aimsMalignant transformation of hepatocellular adenoma (MT-HCA) may occur in up to 5% of tumours. However, the prognostic value of this event remains poorly described. In this study, we aimed to analyse the long-term outcomes of patients undergoing liver resection (LR) for MT-HCA compared to those of patients resected for hepatocellular carcinoma (HCC) occurring on normal liver parenchyma (NP-HCC).MethodsThis single-centre retrospective study included all patients who underwent LR for MT-HCA at Beaujon Hospital between 2001 and 2019. MT-HCAs were classified as small foci of malignant transformation HCA (SF-HCA) and as malignant HCA (M-HCA) in cases of predominant HCC foci. Recurrence-free survival (RFS) of MT-HCA was compared with that of NP-HCC after propensity score matching.ResultsForty patients (24 men, 16 women) underwent LR for MT-HCA, including 23 with SF-HCA and 17 with M-HCA. Of these cases, 16/40 (40%) had β-catenin mutations, 19/40 (47.5%) were inflammatory, 1 was HNF1α-mutated HCA and 4 (10%) were unclassified HCA. Microvascular invasion (12% vs. 0%, p = 0.091) and satellite nodules (25% vs. 4%, p = 0.028) were more frequently observed in M-HCA than in SF-HCA. After a median follow-up of 67 months, 10 (25%) patients with MT-HCA had tumour recurrence, including 9 with M-HCA and 1 with SF-HCA (p = 0.007). M-HCA was linked to significantly poorer 1-, 3-, 5- and 10-year RFS rates than SF-HCA (76%, 63%, 39%, 37% vs. 100%, 100%, 100%, 91%, p = 0.003). Multivariate analysis showed that SF-HCA was independently associated with improved RFS (hazard ratio 0.064; 95% CI 0.008-0.519; p = 0.01). After propensity score matching, NP-HCC was associated with significantly poorer 1-, 3-, 5- and 10-year RFS rates than MT-HCA (p = 0.01).ConclusionsHCA with malignant transformation yields a better long-term prognosis than NP-HCC. Among MT-HCA, SF-HCA is associated with a better prognosis than M-HCA.Lay summaryThe prognostic relevance of malignant transformation of hepatocellular adenoma (HCA) remains unknown. Thus, the aim of our study was to compare the outcomes of patients undergoing liver resection for malignant transformation to those of patients undergoing liver resection for hepatocellular carcinoma (HCC). The main long-term risk after resection for carcinoma is recurrence. In this study, 10/40 patients with malignant transformation of HCA relapsed after resection and we identified age >55 years, presence of satellite nodes, and microvascular invasion as risk factors for long-term recurrence. Compared to patients with HCC, patients who underwent liver resection for HCA with malignant transformation had better long-term survival.
| S-EPMC8326806 | biostudies-literature
Project description:BACKGROUND: Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a thermoablative technique to kill tumor tissue by generating areas of coagulative necrosis. Recent reports have raised concern that RFA may lead to a local recurrence of HCC with an aggressive phenotype and unfavorable prognosis, suggesting that RFA may induce further malignant transformation of HCC. However, the biological effects of RFA on HCC cells have not been directly analyzed. The aim of this study was to determine whether heat stress of the type associated with RFA induces malignant transformation of HCC. METHODS: We assessed the sensitivity of three HCC cell lines (HepG2, Alexander, and Huh7) to heat treatment for 10 min. We then determined the temperature at which a heat-resistant subline can be generated. We established and expanded sublines that survived heat treatment. And their proliferation rates, heat sensitivities, and invasive capacities were further examined. RESULTS: All HepG2 died after 48 degrees C treatment, whereas 49 degrees C treatment was required to kill all Alexander and HuH7. We generated 20 sublines for each parental cell line. A HepG2 subline, HepG2#18, proliferated 100% faster than parental HepG2. Moreover, HepG2#18 survived after 50 degrees C treatment, whereas all parental HepG2 died after heat treatments at 48 degrees C or higher. CONCLUSION: Our results showed that even a single heat treatment could induce further transformation of an HCC cell line. Our results suggest that an insufficient treatment of HCC by RFA that enables survival of some cells might induce further malignant transformation in vivo.
| S-EPMC2716878 | biostudies-other