Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior

Lu, Xinyuan; Xi, Tao; Lau, W. Y.; Dong, Hui; Zhu, Zhen; Shen, Feng; Wu, Mengchao; Wang, Cong

doi:10.1245/s10434-011-1585-7

Cited by 55 publications

(52 citation statements)

References 24 publications

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“…These findings are consistent with observations reported by other studies (7,18,(28)(29)(30). A correlation between K19 expression and high AFP levels and high-grade HCC has been demonstrated by Yuan et al (29).…”

Section: Discussionsupporting

confidence: 93%

“…This study has demonstrated that K19 and K7 expression were observed in 11 and 24% of our 79 patients with HCC, respectively. This expression proportion was similar to earlier studies reporting K19 or K7 in 10-50% of HCCs, despite geographic differences, different carcinogens and genetic backgrounds (5)(6)(7)9,(27)(28)(29). In this study, we found that the K19 and K7 positivity rate was highest in small HCCs and decreased in advanced large HCCs.…”

Section: Discussionsupporting

confidence: 92%

“…Since K19 expression was associated with high tumor grade and high AFP levels in this study, the results of K19 as a prognostic factor for HCC is reasonable. The prognosis of patients with K19-positive HCC is considered to be worse than those with pure HCC (9,21,28). In this study, K19 expression in HCC was not an independent predictor of the overall rate of survival in all patients with HCC.…”

Section: Discussioncontrasting

confidence: 50%

“…A correlation between K19 expression and high AFP levels and high-grade HCC has been demonstrated by Yuan et al (29). Similarly, serum AFP concentration in patients with K19-positive HCC increases along with K19 immunostaining grades, suggesting a correlation between serum AFP and K19 expression (28). Uenishi et al also demonstrated that K19 expression correlates with poor differentiation of HCC (31).…”

Section: Discussionmentioning

confidence: 81%

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Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma

et al. 2012

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors characterized by a multistep process of tumor development. Nodular lesions that differ from the surrounding liver parenchyma and are characterized by cytological or structural atypia are termed dysplastic nodules (DNs). DNs are well-known precancerous HCC lesions. Expression of keratin (K) 19 and K7, molecular markers of hepatic progenitor cells and cholangiocytes, has been reported in certain HCCs. However, it remains unclear whether K19-positive HCC cells are derived from true hepatic progenitor cells or mature cells that have undergone a dedifferentiation or a transdifferentiation process. In total, 107 tissue sections (13 low-grade DNs, 15 high-grade DNs, 27 small HCCs and 52 large HCCs) from resected liver samples and 132 HCC tissue microarray (TMA) cores were subjected to immunohistochemical analysis for K19 and K7. Clinicopathological data of the HCC patients were evaluated. K19 expression was found in 0% of DNs, 19% of small HCCs (≤2 cm), 8% of large HCCs (>2 cm) and 8% of TMA samples. K7 expression was found in 14% of DNs, 41% of small HCCs, 15% of large HCCs and 6% of TMA samples. Among the five K19-positive small HCCs, four were distinctly nodular and one tumor was an infiltrative type. No vaguely nodular HCC was positive for K19. K19 expression was significantly associated with histological grade (P=0.023), serum α-fetoprotein level (P=0.001) and K7 expression (P=0.001) in HCC. K19 expression was an independent prognostic factor for overall survival in non-viral HCC patients (P=0.003). K19 expression is extremely rare in DNs and occurs in progressed small HCCs. Our results suggest that K19 expression may be an acquired feature of carcinoma cells during HCC progression in certain HCCs.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 81%

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Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma

et al. 2012

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“…The mechanism of tumour progression is unclear and more experience is needed regarding the type of primary or secondary tumour (33,34), tumour size in the liver parenchyma, interval between the PVE and administration of HSC and subsequent liver resection and other factors, mostly laboratory parameters to determine the risk of tumour progression following the PVE with administration of HSC. A compensatory increased arterial blood fl ow to the liver following the PVE, known as "hepatic arterial buffer response", which may paradoxically cause a higher blood supply of the tumour foci in the liver, will probably play a role (35,36,37,38).…”

Section: Discussionmentioning

confidence: 99%

Portal vein embolization and application of autologous stem cells in patients with primary unresectable liver tumours

Třeška¹,

Koza²,

Lysák³

et al. 2013

BLL

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Abstract:Background: Only 15-20 % of patients with liver tumours can undergo radical surgery. Insuffi cient future liver remnant volume (FLRV) is one of the main causes of tumours unresectability. Portal vein embolization (PVE) together with administration of haematopoietic stem cells (HSC) may expand the operability of primary unresectable liver tumours. Methods: In this pilot study, the authors reported on fi ve patients (1 hepatocellular carcinoma, 4 colorectal cancer metastases) with FLRV <30 %, who underwent PVE on the side of the tumour with a subsequent application of HSC to the non-embolized branch of portal vein. Results: PVE with HSC application was without any complications. In three patients, a suffi cient increase of FLRV occurred within 2-4 weeks followed by a liver resection. All patients were between 5-12 months after the surgery in good condition; one of them was diagnosed with pulmonary metastasis after nine months that was successfully treated with laser metastasectomy. In one patient with hepatocellular carcinoma, an increase of FLRV and progression of the tumour in the liver occurred following the PVE with administration of HSC and the patient was treated only symptomatically. Despite an adequate increase of FLRV, severe intraabdominal adhesions hampered liver resection in one patient. Conclusions: Combination of PVE with HSC administration appeared to be a promising method that stimulated growth of FLRV with a subsequent possibility of an early radical liver resection. The issue is a danger of tumour progression in the liver parenchyma following the PVE with HSC. The current randomized study should answer these questions (Tab. 1, Fig. 4, Ref. 38). Full Text in PDF www.elis.sk.

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Preoperative Diagnosis of Dual‐Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models

Zhang

et al. 2022

Magnetic Resonance Imaging

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Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC). Purpose: To develop and validate clinical and radiomics models based on contrast-enhanced MRI for the preoperative diagnosis of DPHCC. Study type: Retrospective. Population: A total of 87 patients with DPHCC and 92 patients with non-DPHCC randomly divided into a training cohort (n = 125: 64 non-DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non-DPHCC; 26 DPHCC). Field Strength/Sequence: A 3.0 T; dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging sequence. Assessment: In the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]) and their discriminatory efficacy assessed and compared.Statistical Tests: The independent sample t test, Mann-Whitney U test, Chi-square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant. Results: In the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831-0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779-0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526-0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543). Conclusion: MRI radiomics models may be useful for discriminating DPHCC from non-DPHCC before surgery.

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Hepatocellular Carcinoma Expressing Cholangiocyte Phenotype Is a Novel Subtype with Highly Aggressive Behavior

Cited by 55 publications

References 24 publications

Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma

Expression of K19 and K7 in dysplastic nodules and hepatocellular carcinoma

Portal vein embolization and application of autologous stem cells in patients with primary unresectable liver tumours

Preoperative Diagnosis of Dual‐Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models

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