CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype

Zhuo, Jianyong; Lu, Di; Tan, Winyen; Zheng, Shusen; Shen, Youqing; Xu, Xiao

doi:10.7150/jca.44697

Cited by 64 publications

(45 citation statements)

References 80 publications

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“…5,8 Our results were concordant with those of previous studies. 9 Of the HCCs, 13.4% expressed CK19 and these were more likely to show higher tumour grade and higher AFP levels at diagnosis. However, CK19 expression was not an independent predictor of OS.…”

Section: Discussionmentioning

confidence: 95%

“…1,2 Immunohistochemical phenotypical aberrancies in HCC have been reported. [3][4][5][6][7][8][9][10] Recently, aberrant expression of intestinal markers such as caudal type homeobox 2 (CDX2) 11,12 and cadherin 17 (CDH17) 13,14 in HCC has been increasingly recognised, albeit rather sparsely. Also, few studies have reported the expression of the novel SATB homeobox 2 (SATB2) (special AT-rich binding protein-2) in HCC, a marker that is considered to be fairly specific to the lower GI tract origin tumours.…”

Section: Introductionmentioning

confidence: 99%

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Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study

et al. 2021

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Aims: Data regarding expression of intestinal markers in hepatocellular carcinoma (HCC) are limited. We determined the clinicopathological associations of cytokeratin (CK)19, a progenitor liver epithelial cell marker as well as biliary epithelial marker, and intestinal immunohistochemical markers expression in HCC and assessed their prognostic value. Methods and results: Tissue sections and/or tissue microarrays (TMAs) from 202 known HCCs were immunostained using CK19, CK20, CDH17, CDX2 and SATB2 antibodies. Haematoxylin and eosin (H&E)-stained slides were reviewed for tumour grading. Clinical and oncological outcomes were retrieved. Associations of staining with clinicopathological features and survival outcomes were evaluated. CK19, CK20, CDH17, CDX2 and SATB2 were positive in 12.8, 5.4, 10.3, 8.6 and 59.9%, respectively. All but SATB2 were strongly associated with higher tumour grade and AFP levels > 400 ng/ml (P < 0.05). CK19positive HCC were more likely to express CDX2 (P = 0.001), CDH17 (P < 0.001) and/or CK20 (P = 0.012). CK20, CDX2 and CDH17 co-expression was seen in five cases (2.5%). CK19 and SATB2 positivity, tumour size ≥ 5 cm, background cirrhosis, AFP > 400 ng/ml and having no treatment were associated with decreased overall survival by log-rank test and univariable proportional hazards regression. However, in a multivariable model, CK19 and SATB2 positivity were not independent predictors of decreased survival while their association with known poor prognosticators in HCC was evident. Conclusions: HCC can express markers of intestinal differentiation. This phenotypical aberrancy correlates with variable clinicopathological parameters, some of which are independent predictors of poor survival.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study

et al. 2021

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“…CK19 is regarded as a progenitor marker of HCC ( 19 ). CK19-positive HCC is a characteristic subtype as it exhibits distinctive molecular profiling ( 20 ). Therefore, we assessed the consistency of CK19 expression between F0 and F1.…”

Section: Resultsmentioning

confidence: 99%

Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts

Zhuo

Wang

et al. 2021

Chinese Journal of Cancer Research

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Objective Patient-derived xenograft (PDX) models provide a promising preclinical platform for hepatocellular carcinoma (HCC). However, the molecular features associated with successful engraftment of PDX models have not been revealed. Methods HCC tumor samples from 76 patients were implanted in immunodeficient mice. The molecular expression was evaluated by immunohistochemistry. Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test. The independent prediction parameters were identified by logistic regression analyses. Results The engraftment rate for PDX models from patients with HCC was 39.47% (30/76). Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates. Tumors with poor differentiation and vascular invasion were related to engraftment success. The positive expression of CK19, CD133, glypican-3 (GPC3), and Ki67 in tumor samples was associated with engraftment success. Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment. Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates, with 71.9% in GPC3 + /Ki67 + tumors, 30.8% in GPC3 − /Ki67 + tumors, 15.0% in GPC3 + /Ki67 − tumors, and 0 in GPC3 − /Ki67 − tumors. Conclusions Successful engraftment of HCC PDXs was significantly related to molecular features. Tumors with the GPC3 + /Ki67 + phenotype were the most likely to successfully establish HCC PDXs.

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“…5,6 Compared with CK19negative HCCs, CK19-positive HCCs exhibit highly aggressive behavior, which is associated with poorer prognosis and a higher rate of recurrence. 6,7 Expression of CK19 is an important independent prognostic predictor of HCC. 8 Preoperative prediction of CK19 expression is of great significance for prognostic evaluation and formulation of treatment strategies for patients with HCCs.…”

Section: Introductionmentioning

confidence: 99%

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

Chen¹,

Chen²,

Lin³

et al. 2021

JHC

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Cytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). Patients and Methods: A total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrencefree survival (RFS) was also analyzed by incorporating the CK19 expression and other factors. Results: For predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732-0.907, P<0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753-0.912, P<0.001) and the sensitivity was 0.960. Intratumoral hemorrhage and peritumoral hypointensity on HBP were independent risk factors for HCC recurrence by multivariate analysis. Based on predicted CK19 expression and the independent risk factors, a nomogram was developed to predict RFS and achieved C-index of 0.707. Conclusion:This study successfully established and verified an optimal DLR model for preoperative prediction of CK19-positive HCCs based on gadoxetic acid-enhanced MRI. The prediction of CK19 expression in HCC using a non-invasive method can help inform preoperative planning.

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CK19-positive Hepatocellular Carcinoma is a Characteristic Subtype

Cited by 64 publications

References 80 publications

Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study

Aberrant expression of SATB2, CDX2, CDH17 and CK20 in hepatocellular carcinoma: a pathological, clinical and outcome study

Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts

Preoperative Prediction of Cytokeratin 19 Expression for Hepatocellular Carcinoma with Deep Learning Radiomics Based on Gadoxetic Acid-Enhanced Magnetic Resonance Imaging

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