Elsevier

Clinical Radiology

Volume 74, Issue 8, August 2019, Pages 653.e1-653.e9
Clinical Radiology

Small hepatocellular carcinoma: using MRI to predict histological grade and Ki-67 expression

https://doi.org/10.1016/j.crad.2019.05.009Get rights and content

Highlights

  • Significant correlation between lesion-to-muscle SI ratio and histological grade of hepatocellular carcinomas.

  • Arterial inhomogeneous enhancement was correlated with high-Ki-67 expression.

  • Pre-operative MRI may serve as a non-invasive tool for prediction of small, aggressive hepatocellular carcinomas.

AIMS

To investigate the predictive indicators of small aggressive hepatocellular carcinomas by examining the association between preoperative magnetic resonance imaging (MRI) parameters and Ki-67 expression and histological grade.

MATERIALS AND METHODS

Sixty patients with small hepatocellular carcinomas (tumour diameter: ≤3 cm, tumour numbers: ≤2) who underwent curative resection or biopsy after contrast-enhanced and diffusion-weighted MRI were evaluated retrospectively. Signal intensity (SI) of the whole lesion and erector spinae muscle was measured quantitatively. Tumour-to-muscle SI ratio was calculated. The association between these MRI parameters and histological grade and Ki-67 level was then investigated.

RESULTS

There was a significant correlation between tumour-to-muscle SI ratio and histological grade in tissues captured during the non-enhanced T1-weighted (p=0.001), arterial phase (p=0.001), and portal venous phase (p=0.036) of dynamic contrast-enhanced MRI and apparent diffusion coefficient (p=0.027). Arterial inhomogeneous enhancement was also correlated with high-Ki-67 expression (p=0.032).

CONCLUSIONS

Preoperative MRI may serve as a non-invasive tool for prediction of small, aggressive hepatocellular carcinomas, which may otherwise be treated conservatively.

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related deaths worldwide.1, 2, 3, 4 Due to the poor prognosis for patients with HCC, it is crucial to identify HCC at an early stage and select the optimal treatment in order to achieve satisfactory outcome. Cirrhosis is the most important clinical risk factor for HCC, and approximately 80% of cases of HCCs develop against a background of cirrhotic liver.5 Studies have showed that human hepatocarcinogenesis involves the stepwise progression of the tumour from a high-grade dysplastic nodule (DN) in a cirrhotic liver to advanced HCC.6, 7, 8 With the optimisation of medical imaging technologies, especially the widely use of magnetic resonance imaging (MRI), the rate of early detection is increasing, especially for small HCC (≤3 cm).

Although small HCCs usually have better outcomes than larger HCCs, a subset of small HCCs have been identified as more aggressive, with poorer clinical prognosis. Investigators have reported that the histological grade of HCCs is a valuable prognostic factor; higher histological grades indicate worse survival probability.9, 10 The nuclear protein, Ki-67, is associated with cell proliferative activity, which may be an indicator of tumour aggressiveness, and is expressed in all phases of the cell cycle except G0, with particularly high expression observed in the G2/M phase.11 High expression of Ki-67 is associated with a higher tumour grade12 and higher mortality.13 Studies have showed that patients with a higher level of Ki-67 expression had a worse prognosis.14, 15 Identification of small HCCs with high histological grade or high Ki-67 expression may help in the selection of appropriate treatment, improving remission rates. The caveat of these prognostic factors is that neither the histological grade nor Ki-67 expression is routinely available through biopsy due to the invasiveness and concern of procedure-related complications. As such, there is a need for non-invasive methods to evaluate Ki-67 expression or histological grade.

Studies have evaluated the correlation between blood supply and histological grade for HCCs,6, 16, 17 some demonstrated that the arterial blood supply decreases as the histological grade progresses in the late stage of HCC development (17). Signal intensity (SI) in dynamic contrast-enhanced MRI was hypothesised to help predict histological grade. Huang et al. reported that apparent diffusion coefficient (ADC) values are significantly negatively correlated with Ki-67 expression,18 but for small HCCs, the correlation between them remains unknown. The purpose of the present study was to investigate the association between histological tumour grade and Ki-67 expression and a battery of preoperative MRI findings, including quantitative and qualitative parameters, for the detection of aggressive small HCCs.

Section snippets

Patient population

The study protocol conformed to the ethical guidelines of the Declaration of Helsinki as reflected in a priori approval by the institutional review board, who waived the requirement for informed consent. Patient medical records were reviewed between January 2011 and December 2017 and 949 patients with histopathologically confirmed HCCs (by surgery or biopsy) were identified. The patients were included consecutively according to the following inclusion criteria1: undergoing routine

Demographic and pathologic characteristics of small HCCs

Baseline demographic and pathological characteristics (Table 1) demonstrated that 10 of the 60 HCCs examined were well-differentiated (WD) HCCs, 43 were moderately differentiated (MD) HCCs, and seven were poorly differentiated (PD) HCCs. Twenty-five of the 60 HCCs had low Ki-67 expression, and the remaining 35 HCCs had high Ki-67 expression. Tumour size (1.93±0.61 cm) ranged from 0.67 to 3 cm in diameter. There were 34 lesions had an AFP value of <20 ng/ml, and the remaining 26 lesions had a

Discussion

This study demonstrated that AFP levels of the selected patients with small HCCs were associated with histological grade, where higher AFP levels were more frequently observed in tumours with higher histological grade, as supported by a previous study.19 Arterial rim enhancement was observed more frequently in the higher histological grade HCCs, especially in MD and PD HCCs. Prior studies have described that arterial rim enhancement can be an indicator for poor differentiation and worse

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements

This study received funding from the Fujian Provincial Health and Family Planning Commission (CN; award number: 2017-CX-27), Fujian Provincial Department of Science and Technology (CN; award number: 2015J0105), and Fujian Medical Elite Cultivation Program (CN; award number: 2015-ZQN-ZD-19).

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    These authors contributed equally to this work and are co-first authors.

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