The effect of cirrhosis on radiogenomic biomarker's ability to predict microvascular invasion and outcome in hepatocellular carcinoma
Authors: Haiyun Tang, Harrison X. Bai, Chang Su, Ashley M. Lee, Li Yang
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. This work was supported by the Natural Science Foundation of China (grant no.: 81301988; to L.Y.) and China Ministry of Education Doctoral Program Spot Founding (grant no.: 20130162120061). TO THE EDITOR: In 2007, Segal et al. found that the 91 genes in the "venous invasion signature" were associated with two predominant imaging traits on computed tomography—the presence of "internal arteries" and the absence of "hypodense halos."1 In 157 hepatocellular carcinoma (HCC) patients who underwent surgical resection or liver transplant, Banerjee et al. showed that these two imaging biomarkers, with the addition of the absence of "tumor liver difference," have high diagnostic accuracy, sensitivity, and specificity in predicting histological microvascular venous invasion (MVI).2 Furthermore, they have high prognostic value in predicting early disease recurrence and poor overall survival.2 We would like to elaborate on some of the findings and raise several concerns. The risk of HCC recurrence depends on the nature of the underlying liver disease. Radiographic venous invasion (RVI)‐negative patients were more likely to have cirrhosis than RVI‐positive patients. It is unclear whether the underlying cirrhosis had any effect on the radiologists' ability to score RVI accurately. Although Banerjee et al. did not perform baseline characteristics analysis between HCC patients who underwent surgical resection versus liver transplant, one key difference between these two groups may be the existence of underlying cirrhosis.3 As demonstrated by the authors, the sensitivity of RVI in predicting MVI was higher in patients who underwent surgical resection than liver transplant (84% vs. 66.7%). This difference in sensitivity suggests that cirrhosis may have affected either the scoring accuracy or underlying tumor biology, making RVI a less‐sensitive predictor of MVI and recurrence/survival. This is clinically relevant given that a positive RVI may affect the patient's liver transplant eligibility. Another interesting finding by Banerjee et al. is that in the subset of 22 patients who underwent preoperative needle‐core biopsy (NCB), identification of MVI through biopsy had a high sensitivity(92.9%) that was similar to RVI, but a much lower specificity (12.5% vs. 87.5% for RVI). In the study cited by Banerjee et al., Pawlik et al. showed that nuclear grade on NCB was a poor predictor of MVI on final pathology.4 However, Pawlik et al. did not attempt to evaluate MVI on any core needle biopsy specimen. Our exhaustive search of the literature did not identify any previous research that compared the diagnosis of MVI through preoperative NCB versus final pathology. In the study by Pawlik et al., patients with a tumor ≤2 cm were more likely to undergo preoperative NCB than those with cirrhosis and a tumor >2 cm.4 This suggests that there are some underlying differences between HCC patients who are selected for biopsy and those who are not. Consequently, there is no definite evidence to prove that RVI is superior to NCB in predicting MVI. In conclusion, there are fundamental differences (e.g., underlying cirrhosis) in HCC patients who were selected for surgical resection versus liver transplant. The accuracy and prognostic value of RVI should be evaluated separately in these two groups.