Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Predicts Tumor Differentiation, P-glycoprotein Expression, and Outcome after Resection in Hepatocellular Carcinoma

Abstract

Purpose: To investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for prediction of tumor differentiation, P-glycoprotein (P-gp) expression, and outcome in hepatocellular carcinoma (HCC) patients. Experimental Design: Seventy HCC patients who underwent curative resection were prospectively enrolled in the study. FDG-PET was done 2 weeks preoperatively, and the standardized uptake value (SUV) and the tumor to nontumor SUV ratio (TNR) were calculated from FDG uptake. Tumor differentiation and P-gp expression were examined with H&E and immunohistochemical staining, respectively. Results: SUV and TNR were significantly higher in poorly differentiated HCCs than in welldifferentiated (P = 0.001 and 0.002) and moderately differentiated HCCs (P < 0.0001 and P < 0.0001). The percentage P-gp^positive area was significantly higher in well-differentiated HCCs than in poorly differentiated (P < 0.0001) and moderately differentiated HCCs (P = 0.0001). Inverse correlations were found between SUV and P-gp expression (r = À0.44; P < 0.0001) and between TNR and P-gp expression (r = À0.47; P = 0.01). Forty-three (61.4%) patients had postoperative recurrence. The overall and disease-free survival rates in the highTNR (z2.0) group were significantly lower than in the lowTNR (<2.0) group (P = 0.0001and 0.0002). In multivariate analysis, a high a-fetoprotein level (risk ratio, 5.46; P = 0.003; risk ratio, 8.78; P = 0.006) and high TNR (risk ratio, 1.3; P = 0.03; risk ratio, 1.6; P = 0.02) were independent predictors of postoperative recurrence and overall survival. Conclusions: The results suggest that preoperative FDG-PET reflects tumor differentiation and P-gp expression and may be a good predictor of outcome in HCC.

Prediction of Tumor Recurrence by 18F-FDG PET in Liver Transplantation for Hepatocellular Carcinoma

“…In the Milan or UCSF criteria, size and number of tumors are regarded as representative of the progression and aggressiveness of HCC, with the assumption that more progressive and aggressive HCC is prone to recur by microscopic invasion or seeding. Glucose metabolism as assessed on 18 F-FDG PET is also a factor related to tumor progression or aggressiveness (14)(15)(16)(17)(18). Evident uptake of 18 F-FDG has been observed in poorly differentiated HCC (14)(15)(16)(17), and a correlation between tumor growth rate and 18 F-FDG uptake has also been reported (18).…”

“…Because glucose metabolism assessed on 18 F-FDG PET is related to progression or aggressiveness of HCC (14)(15)(16)(17)(18), it is feasible that 18 F-FDG PET uptake, like size and number of tumors, has prognostic value for tumor recurrence in liver transplantation. However, the appropriate application of 18 F-FDG PET or its significance as a prognostic factor has not been investigated in the prediction of tumor recurrence in liver transplantation for HCC.…”

18F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma

“…Likewise, in HCC, several investigators have reported that 18 F-FDG uptake evaluated by preoperative PET scan is associated with tumor differentiation as well as recurrences and survival after resection or transplantation. [14][15][16][17] Hence, it is feasible that 18 F-FDG uptake on PET scan, like size and number criterion, might be an important prognostic factor in the establishment of treatment and surveillance plans. However, most studies on HCC and 18 F-FDG-PET have focused primarily on either tumor detection in preoperative settings or prognostic value in patients treated with resection or transplantations.…”

“…There are few data on the clinical significance of 18 F-FDG-PET in HCC patients who have undergone nonsurgical treatments. 14,15,[17][18][19] Furthermore, to date, there have been no data on the appropriate application of the clinical significance of 18 F-FDG-PET in patients who have undergone localized CCRT followed by repetitive HAIC for locally advanced HCCs.…”

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“…Positron emission tomography imaging could be a good preoperative tool for estimating the post-LT risk of tumor recurrence because histologic grade and vascular invasion cannot be determined preoperatively. 25,26 Lee and associates demonstrated the clinical impact of 18F-FDG PET/CT in 280 patients who underwent living-donor LT at the National Cancer Center. Of 280 patients, 147 (52.5%) had HCC staged beyond the Milan criteria on the basis of pathologic reports.…”