Flow cytometric analysis of DNA ploidy in hepatocellular carcinoma

Abstract

To examine the prognostic and pathobiologic significance of DNA content, the authors studied the surgically resected hepatocellular carcinomas of 69 patients by flow cytometric analysis. Homogeneity of DNA content within individual tumor nodules was present in 15 (88%) of 17 specimens examined. Similarly, homogeneity of DNA content in tumors having multiple nodules was found in 8 (73%) of 11 specimens. In 64 tumors with homogeneous DNA content evaluated further, DNA aneuploidy was present in 30 (46.9%) specimens, and the proportion of aneuploid tumors was similar in the large (> 5 cm in diameter, n = 35) and small (≤ 5 cm, n = 25) lesions, at 42.9% and 40%, respectively. Overall, the diploid tumors had serum α-fetoprotein levels increased to greater than 500 μg/mL more frequently than did the aneuploid tumors (P = .037). DNA content did not correlate significantly with hepatitis B surface antigen, presence of liver cirrhosis, cellular differentiation, tumor size, or tumor encapsulation. DNA content also did not influence tumor invasiveness in terms of liver invasion, presence of tumor microsatellites, or venous permeation. With multivariate Cox regression analysis, tumor encapsulation (P = .015), negative resection margin (P = .007), and DNA ploidy pattern stratified according to large and small tumors (P = .024) were favorable prognostic factors. In the small tumors, a diploid DNA pattern was associated with significantly better patient survival than was an aneuploid pattern (P = .012). In the large tumors, on the contrary, a diploid pattern was associated with poorer patient survival than was an aneuploid pattern (P = .029). The authors conclude that DNA ploidy pattern in hepatocellular carcinomas is homogeneous and stable. It supplements other predictors in prognostication when the lesions are stratified into small and large ones by tumor size. It is of particular importance as a predictor because it can be assessed preoperatively in needle-biopsy specimens.