title: Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma.
abstract: Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan. miwa@med.kurume-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Fujioka
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: O
authors.initials: O
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Kojiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011169:Portal Vein / Q000473:pathology; D011498:Protein Precursors / Q000378:metabolism*; D011516:Prothrombin / Q000378:metabolism*; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin