title: Multiple regression analysis for assessing the growth of small hepatocellular carcinoma: the MIB-1 labeling index is the most effective parameter.
abstract: The aim of this study was to clarify whether histological parameters reflected tumor aggressiveness in patients with hepatocellular carcinoma (HCC). The tumor volume doubling times (TVDTs) of 21 HCCs, less than 3 cm in diameter at the start of the observation period, were calculated in 21 patients in whom the natural progression of the lesion was observed by ultrasonography. Paraffin-embedded sections were prepared from samples obtained by ultrasound-guided fine-needle liver biopsy at the end of the observation period. The histological parameters examined were the MIB-1 labeling index (LI), for which we performed immunohistochemical staining with the MIB-1 monoclonal antibody, using an antigen retrieval method; the nucleo-cytoplasmic (N/C ratio), cellularity, and the nuclear form factor (NFF), were calculated with an imaging analyzer. We performed multiple regression analysis for estimating the growth of small HCCs. With the N/C ratio (0.154 +/- 0.068; mean +/- SD), cellularity (453 +/- 21.8 cells/10(4) microm2), NFF (1.150 +/- 0.096), and degree of HCC differentiation as independent variables, only the MIB-1 LI (11.8 +/- 6.1%) showed a significant correlation with TVDT (207.5 +/- 162.6 days) (r = -0.658; P < 0.05). Compared to the conventional indices of histological atypism tested, i.e., N/C ratio, cellularity NFF, and degree of HCC differentiation, only MIB-1 LI was significantly correlated with small HCC growth rate. The MIB-1 LI may therefore be a simple and useful index of tumor aggressiveness.
authors.affiliation: Department of Internal Medicine, Tsukuba Medical Center, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: M
authors.initials: M
authors.lastname: Doi
authors.forename: T
authors.initials: T
authors.lastname: Sugitani
authors.forename: T
authors.initials: T
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Abei
authors.forename: J
authors.initials: J
authors.lastname: Shoda
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology*; D002467:Cell Nucleus; D003593:Cytoplasm; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D019394:Ki-67 Antigen; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology*; D012044:Regression Analysis; D014463:Ultrasonography
chemical_list: D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D001324:Autoantigens; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009687:Nuclear Proteins