title: A technique for automatic/interactive assessment of the proliferating fraction of neoplastic cells in solid tumors. A methodological study on the Ki-67 immunoreactive cells in human mammary carcinomas, including a comparison with the results of conventional S-phase fraction assessments by means of DNA cytometry.
abstract: Based on a computerized microscopy technique, a method has been devised which allows the practising pathologist to easily and rapidly assess quantitatively the relative number of actively proliferating neoplastic parenchymal cells in a tumor nodule. Our method has been tested on a series of 20 conventionally formalin-fixed and paraffin-embedded female mammary adenocarcinomas, using immunoreactivity with the MIB-1 monoclonal antibody against the cell proliferation antigen Ki-67. The values of the proportion of the MIB-1 immunoreactive cell nuclei were compared with those obtained DNA-cytometrically for the fraction of cells in the S-phase; a good correlation was found, although the MIB-1 values were consistently somewhat higher. A prerequisite for a success of the method was, of course, to achieve standardization of the MIB-1 immunostaining technique. By making simple adjustments of it, it could actually be improved to such an extent that almost the same color calibration and thresholding setup could be used. The measuring technique could be either interactive or automatic. The total number of immunoreactive and non-immunoreactive nuclei, as well as the total nuclear area of both cell types were registered in a computerized device. The data were accumulated sequentially for each measure field. To investigate the reproducibility of the immunostaining, two slides of each case were stained on different occasions. Each slide was measured three times; systemically randomly in the x- and y-axis-directions as well as in the subjectively defined histopathologically "most proliferative" area of the tumor. The values obtained were in good agreement with each other and obviously gave some valuable and objective supplementary pieces of information to that of the conventional clinical and histopathologic assessment of the degree of aggressiveness of a malignant neoplasm.
authors.affiliation: Department of Oncology and Pathology, Radiumhemmet, Karolinska Institute, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Parrado
authors.forename: U G
authors.initials: UG
authors.lastname: Falkmer
authors.forename: A
authors.initials: A
authors.lastname: Höög
authors.forename: S
authors.initials: S
authors.lastname: Falkmer
authors.forename: O
authors.initials: O
authors.lastname: Ahrens
authors.forename: F
authors.initials: F
authors.lastname: Rius
authors.forename: L
authors.initials: L
authors.lastname: Grimelius
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002455:Cell Division; D003201:Computers; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D019044:Image Cytometry; D007150:Immunohistochemistry / Q000379:methods*; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D015203:Reproducibility of Results; D016196:S Phase
chemical_list: D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins