title: An improved classification of foci for carcinogenicity testing by statistical descriptors.
abstract: Carcinogenesis is a multi-step process involving genetic alterations and non-genotoxic mechanisms. The in vitro cell transformation assay (CTA) is a promising tool for both genotoxic and non-genotoxic carcinogenesis. CTA relies on the ability of cells (e.g. BALB/c 3T3 mouse embryo fibroblasts) to develop a transformed phenotype after the treatment with suspected carcinogens. The classification of the transformed phenotype is based on coded morphological features, which are scored under a light microscope by trained experts. This procedure is time-consuming and somewhat prone to subjectivity. Herewith we provide a promising approach based on image analysis to support the scoring of malignant foci in BALB/c 3T3 CTA. The image analysis system is a quantitative approach, based on measuring features of malignant foci: dimension, multilayered growth, and invasivity into the surrounding monolayer of non-transformed cells. A logistic regression model was developed to estimate the probability for each focus to be transformed as a function of three statistical image descriptors. The estimated sensitivity of the derived classifier (untransformed against Type III) was 0.9, with an Area Under the Curve (AUC) value equal to 0.90 under the Receiver Operating Characteristics (ROC) curve.
authors.affiliation: Department of Earth and Environmental Sciences, University of Milan Bicocca, Piazza della Scienza, 1, 20126 Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Callegaro
authors.affiliation: Department of Statistics, Computer Science, Applications, University of Florence, Viale Morgagni 59, 50100 Florence, Italy.
authors.forename: Federico Mattia
authors.initials: FM
authors.lastname: Stefanini
authors.affiliation: Center for Environmental Toxicology, Environmental Protection and Health Prevention Agency Emilia-Romagna Region (ER-EPA), Bologna, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colacci
authors.affiliation: Center for Environmental Toxicology, Environmental Protection and Health Prevention Agency Emilia-Romagna Region (ER-EPA), Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Vaccari
authors.affiliation: Department of Earth and Environmental Sciences, University of Milan Bicocca, Piazza della Scienza, 1, 20126 Milan, Italy. Electronic address: chiara.urani@unimib.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Urani
mesh_terms: D000818:Animals; D019540:Area Under Curve; D041702:BALB 3T3 Cells; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic; D007090:Image Interpretation, Computer-Assisted; D016015:Logistic Models; D051379:Mice; D012372:ROC Curve
chemical_list: D002273:Carcinogens
keywords: BALB/c 3T3 cell line; Cell transformation assay; Statistical image descriptors; foci; foci classification