title: Prediction of BRCA1 germ-line mutation status in patients with breast cancer using histoprognosis grade, MS110, Lys27H3, vimentin, and KI67.
abstract: Family structure, lack of reliable information, cost, and delay are usual concerns when deciding to perform BRCA analyses. Testing breast cancer tissues with four antibodies (MS110, lys27H3, vimentin, and KI67) in addition to grade evaluation enabled us to rapidly select patients for genetic testing identification. We constituted an initial breast cancer tissue microarray, considered as a learning set, comprising 27 BRCA1 and 81 sporadic tumors. A second independent validation set of 28 BRCA1 tumors was matched to 28 sporadic tumors using the same original conditions. We investigated morphological parameters and 21 markers by immunohistochemistry. A logistic regression model was used to select the minimal number of markers providing the best model to predict BRCA1 status. The model was applied to the validation set to estimate specificity and sensibility. In the initial set, univariate analyses identified 11 markers significantly associated with BRCA1 status. Then, the best multivariate model comprised only grade 3, MS110, Lys27H3, vimentin, and KI67. When applied to the validation set, BRCA1 tumors were correctly classified with a sensitivity of 83% and a specificity of 81%. The performance of this model was superior when compared to other profiles. This study offers a new rapid and cost-effective method for the prescreening of patients at high risk of being BRCA1 mutation carriers, to guide genetic testing, and finally to provide appropriate preventive measures, advice, and treatments including targeted therapy to patients and their families.
authors.affiliation: Department of Cancer Genetics/CIC-P Inserm 9502, Paoli Calmettes Institute, University of Aix-Marseille II, Marseille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hassanein
authors.forename: Laetitia
authors.initials: L
authors.lastname: Huiart
authors.forename: Violaine
authors.initials: V
authors.lastname: Bourdon
authors.forename: Laetitia
authors.initials: L
authors.lastname: Rabayrol
authors.forename: Jeanine
authors.initials: J
authors.lastname: Geneix
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.forename: Paule
authors.initials: P
authors.lastname: Meynard
authors.forename: Helene
authors.initials: H
authors.lastname: Dreyfus
authors.forename: Dominique
authors.initials: D
authors.lastname: Petrot
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Noguchi
authors.forename: François
authors.initials: F
authors.lastname: Eisinger
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Extra
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
mesh_terms: D019313:BRCA1 Protein / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006657:Histones / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D016015:Logistic Models; D008239:Lysine; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D018579:Patient Selection; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D046888:Tissue Array Analysis; D014746:Vimentin / Q000032:analysis*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D006657:Histones; D019394:Ki-67 Antigen; D014746:Vimentin; D008239:Lysine