title: [Standardization and quality control in the evaluation of proliferation parameters in T1T2, N0N1, M0 breast cancer : multicentric retrospective study I. DNA synthesis enzyme activities].
abstract: As part of a clinical research project co-ordinated in Grenoble, six French institutions (CRLCC Angers, CHU Grenoble, Hospices civils Lyon, AP Marseille, CRLCC St-Cloud, CHU Tours) grouped together in order to study the following proliferative parameters in primary breast cancer: DNA synthesis enzymes [thymidine kinase (TK), thymidylate synthase (TS)], signal transduction enzyme [protein tyrosine kinase (PTK)] and S-phase fraction (%S). TK, TS and PTK were measured in cytosols using radio-enzymatic biochemical methods. S-phase was estimated using flow cytometry. The first step consisted in standardization and technical validation of the measurements. The second step consisted in the clinical validation by using a retrospective series of 1,003 breast cancers T1T2, N0N1, M0. We report the results of the first step, together with the distributions of the variables and their relationship with classical clinical variables: 1) Using standardized methods and a cytosolic control, a good reproducibility of measurements was obtained, whether assays were performed in one (TS, PTK) or in several laboratories (TK). 2) Significantly different distributions of TK and TS were observed between the different centres mainly due to different conditions of storage of tumours and cytosols. 3) A highly significant correlation was observed between TK, TS and PTK. Highest TK, TS and PTK levels were observed in tumours with high histological grade or receptor negative tumors. This study clearly illustrates the importance of quality assurance of multicentre studies.
authors.affiliation: Centre René-Huguenin, 35, rue Dailly, 92210 Saint-Cloud.
authors.forename: F
authors.initials: F
authors.lastname: Spyratos
authors.forename: S
authors.initials: S
authors.lastname: Romain
authors.forename: B
authors.initials: B
authors.lastname: Rostaing-Puissant
authors.forename: A
authors.initials: A
authors.lastname: Daver
authors.forename: M
authors.initials: M
authors.lastname: Collona
authors.forename: F
authors.initials: F
authors.lastname: Descotes
authors.forename: P M
authors.initials: PM
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Bougnoux
authors.forename: H
authors.initials: H
authors.lastname: Roth
authors.forename: M
authors.initials: M
authors.lastname: Bolla
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013937:Thymidine Kinase / Q000032:analysis*; D013940:Thymidylate Synthase / Q000032:analysis*
chemical_list: D009363:Neoplasm Proteins; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D011505:Protein-Tyrosine Kinases