Standardization and quality control in the evaluation of proliferation parameters in T1T2, N0N1, M0 breast cancer: multicentric retrospective study 1. DNA synthesis enzyme activities

As part of a clinical research project co-ordinated in Grenoble, six French institutions (CRLCC Angers, CHU Grenoble, Hospices civils Lyon, AP Marseil le, CRLCC St-Cloud CHU Tours) grouped together in order to study the follow ing proliferative parameters in primary breast cancer.. DNA synthesis enzym es [thymidine kinase (TK), thymidylate synthase (TS)] signal transduction e nzyme [protein tyrosine kinase (PTK)] and S-phase fraction (%S). TK, TS and PTK were measured in cytosols wing radio-enzymatic biochemical methods. S- phase was estimated using flow cytometry. The first step consisted in stand ardization and technical validation of the measurements. The second step co nsisted in the clinical validation by using a retrospective series of 1,003 breast cancers T1 T2, NON1, M0. We report the results of the first step, t ogether with the distributions of the variables and their relationship with classical clinical variables: 1) Using standardized methods and a cytosoli c control, a good reproducibility of measurements was obtained whether assa ys were performed in one (TS, PTK) or in several laboratories (TK). 2) Sign ificantly different distributions of TK and TS were observed between the di fferent centres mainly due to different conditions of storage of tumours an d cytosols. 3) A highly significant correlation was observed between TK, TS and PTK. Highest TK, TS and PTK levels were observed in tumour with high h istological grade or receptor negative tumours. This study clearly illustra tes the importance of quality assurance of multicentre studies.