HETEROGENEITY OF INTRATUMOR PROLIFERATIVE ACTIVITY IN PRIMARY BREAST-CANCER - BIOLOGICAL AND CLINICAL ASPECTS

The present retrospective study was undertaken to verify whether the e xtent of intratumour proliferative activity variation or the method of quantifying tumour proliferative activity is related to biological ch aracteristics and clinical outcome in a series of operable node-negati ve breast cancer patients. For tumour proliferative activity evaluatio n, the H-3-thymidine autoradiographic assay was used. After incubation of 3-8 samples from different areas of the equatorial section of each tumour for 1 h at 37 degrees C with H-3-thymidine, the following meth ods were used for evaluation of tumour cell labelling: mean tumour lab elling index (LI), the highest labelling value from a specific area (L I-max), and the extent of intratumour labelling variation from several samples (LI-CV). LI-max was related to ER and PgR status, and linearl y correlated with LI (c.c. = 0.92, P< 10(-6)) whereas LI-CV was indepe ndent of tumour size, grade ER and PgR status, but dependent on the nu mber of tumour samples analysed for each tumour. After 5 years of medi an follow-up, disease-free survival was only related to tumour size (T 1 versus T2: 84 versus 64%, P < 0.04 by log rank analysis) and differe nt LI values (low versus high H-3-Tdr-LI: 86 versus 61%, P < 0.03 by l og rank analysis). LI-max and LI-CV values were not significantly rela ted to clinical outcome. Cox multivariate analysis confirmed the indep endent prognostic value of LI and tumour size on disease-free survival .