A. Becciolini et al., 3H-THYMIDINE LABELING INDEX (TLI) AS A MARKER OF TUMOR-GROWTH HETEROGENEITY - EVALUATION IN HUMAN SOLID CARCINOMAS, Cell proliferation, 30(3-4), 1997, pp. 117-126
Many studies deal with the analysis of cell kinetic, cytogenetic, bioc
hemical and molecular cell biology parameters to identify prognostic f
actors relating to tumour growth but all methods use only a small part
of the total tumour mass. This study is devoted to the analysis of th
e heterogeneity of the growth of human solid tumours assaying prolifer
ative activity by means of 3H-thymidine labelling index (TLI) in a fix
ed number of samples collected in different areas of the lesion (laryn
x and colon cancers), or in different lesions of the same subject (bre
ast and bladder cancers). Each sample (at the macroscopic level) was d
ivided into small fragments (at the microscopic level) and proliferati
ve activity was determined. The analysis of variance for hierarchical
designs demonstrated that in all cases a high component of the varianc
e is attributable to the subjects and to the fragments whereas the var
iance attributable to the different areas is very low. The heterogenei
ty of proliferative activity displays a higher focal variability among
the fragments (microscopic level) compared with that among areas (mac
roscopic level) within subjects, provided an adequate number of fragme
nts and cells are counted. In multiple synchronous carcinoma of the bl
adder the wide variability of proliferation among the single lesions d
emonstrated that it is necessary to analyse all the tumours in a subje
ct because each one is characterized by a different cell growth potent
ial.