Cytokinetic investigations in human breast cancer by flow cytometrically recorded DNA/protein distributions.
This prospective study characterizes T1-T2 breast carcinomas (N = 114) and fibroadenomas (N = 16) by cell kinetic parameters derived from flow cytometrically recorded DNA/protein histograms. Ploidy level, cell cycle distribution and the number of cell subpopulations (SP) characterized by correlating DNA and protein values were assessed. The subpopulations were derived from the three-dimensional plot. The estrogen receptor (ER) status was determined biochemically (N = 61). Within the G1/0 cell peak 1-6 SP were evident in principle. Depending on the number of SP, two subsets were established: subset 1 with < or = 2 SP, subset 2 with > or = 3 SP. They differed significantly in proliferative activity expressed in the percentage of cells in the G2M phase. Subset 2 showed the higher activity. Analysis of subset distributions revealed that subset 1 prevails in favourable prognostic cases as ER positive cases (P < 0.03), lobular carcinomas (P < 0.01) and LN- cases (P < 0.03), whereas subset 2 prevails in the unfavourable counterparts. Analysis of variance showed that the main effect on proliferative activity indicated by G2M% is due to subpopulation composition rather than histologic type, nodal status or ER status (P < 0.01, P < 0.002, P < 0.05), not even due to ploidy level (P < 0.0001). The rationale for subset stratification may be cytogenetic variability connected with protein content heterogeneity accounting for kinetic SP.
Weiss
H
H
Max-Delbrück-Centrum for Molecular Medicine, Berlin, Germany.
Görlich
M
M
Frege
J
J
Granetzny
A
A
Streller
B
B
Nitschke
U
U
Weiher
U
U
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis
D004273:DNA, Neoplasm; D011506:Proteins; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen