High cell kinetics is associated with amplification of the int-2, bcl-1, myc and erbB-2 proto-oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers.
Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH+AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series.
Contegiacomo
A
A
Department of Experimental Medicine, University of Rome La Sapienza, Italy.
Pizzi
C
C
De Marchis
L
L
Alimandi
M
M
Delrio
P
P
Di Palma
E
E
Petrella
G
G
Ottini
L
L
French
D
D
Frati
L
L
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011519:Proto-Oncogenes