Correlation of allelic losses and clinicopathological factors in 504 primary breast cancers.
BACKGROUND
We have defined 18 chromosomal regions in which allelic losses were frequent among breast cancers. We examined whether specific allelic losses might correlate with any clinicopathological factors.


METHODS
We tested DNA from matched normal and tumor tissues for loss of heterozygosity (LOH) at 18 microsatellite loci from a cohort of 504 patients who had undergone surgery for breast cancer.


RESULTS
LOH at 3p14.3 correlated with a larger size of tumor (greater than 2 cm). LOH at 1p22, 3p25.1, 3p14.3, or 17q21.1 correlated with loss of estrogen receptors. LOH at as many as eleven regions correlated with loss of progesterone receptor, suggesting that these represent general phenomena associated with progression of cancer. Above all, allelic losses at 11q23-24, 13q12, 17p13.3, or 22q13 significantly correlated with lymph-node metastasis (11q23-24, p= 0.0042; 13q12, p=0.0207; 17p13.3, p=0.0478; 22q13, p=0.0162).


CONCLUSIONS
These results suggest that some clinical characteristics of breast cancers are determined by loss of tumor suppressor genes present at specific chromosome regions. Especially, LOH at 11q23-24, 13q12, 17p13.3, and 22q13 is a significant predictor of lymph-node metastasis for patients who have undergone surgery for breast cancer, and may serve as a negative prognostic indicator.
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan.
Takemitsu
T
Nagahata
Akira
A
Hirano
Yoshihito
Y
Utada
Shinichi
S
Tsuchiya
Kaoru
K
Takahashi
Takashi
T
Tada
Masujirou
M
Makita
Fujio
F
Kasumi
Futoshi
F
Akiyama
Goi
G
Sakamoto
Yusuke
Y
Nakamura
Mitsuru
M
Emi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002877:Chromosomes, Human / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002882:Chromosomes, Human, Pair 13; D002886:Chromosomes, Human, Pair 17; D002892:Chromosomes, Human, Pair 22; D015331:Cohort Studies; D046508:Culture Techniques; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D004273:DNA, Neoplasm; D005819:Genetic Markers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone