Apoptosis in breast cancer and its relationship to clinicopathological characteristics and prognosis.
OBJECTIVE
Apoptosis is essential to maintain homeostasis in living organisms and occurs in a variety of tissues in response to both physiological and pathological stimuli. In breast cancer, most cytotoxic drugs and hormonal treatments induce apoptosis. We studied the relationships between apoptosis and clinicopathological variables or prognosis in 143 patients with operable breast cancer.


METHODS
Apoptosis was numerically graded in 5 consecutive 40x high-power fields (HPF) of hematoxylin-eosin (H&E) stained sections, since we showed that there was a significant correlation of H&E staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining.


RESULTS
The average number of apoptotic cells was 19.9 (0 approximately 168)/5 HPF, and cases were classified into 3 groups based on the number of apoptotic cells/5HPF: 0 to 10, 11 to 30, and 31+. The level of apoptosis increased with increasing size of the tumor, and apoptosis was rarely seen in tumors with positive ER or lower proliferative activity, as assessed by DNA polymerase alpha. As shown by DNA content analysis, apoptotic cells were observed more frequently in tumors with low G1 and high S-phase fractions. In addition, apoptosis was correlated with overexpression of p53 and poor prognosis. Although apoptosis did not correlate with EIC (extensive intraductal component) status, tumors with comedo component had higher values of apoptosis than those without comedo component.


CONCLUSIONS
In breast cancer, apoptosis might reflect biological behavior, namely a higher degree of biological aggressiveness and unfavorable prognosis.
Nishimura
R
R
Department of Surgery, Kumamoto City Hospital, Kumamoto, Japan.
Nagao
K
K
Miyayama
H
H
Matsuda
M
M
Baba
K
K
Matsuoka
Y
Y
Yamashita
H
H
Fukuda
M
M
Higuchi
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D002453:Cell Cycle; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D004273:DNA, Neoplasm; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53