Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.
BACKGROUND
It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion.


METHODS
We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index.


RESULTS
There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105).


CONCLUSIONS
A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.
Department of Breast Surgery, Nahanishi Clinic, 2-1-9 Akamine, Naha, Okinawa, 901-0154, Japan, nahanisikenta@yahoo.co.jp.
Kentaro
K
Tamaki
Takanori
T
Ishida
Nobumitsu
N
Tamaki
Yoshihiko
Y
Kamada
Kanou
K
Uehara
Minoru
M
Miyashita
Masakazu
M
Amari
Akiko
A
Tadano-Sato
Yayoi
Y
Takahashi
Mika
M
Watanabe
Keely
K
McNamara
Noriaki
N
Ohuchi
Hironobu
H
Sasano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D019394:Ki-67 Antigen / Q000032:analysis* / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human