Incidence of apoptosis increases with age in colorectal cancer.
The incidence of cancer increases with advancing age, but the biological behavior of cancer is known to be less aggressive in elderly people. Thus, the proliferative activity and extent of apoptosis of cancer cells were assessed in samples from 163 cases of colorectal cancer focusing on the age of patients, using Ki-67 labeling index (LI) and apoptotic index (AI) by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling method and staining for activated caspase-3. The Ki-67 LI of colorectal cancer ranged from 2.33 to 80.4% (mean 32.2%), while the AI ranged from 0.00 to 14.8% (mean 3.57%). Concerning the aging effect, linear and positive correlations were found for the Ki-67 LI of cancer with age (p<0.05) and the AI of cancer with age (p<0.05). However, in normal colorectal mucosa, aging of patients revealed a significant correlation only with the AI but not with the Ki-67 LI. The AI in earlier stages of cancers (stages 0 and 1) revealed a significant difference between younger cases (age<65) and more elderly cases (age>/=65) (p<0.05), however, the Ki-67 LI did not exhibit a significant difference. Therefore, an increased frequency of apoptosis in colorectal cancer tissues, especially in the earlier stages, may possibly explain the slower growth of colorectal cancers in the elderly. Next, the expressions of several regulatory molecules for the proliferation/apoptosis of tumor cells were determined. The results demonstrated a tendency for stronger and more frequent expressions of c-myc, Bak and Bax despite a rather weaker expression of Bcl-2 in cancer tissues from the elderly compared with those from the younger patients. The potential roles of these regulatory molecules on age-change in the proliferation/apoptosis of colorectal cancers are discussed.
Tanaka
Kenichiro
K
Department of Pathology and Immunology, Aging and Developmental Sciences, Tokyo Medical and Dental University, Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nagaoka
Sakae
S
Takemura
Tamiko
T
Arai
Tomio
T
Sawabe
Motoji
M
Takubo
Kaiyo
K
Sugihara
Kenichi
K
Kitagawa
Masanobu
M
Hirokawa
Katsuiku
K
D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D017209:Apoptosis; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging
D019394:Ki-67 Antigen