In vitro chemosensitivity based on depth of invasion in advanced colorectal cancer using ATP-based chemotherapy response assay (ATP-CRA).
BACKGROUND
Tumors are composed of subpopulations of cells with heterogeneous characteristics that allow for tumor progression and development of treatment resistance. The purpose of this study was to determine if there is heterogeneity in the in vitro chemosensitivity in different invasive sections of a single tumor.


METHODS
Chemosensitivity in advanced colorectal cancer specimens was examined using an ATP-based chemotherapy response assay. Four chemotherapeutic agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, and mitomycin) were used for chemosensitivity studies. Tumor tissues were obtained from the superficial (mucosa/submucosa) and deep parts (muscle/subserosa/serosa), respectively. Twenty patients who had results for both the superficial and deep parts were evaluated.


RESULTS
The chemosensitivity study showed variable cell death rates in both parts of the tumor. Regression analysis showed some correlations with 5-FU and irinotecan, but not with oxaliplatin or mitomycin. With the exception of three patients in whom no drug was recommended, at least one chemotherapeutic drug showed some consistency between the superficial and deep parts of the tumor. Mitomycin was the most frequently active agent for the superficial part. In the deep part, oxaliplatin and mitomycin were the most active agents.


CONCLUSIONS
There may be heterogeneity in the responses to anti-chemotherapeutic agents in advanced colorectal cancer, according to the depth of invasion. Therefore, in clinical situations, chemosensitivity test specimens should be mixed with various parts of the whole tumor in order to obtain representative chemosensitivity and chemoresistance profiles.
Cho
Y B
YB
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
Lee
W Y
WY
Song
S Y
SY
Choi
S H
SH
Shin
H J
HJ
Ahn
K-D
KD
Lee
J M
JM
Kim
H C
HC
Yun
S H
SH
Chun
H-K
HK
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009944:Organoplatinum Compounds / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012044:Regression Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D016685:Mitomycin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin