Clinical significance of stromal apoptosis in colorectal cancer.
BACKGROUND
Epithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.


METHODS
Total apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.


RESULTS
Epithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (< or = median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05-3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (< or = median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17-2.35), 1.62 (1.15-2.29) and 1.69 (1.01-2.85), respectively.


CONCLUSIONS
Stromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC.
Koelink
P J
PJ
Department of Gastroenterology-Hepatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Sier
C F M
CF
Hommes
D W
DW
Lamers
C B H W
CB
Verspaget
H W
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D015203:Reproducibility of Results; D017154:Stromal Cells / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D000951:Antigens, Neoplasm; D007633:Keratins; D053148:Caspase 3