Decreased expression of DFF45/ICAD is correlated with a poor prognosis in patients with esophageal carcinoma.
BACKGROUND
DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells.


METHODS
The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics.


RESULTS
DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months).


CONCLUSIONS
Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels.
Konishi
Shigeru
S
Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Japan.
Ishiguro
Hideyuki
H
Shibata
Yasuyuki
Y
Kudo
Junzo
J
Terashita
Yukio
Y
Sugiura
Hironori
H
Koyama
Hiroshi
H
Kimura
Masahiro
M
Sato
Atsushi
A
Shinoda
Noriyuki
N
Kuwabara
Yoshiyuki
Y
Fujii
Yoshitaka
Y
D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases