Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection.
OBJECTIVE
The extremely unfavorable prognosis of intrahepatic cholangiocarcinoma (ICC), even after surgical resection, is mainly attributed to a high rate of recurrence. The aim of this study was to identify the molecules associated with early recurrence of ICC following resection.


METHODS
Between December 1984 and July 2003, 46 patients with ICC underwent surgical resection. The clinical outcome of these patients was evaluated in view of the time of recurrence. Consequently, we categorized ICC patients into subgroups, based on the clinical results, and screened differentially expressed genes by DNA microarray analysis. Furthermore, the obtained results were validated in an independent sample set by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to assess the expressed genes at the protein level.


RESULTS
The survival of patients with early recurrence, occurring within a year after surgical resection, was significantly poor after surgery and even after recurrence, as compared to that of patients whose recurrence occurred beyond a year after surgery. By the DNA microarray analysis, 13 differentially expressed genes were picked up, and quantitative RT-PCR reaction identified the pancreatic secretory trypsin inhibitor (PSTI) as a candidate gene associated with early recurrence of ICC after resection. This observation was confirmed through examination of an independent set of samples, in which the patients with higher levels of PSTI mRNA expression had significantly shorter recurrence-free survival. Immunohistochemically, PSTI was expressed in the cytoplasm of cancer cells.


CONCLUSIONS
PSTI might be a potential marker for identifying ICC patients with an increased risk of early recurrence after surgical resection.
Tonouchi
Akihiko
A
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ohtsuka
Masayuki
M
Ito
Hiroshi
H
Kimura
Fumio
F
Shimizu
Hiroaki
H
Kato
Masaki
M
Nimura
Yoshinori
Y
Iwase
Katsuro
K
Hiwasa
Takaki
T
Seki
Naohiko
N
Takiguchi
Masaki
M
Miyazaki
Masaru
M
D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D014359:Trypsin Inhibitor, Kazal Pancreatic