Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer.
OBJECTIVE
The most reliable method for the diagnosis of peritoneal dissemination of gastric cancer at the present time is cytological examination of ascitic fluid, which is unavailable to patients without ascites or may be inadequate for those with ascites containing few cancer cells. It has been reported recently that human gastric cancer immunoreacted with a monoclonal antibody against pancreatic trypsinogen. We therefore examined the expression of trypsinogen as a new marker for the early diagnosis of peritoneal dissemination of gastric cancer.


METHODS
Pancreatic trypsinogen protein was immunohistochemically stained with a three-step indirect immunoperoxidase method and cationic trypsinogen (trypsinogen-1) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in gastric cancer. Twenty-nine of 30 primary tumors (97%) and all 12 tumors (100%) of the peritoneal seedings immunohistochemically reacted with trypsinogen. Preliminary study for early diagnosis of peritoneal dissemination was carried out for eight more recent patients who showed positive immunoreactivity to trypsinogen protein and expressed trypsinogen- mRNA in the primary tumor. The expression of trypsinogen-1 mRNA was detected by using peritoneal lavage fluid preoperatively collected in these patients.


RESULTS
All three patients in whom peritoneal dissemination was diagnosed at the time of their operation(s) expressed trypsinogen-1 mRNA. One patient, who did not show peritoneal dissemination at the operation but was positive for trypsinogen-1 mRNA detection, later died of the recurrence of peritoneal dissemination.


CONCLUSIONS
These results indicated that trypsinogen protein and trypsinogen-1 mRNA frequently expressed in peritoneal dissemination as well as primary tumors in gastric cancer and detection of trypsinogen-1 mRNA expression was a useful method for early diagnosis in peritoneal dissemination of gastric cancer.
Fujimura
T
T
Second Department of Surgery, School of Medicine, Kanazawa University, Ishikawa, Japan. tphuji@med.kanazawa-u.ac.jp
Ohta
T
T
Kitagawa
H
H
Fushida
S
S
Nishimura
G I
GI
Yonemura
Y
Y
Elnemr
A
A
Miwa
K
K
Nakanuma
Y
Y
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000201:enzymology* / Q000556:secondary; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000556:secondary; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D012194:RNA-Directed DNA Polymerase; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D014362:Trypsinogen / Q000378:metabolism*
D014408:Biomarkers, Tumor; D017931:DNA Primers; D014362:Trypsinogen; D012194:RNA-Directed DNA Polymerase