Candidate host marker for peritoneal dissemination.
BACKGROUND
Mesothelial cell injury is common in peritoneal dissemination (PD) of cancer cells. The plasminogen activator system, including urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1), plays an important role in repair of the peritoneum damaged by several types of peritonitis. We investigated and compared the expression of uPA and PAI-1 in the peritoneum of cancer patients with and without PD.


METHODS
Cancer cell-positive peritoneum and cancer cell-negative peritoneum specimens were obtained from 11 patients with PD, while peritoneum specimens were also obtained from 24 patients without PD. The presence or absence of cancer cells in the peritoneal tissues was confirmed by both hematoxylin-eosin staining and reverse transcriptase-polymerase chain reaction (RT-PCR) detection of carcinoembryonic antigen (CEA) mRNA. uPA and PAI-1 mRNA expression in these peritoneal tissues was determined by RT-PCR and the proteins were localized immunohistochemically. The results were compared statistically.


RESULTS
uPA mRNA was expressed in the cancer cell-positive peritoneum from 9 of the 11 (81.8%) patients with PD; PAI-1 mRNA was expressed in the peritoneal tissue from 10 of (91.9%) these patients. Either uPA or PAI-1 mRNA was expressed in the cancer cell-negative peritoneum from 8 (72.7%) of the 11 patients with PD, whereas uPA mRNA was expressed in none of the peritoneal tissues from the 24 patients without PD and PAI-1 mRNA was expressed in specimens from 4 (16.7%) of these patients. Immunohistochemical analysis revealed uPA and/or PAI-1 in the mesothelial cells and submesothelial fibroblasts in cancer cell-negative peritoneum from the patients with PD but not in peritoneum from the patients without PD.


CONCLUSIONS
uPA transcription in the peritoneum may be a host marker indicating the existence of PD.
Hashizume
Kentarou
K
Department of Cancer Therapy and Research, Kyushu University, Fukuoka, Japan.
Uchiyama
Akihiko
A
Sasaki
Nobuhiko
N
Noshiro
Hirokazu
H
Morisaki
Takashi
T
Tanaka
Masao
M
Katano
Mitsuo
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000556:secondary; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator