Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: prognostic study on tissue and serum.
OBJECTIVE
The purpose is to study the prognostic significance of tissue expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor (TATI) and serum concentration of trypsinogen-2, trypsin-2-API (complex of trypsin-2 with alpha-1-proteinase inhibitor), and TATI in epithelial ovarian cancer.


METHODS
Expression of trypsinogen-1, trypsinogen-2, and TATI was determined by immunohistochemistry with monoclonal antibodies in tissue sections of tumors from 119 patients with untreated primary epithelial ovarian cancer. Preoperative serum concentrations of trypsinogen-2, trypsin-2-API and TATI were analyzed using specific immunoassays.


RESULTS
Fifty-four percent of the tumors expressed trypsinogen-1, 45% expressed trypsinogen-2, and 30% expressed TATI. In patients with stage III and IV disease, TATI tissue expression (P = 0.002) and elevated TATI concentration in serum (P = 0.048) were associated with adverse cancer-specific and progression-free survival in univariate analysis. In multivariate analysis, TATI tissue expression (P = 0.005), tumor grade (P = 0.0001), histological type (P = 0.02), and stage (P = 0.0005) were independent prognostic factors for adverse cancer-specific survival and TATI tissue expression (P = 0.006) and grade (P = 0.0003) for progression-free survival. In multivariate analysis of all patients and those with advanced disease, serum trypsin-2-API concentration was an adverse prognostic factor for cancer-specific and progression-free survival, and it was independent of stage and histological type of the tumor (P <or= 0.01).


CONCLUSIONS
Tissue expression of TATI and an elevated preoperative serum concentration of trypsin-2-API are strong independent prognostic factors in advanced epithelial ovarian cancer. These results suggest that trypsin expression plays a role in the progression of ovarian cancer. TATI and trypsin-2-API are of potential use as an aid for stratification of randomized studies and for selecting treatment strategies.
Paju
Annukka
A
Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland. annukka.paju@hus.fi
Vartiainen
Juhani
J
Haglund
Caj
C
Itkonen
Outi
O
von Boguslawski
Kristina
K
Leminen
Arto
A
Wahlström
Torsten
T
Stenman
Ulf-Håkan
UH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014357:Trypsin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014361:Trypsin Inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014362:Trypsinogen / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D012334:RNA, Neoplasm; D014361:Trypsin Inhibitors; C064831:PRSS2 protein, human; D014362:Trypsinogen; D014357:Trypsin