Expression of Trypsinogen-1, Trypsinogen-2, and Tumor-Associated Trypsin Inhibitor in Ovarian Cancer

Abstract

Purpose: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 ␣-1-proteinase inhibitor), and TATI in epithelial ovarian cancer.Experimental Design: 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 < 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.

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

“…The presence of TATI in tumors is a marker of adverse prognosis for hepatocellular carcinoma (HCC), bladder, kidney and mucinous ovarian cancers (Stenman, 2002;Antila et al, 2006;Lee et al, 2007;Paju et al, 2007). In patients with stage III and IV ovarian cancers, TATI tissue expression and elevated TATI concentration in serum were associated with adverse cancer-specific and progression-free survival (Paju et al, 2004). Of note, TATI overexpression correlates with anchorage-independent growth, high stage HCC, portal vein invasion, early tumor recurrence and metastasis (Lee et al, 2007).…”

Prognostic molecular markers in cholangiocarcinoma: A systematic review

“…Having previously been shown to be an independent prognostic marker in bladder (141), ovarian (142) and renal(143) carcinomas, PSTI expression was investigated in CC specimens. High expression was associated with decreased recurrence-free survival on univariate analysis(144).…”

Identification of pancreatic juice proteins as biomarkers of pancreatic cancer

“…PRSS2 has been reported to be highly expressed in several cancers, e.g., pancreatic (17), gastric (18), colorectal cancer (19), cholangiocarcinoma (20) and esophageal squamous cell carcinoma (21). The serum concentration of the inactive PRSS2 preproprotein was significantly higher in ovarian cancer patients with high stage compared to those with a low stage (22). Elevated serum levels of PRSS2 and PRSS2-API have been observed in a majority of patients with cholangiocarcinoma and pancreatic cancer (23).…”