Scand J Clin Lab Invest 1991; 51 (Suppl. 207): 71-73

Tumor-associated trypsin inhibitor in pancreatic diseases Scand J Clin Lab Invest Downloaded from informahealthcare.com by Flinders University of South Australia on 12/26/14 For personal use only.

E. A R O A S I O & P . P I A N T I N O * Divisione di Gastroenteriologia, Osp. S. Giovanni Battista, Sede Molinette, USL n.8, Torino. *Laboratorio Analisi, Instituto di Oncologia, USL n. 1, Torino

Aroasio E, Piantino P. Tumor-associated trypsin inhibitor in pancreatic disease. Scand J Clin Lab Invest 1991; 51 (Suppl. 207): 71-73. We have evaluated tumor-associated trypsin inhibitor (TATI) as a marker for pancreatic and hepatic cancer. Of the patients studied 52 had pancreatic cancer, 30 primary liver cancer, 32 chronic pancreatitis, 25 biliary tract inflammatory disease, and 28 liver cirrhosis. A considerable number of falsely elevated values were observed in benign biliary diseases and in chronic relapsing pancreatitis. In pancreatic cancer the sensitivity of TATI was 63% while that of CEA was 40% and of CA19-9 77%. TATI is a marker of pancreatic disease but it does not differentiate between pancreatitis and pancreatic cancer. In liver cancer TATI and AFP has similar sensitivity and specificity. Key words: Tumor markers, pancreatic disease, tumor-associated trypsin inhibitor

E . A r o a s i 0 , Divisione di Gastroenteriologia, Osp. S. Giovanni Battista, Sede Molinette, USL n.8, Torino

Tumor associated trypsin inhibitor (TATI) is a 6000 Dalton peptide isolated from the urine of a patient with ovarian cancer [l, 21. Elevated concentrations of TATI have been found in serum and urine of patients with pancreatitis, pancreatic cancer and benign biliary disease [3, 41. The amino acid sequence of TATI indicates identity with pancreatic secretory trypsin inhibitor (PSTI) [2]. By immunohistochemistry PSTU TATI has been shown to be present in pancreatic cancer, but also in normal pancreatic tissue adjacent to the carcinoma [3].

The aim of this work was to evaluate TATI as a marker for pancreatic and hepatic tumors. For comparison we also measured carcinoembryonic antigen (CEA) CA 19-9 and AFP. MATERIALS AND METHODS We studied 167 patients of which 32 had chronic pancreatitis, 25 benign diseases of the biliary tract, 28 liver cirrhosis, 52 pancreatic cancer, 22 of which were resectable, and 30 liver cancer. 71

72

E. Aroasio et al.

TABLE I. Frequency of elevated levels of TATI, CEA and CA19-9 in pancreatic and hepatobiliary diseases. N

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Pancreatic cancer -With metastasis - Without metastases

Chronic pancreatitis Relapse - Remission Benign biliary disease -

TATI

CEA

>32 M A

>5

CA 9-9 A 0 kUA

MA

52 30 22

33 (63%) 22 (73%) 11 (50%)

21 (40%) 13 (43%) 8 (36%)

13 (59%) 27 (90)% 13 (59%)

32 14 18

16 (50%)

2 (6%) 2 (14%)

0

5 (15%) 4 (26%) 1(6%)

25

8 (32%)

2 (8%)

8 (32%)

TATI was measured by radioimmunoassay using a kit from Farmos Diagnostica. The immunoradiometric assay for CEA was from Ares-Serono, that for CA19-9 from CIS Diagnostici and that for alpha-fetoprotein (AFP) from Sorin. The cut-off value for AFP was 20 pg/l, for TATI 32 pgA, for CEA 5 pgfl and for CA19-9 40 kUA. RESULTS Table I shows the result for patients with pancreatic disorders. The serum concentrations of TATI were elevated in 64%of the patients with pancreatic cancer. In patients with advanced cancer TATI had a sensitivity of 73%. CA19-9 had a higher sensitivity, 90%, whereas CEA was less sensitive (43%). Elevated levels TATI were observed in 50% of the patients with chronic pancreatitis and in 32% of those with inflammatory cholecystic disease. The corresponding figures for CEA were 8% and 6% and those forCA19-9 were 15% and 32%, respectively. In liver cancer the frequency of elevated levels of TATI and AFP was similar, 73% and 80%, respectively. The rate of false positive results was also similar, 21% for TATI and 18% for AFP (Table 11). We monitored some patients with chronic relapsing pancreatitis during the acute phase of the disease. The levels of amylase and TATI did not follow the same path. During a 6months follow-up of a patient with a pancreatic pseudocyst the amylase levels normalized within a month while TATI became normal only after 4 months.

12 (85%) 4 (22%)

DISCUSSION T h e serum levels of TATI may become elevated not only in pancreatic and hepatic tumors but also in benign pancreatic and hepatobiliary diseases. In liver cancer TAT1 showed high sensitivity and the rate of false positive results was similar to that of AFP. The false positives were probably associated with hepatic necrosis and subsequent regeneration. The elevation of TATI in pancreatitis may be caused by direct release of the peptide by pancreatic acinar cells. We think that an increased production of proteolytic enzymes induces a corresponding production of protease inhibitors. In benign obstruction of the common bile duct due to bile stones of cholangitis the source of the elevated TATI levels is not clear. TATI has been detected in biliary epithelium by immunohistochemistry by Haglund et al. [3]. Therefore release of TATI from this source due to tissue damage could cause elevated serum levels in connection with inflammation. In conclusion, the usefulness of TATI in the differential diagnosis between pancreatic cancer and benign hepatobiliary and pancreatic diseases is limited by the fact that TATI also may be elevated in pancreatitis and biliary obstruction. In liver cancer TATI shows results similar to TABLE11. Frequency of elevated levels of TATI, CEA and CA19-9 in hepatic cancer and liver

cirrhosis.

Liver cancer Liver cirrhosis

30 28

22 (73%) 6 (21%)

24 (80%) 5 (18%)

TATI in pancreatic disease

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those of AFP, but the number of patients studied is too small to allow us to draw final conclusions.

REFERENCES 1. Stenman U-H, Huhtala M-L, Koistinen R,

Seppala M. Immunochemical demonstration of an ovarian cancer associated urinary peptide. Int J Cancer 1982; 30: 53-7. 2. Huhtala M-L, Pesonen K, Kalkkinen N, Stenman U-H. Purification and characterization of a

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tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer. J Biol Chem 1982; 257: 13713-6. 3. Haglund C, Huhtala M-L, Halila H, Nordling S, Roberts P, Scheinin T, Stenman U-H. Tumourassociated trypsin inhibitor, TATI, in patients with pancreatic cancer, pancreatitis and benign biliary disease. Brit J Cancer 1986; 5 4 297303. 4. Lasson A, Borgstrom A, Ohlsson K. Elevated pancreatic secretory trypsin inhibitor levels during severe inflammatory disease, renal insufficiency, and after various surgical procedures. Scand J Gastroenterol 1986; 21: 1275-80.

Tumor-associated trypsin inhibitor in pancreatic diseases.

We have evaluated tumor-associated trypsin inhibitor (TATI) as a marker for pancreatic and hepatic cancer. Of the patients studied 52 had pancreatic c...
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