Immunohistochemical Study on Pancreatic Secretory Trypsin Inhibitor (PSTI) in Gastric Carcinomas

Abstract

The expression of pancreatic secretory trypsin inhibitor (PSTI) was studied immunohistochemically in 106 cases of gastric carcinoma. Of the 45 intestinal-type carcinomas, 34 cases (76%) expressed PSTI: 15 (63%) of 24 early carcinomas and 19 (90%) of 21 advanced carcinomas, the incidence being significantly different (P less than 0.05). Furthermore, in the intestinal-type carcinomas, a significant correlation was observed between PSTI expression and clinical stage or nodal involvement. On the other hand, of the 61 diffuse-type carcinomas, including 27 early and 34 advanced carcinomas, 54 cases (89%) were positive for PSTI; a high incidence of the PSTI expression was observed in both early and advanced carcinomas, being 93% and 85%, respectively. Moreover, PSTI-positive cells were localized in more than half of the early diffuse-type gastric carcinomas at the invading zone of the surrounding tissues. The incidence of PSTI expression in advanced scirrhous-type carcinomas (100%) was significantly higher than that (76%) in medullary-type ones (P less than 0.05). Thus, the present findings, together with the previous reports that PSTI stimulates 3H-thymidine incorporation into DNA in human fibroblasts, suggest that the PSTI expressed in gastric carcinomas may possibly possess a biologic function responsible for the tumor growth and progression and for the stromal proliferation of fibrous tissues.

Expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer

“…Nevertheless, several investigators have recently shown that PSTI may have functions other than the inhibition of trypsin activity, such as growth factor action (Niinobu et al, 1986;Ogawa et al, 1985Ogawa et al, , 1987. In fact, we have shown that the expression of PSTI in gastric cancer may possibly be associated with tumour growth and progression (Higashiyama et al, 1990).Although it has been reported that PSTI may be expressed in villous adenoma of the colon (Bohe et al, 1986;Tomita et al, 1987), there has been-u-study of the expression of PSTI in colorectal cancer, except for the preliminary report (Ogawa et al, 1987). In the present study, we demonstrate that colorectal cancer may also express PSTI, not only by immunohistochemical analysis for detection at the product level but also by in situ hybridisation and Northern blot hybridisation for detection at the transcriptional level.…”

“…Nevertheless, several investigators have recently shown that PSTI may have functions other than the inhibition of trypsin activity, such as growth factor action (Niinobu et al, 1986;Ogawa et al, 1985Ogawa et al, , 1987. In fact, we have shown that the expression of PSTI in gastric cancer may possibly be associated with tumour growth and progression (Higashiyama et al, 1990).…”

“…Its physiological role has been considered to prevent the premature activation of trypsin in the pancreatic acini and ducts (Kazal et al, 1948). However, PSTI has also been demonstrated in various malignant cell lines and tissues, including pancreatic cancer, lung cancer, gynaecological cancer, and gastric cancer (Higashiyama et al, 1990;Ogata, 1988;Ogawa et al, 1987;Tomita et al, 1987;Ueda et al, 1989); the physiological role of PSTI in neoplastic tissue remains unknown. Nevertheless, several investigators have recently shown that PSTI may have functions other than the inhibition of trypsin activity, such as growth factor action (Niinobu et al, 1986;Ogawa et al, 1985Ogawa et al, , 1987.…”

Pancreatic secretory trypsin inhibitor gene is highly expressed in the liver of adult‐onset type II citrullinemia

“…Its role has been considered to be a specific inhibitor that prevents autoactivation of trypsinogen in the pancreas and pancreatic juice [41]. Later studies showed that PSTI was also expressed in some extrapancreatic normal tissues [39,4345] and in various cancers, including pancreatic [34], colorectal [35], gastric [36], lung [37], and hepatocellular [38] cancers. It was found that the serum concentration of immunoreactive PSTI is elevated after surgery, trauma and severe infection [45][46][47], suggesting that PSTI is an acute phase reactant.…”

“…These phenomena imply that PSTI has other physiological and pathological roles in addition to the inactivation of trypsin. Several papers suggest that tumor-derived PSTI acts as autocrine or paracrine growth factor [46,[50][51][52][53][54], and is associated with the tumor growth of stromal proliferation of fibrous tissues [36,37], although it has been reported recently that the evaluation of tumor-derived PSTI as a paracrine or autocrine growth factor is not definite and needs confirmation [55]. The hPSTI mRNA expression in type II citrullinemia patients was equivalent to the level in hepatic cancer portions (Figs.…”