Summary To evaluate the clinical significance of serum levels of hepatocyte growth factor (HGF) in colorectal cancer patients, we measured the venous and portal concentrations of HGF in 60 patients. The tissue concentrations in the tumour and adjacent normal mucosa were also determined. The serum HGF concentration for the peripheral venous blood of the patients was significantly higher than that in normal controls. The content of HGF in cancer tissue was also significantly higher than that in normal mucosa, and it was correlated with the serum HGF concentration for the peripheral venous blood. The serum concentration of HGF reflected pathological features, including tumour size and lymph node or liver metastasis, and it showed an association with various preoperative nutritional parameters and the preoperative haemoglobin level. The serum HGF concentration was also correlated with the serum concentrations of immunosuppressive acidic protein and interleukin-6, indices of the host's immunological condition. Serum HGF seems to be a useful index of the disease status of patients with colorectal carcinoma.Keywords: hepatocyte growth factor; nutritional status; immunological status; colorectal cancer Hepatocyte growth factor (HGF) is a multifunctional cytokine that is the most potent known stimulator of hepatocyte growth and DNA synthesis Kaneko et al, 1992). HGF has also been recognized as a tumour-disseminating factor (Weidner et al, 1991;Mayer et al, 1993;Tannapfel et al, 1994). In several experimental studies, evidence has been acquired of a relation of HGF to the progression of tumour cells . Among the particularly important biological activities of HGF in tumour cells is its capacity to increase epithelial cell proliferation and motility (Gherardi et al, 1990). In clinical studies, a relationship between the concentration of HGF in serum or cancer tissue and the progression of disease has been noted in patients with gastric cancer (Taniguchi et al, 1997), oesophageal cancer (Takada et al, 1995) and breast cancer (Yamashita et al, 1994;Taniguchi et al, 1995). However, there are no reports regarding the clinical relevance of HGF in patients with colorectal carcinoma.Malnutrition or immunosuppression are involved in the development of life-threatening complications in patients with malignancies (Braga et al, 1988;Nishi et al, 1988;Dannhauser et al, 1995;Triantafillidis et al, 1995;Windsor et al, 1995;Goransson et al, 1996). Patients with advanced cancer and cachexia typically demonstrate modestly increased rates of energy expenditure with concomitant diminished food intake. These metabolic changes may be due to mediators released by the tumour or by the host (Keller, 1993). Recently, the role of cytokines in these metabolic changes was emphasized (Gambardella et al, 1997). In addition, the relationship between cytokines and an immunosuppressive substance has also been highlighted (Tanaka et al, 1993 The objective of this study was to evaluate the relationship between serum HGF concentration and clinicopathological ...

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lmmunoreactive transforming growth factor-p 1 (TGF-p 1 ), its receptor (TGFR), bcl-2 protein, and p 5 3 protein were stained in 47 samples of normal colonic mucosa and 33 samples of colorectal adenoma, with the aim of exploring an alternate, novel pathway of colorectal tumorigenesis. There was no difference in the percentage of cells positive for TGF-p 1 immunoreactivity between normal mucosae and adenomas. TGFR immunoreactivity was detected in a significantly higher percentage of normal mucosae than of adenomas ( p < 0.05). Bc/-2 protein and p53 protein immunoreactivities were detected in a significantly higher percentage of adenomas than of normal mucosae ( p < 0.0 1 ). Expression of these immunoreactive proteins did not correlate with any of the clinicopathological features of adenomas. except for a significant negative correlation between TGFR expression and large tumor size ( p < 0.05) and a positive correlation between p53 protein expression and the grade of dysplasia ( p <0.05). These findings indicate that (1) TGF-P1 plays little role in the tumorigenesis of colorectal adenomas, (2) TGFR is lost in most adenomas during tumorigenesis, (3) bcl-2 protein plays an important role in transformation of normal mucosa into adenoma, and (4) p 5 3 protein is involved in the very early phase of malignant transformation from adenoma to carcinoma. (Dig Endosc 1997 ; 9 : 272-277)

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