T he report by Shim et al. 1 in this issue of Cancer presents interesting data regarding the potential use of serum transforming growth factor (TGF)-1 levels as a tumor marker in patients with colorectal carcinoma. Their findings suggest that TGF- may be helpful in predicting extent of disease and the likelihood of disease recurrence and survival.
Under normal circumstances TGF-1 stimulates mesenchymal cell proliferation and inhibits proliferation of epithelial cells. In the human colon, TGF-1 inhibits the proliferation of cells as they move out of the intestinal crypt to the tip of the villus. 2 Loss of this growth inhibition frequently is observed in colorectal carcinoma. The actions of TGF-1 are mediated by binding to type 1 and type 2 TGF-1 receptors and it has been suggested that the lack of growth inhibition by TGF-1 in colorectal carcinoma may be caused by a lack or decreased expression of TGF-1 receptors.
Many previous studies have examined the relation between TGF-1 and disease progression in patients with colorectal carcinoma. Several investigators have studied TGF-1 expression in colorectal tumor tissue, whereas others have examined the plasma TGF-1 level and its association with disease progression. For example, Friedman et al. 3 showed that patients whose tumors stained intensely for TGF-1 were much more likely to have recurrent disease than those whose tumors did not stain intensely. This was independent of lymph node status and degree of differentiation of the primary tumor.
The findings of the current study by Shim et al. 1 are consistent with previous work. Robson et al. 4 noted a very significant relation between tumor expression of TGF-1 and survival. The 3-year survival rate was 80% in patients whose tumors were TGF-1 negative and only 40% in those whose tumors were positive for TGF-1. Although the numbers did not reach statistical significance in a group of patients considered to have undergone curative surgical resections, there was a highly significant relation in the group of patients who underwent only palliative resection. In the latter group, the 3-year survival rate was 60% in patients whose tumors were TGF-1 negative, but only 5% in those patients whose tumors were positive for TGF-1.
Tsushima et al. 5 also found elevated levels of TGF-1 in patients