Endogenous TNF inducibility and prognosis of colorectal cancer

We have demonstrated that the inducibility of endogenous TNF (en-TNF) by colorectal tumor cells is a factor in predicting a patient prognosis. The prognoses of colorectal tumor patients with the K-ras gene mutations in their tumors were poorer to those of patients with the wild type gene. Therefore, we analyzed the possible relationship between the inducibility of en-TNF by colorectal tumor cells during the follow-up of patients with K-ras mutations.

In 62 of 154 Dukes Stage C patients who received curative operation from June 1988 to June 1997, the prognoses in terms of the tumor-free rate and survival rate were compared with the inducibility of en-TNF by colorectal tumor cells, which were classified into three groups: grade 1: > or = 500 pg/ml, grade 2: 100-500 pg/ml, and grade 3: < 100 pg/ml. Regardless of the Dukes Stage of the patients, the K-ras gene was analyzed in 21 whose colorectal tumor cells were classified as grade 1: 8, grade 2: 4, and grade 3: 9.

The tumor-free rate of the patients with grade 1 was significantly higher than that of the patients with grade 3, and the survival period of the patients with grades 1 and 2 was significantly longer than that of the patients with grade 3. Possible mutations disorder of K-ras were observed in 37.5% (grade 1), 50.0% (grade 2), and 88.9% (grade 3) of cases, respectively.

The prognostic value of the inducibility of en-TNF by colorectal tumor cells from colorectal cancer patients who received curative operation at Dukes Stage C was confirmed. It is suggested that K-ras mutation may affect patient prognosis through modulation of the quality and/or quantity of cytokines such as TNF produced by tumor cells.