HIGH-LEVELS OF TRANSFORMING GROWTH-FACTOR-BETA-1 CORRELATE WITH DISEASE PROGRESSION IN HUMAN COLON-CANCER

Several genes have been identified that play a role in colon cancer de velopment, However, less is known about factors that increase the rate of progression of colon cancers to metastasis, One candidate is trans forming growth factor beta 1 (TGF beta 1), which can enhance the aggre ssiveness of human colorectal cell lines in vitro and in vivo. The amo unt of TGF beta 1, TGF beta 2, and TGF beta 3 protein isoforms express ed in primary site colorectal cancers were measured to determine wheth er any correlation existed between protein levels and disease recurren ce in a series of Memorial Sloan-Kettering Hospital patients who under went potentially curative resections, Intense staining for TGF beta 1 correlated significantly (P < 0.0013; odds ratio, 18) with disease pro gression to metastasis and was independent of nodal status and the deg ree of differentiation of the primary tumor, Therefore, in this study, patients with high TGF beta 1 protein levels in their primary site co lorectal cancer were 18 times more likely to experience recurrence of their disease than were patients whose tumors exhibited low levels of TGF beta 1. In this case-control study, patients whose cancer recurred and those remaining cancer free were age and sex matched, The disease recurred at a mean of 26.8 +/- 4.3 (SE) months, whereas the mean foll ow-up time in patients whose disease did not recur was over twice as l ong, 57.3 +/- 6.6 months, Ninety-four % of the patients in each group were node positive at the time of resection, with equal mean numbers o f positive nodes per patient, No correlation between disease progressi on and abundance of either TGF beta 2 or TGF beta 3 was observed, Thus , elevated levels of TGF beta 1 protein in the primary site colorectal cancer correlate with an increased risk for progression to metastasis .