Single alteration of p53 or E-cadherin genes can alter the surgical resection benefit in an experimental model of colon cancer

PURPOSE. p53 and E-cadherin mutations are associated with a high risk of me tastatic potential and local recurrence after colorectal surgery. LoVo, a h uman colon cancer cell Line expressing a wild-type p53 and a normal E-cadhe rin, was studied. Clone LoVo-XC17 was obtained from LoVo cells transfected with a vector bearing a p53 273his mutation. Clone LoVo-92R4 was obtained f rom LoVo by culture cells with an E-cadherin down-regulation. LoVo, LoVoXC1 7, and LoVo-92R4 were studied for in vivo behavior in a surgical intracolon ic graft model. METHODS: Ten nude mice were used per cell line. A colonic t umor was obtained by tumor implantation into the cecal wall. The cecal tumo r was resected at Day 15; at this time the volumes of the different tumors were similar. RESULTS: Surgical resection of the LoVo tumor led to 100 perc ent disease-free animals at one month. Surgical resection of mice grafted w ith the LoVo-XC17 line did not cure any mice (0/10; P = 0.001). Mice had lo cal recurrences (10/10), mesenteric lymph node metastases (9/10), liver met astases (2/10), and peritoneal carcinomatosis (8/10). Surgical resection of LoVo-92R4 tumors led to cures in 30 percent (3/10), whereas 70 percent had isolated mesenteric lymph node metastases (7/10; P = 0.003). CONCLUSION: I n this model surgical tumor resection was consistently effective for coloni c tumors with functional P53 and E-cadherin, it was consistently ineffectiv e with tumors displaying a mutated p53, and it was partially effective with E-cadherin-deficient tumors. This study shows that the alteration of a sin gle gene can be associated with a profound alteration of surgical resection benefit.