Single alteration of p53 or E-cadherin genes can alter the surgical resection benefit in an experimental model of colon cancer.
OBJECTIVE
p53 and E-cadherin mutations are associated with a high risk of metastatic potential and local recurrence after colorectal surgery. LoVo, a human colon cancer cell line expressing a wild-type p53 and a normal E-cadherin, was studied. Clone LoVo-XC17 was obtained from LoVo cells transfected with a vector bearing a p53 273his mutation. Clone LoVo-92R4 was obtained from LoVo by culture cells with an E-cadherin down-regulation. LoVo, LoVo-XC17, and LoVo-92R4 were studied for in vivo behavior in a surgical intracolonic graft model.


METHODS
Ten nude mice were used per cell line. A colonic tumor was obtained by tumor implantation into the cecal wall. The cecal tumor 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 percent disease-free animals at one month. Surgical resection of mice grafted with the LoVo-XC17 line did not cure any mice (0/10; P = 0.001). Mice had local recurrences (10/10), mesenteric lymph node metastases (9/10), liver metastases (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).


CONCLUSIONS
In this model surgical tumor resection was consistently effective for colonic tumors with functional p53 and E-cadherin, it was consistently ineffective with tumors displaying a mutated p53, and it was partially effective with E-cadherin-deficient tumors. This study shows that the alteration of a single gene can be associated with a profound alteration of surgical resection benefit.
Pocard
M
M
Cytogénétique Moléculaire et Oncologie, Institut Curie, Paris, France.
Debruyne
P
P
Bras-Gonçalves
R
R
Mareel
M
M
Dutrillaux
B
B
Poupon
M F
MF
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000818:Animals; D015820:Cadherins / Q000235:genetics*; D002430:Cecal Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009368:Neoplasm Transplantation; D011379:Prognosis; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D015820:Cadherins; D016159:Tumor Suppressor Protein p53