Genetic detection of liver micrometastases that are undetectable histologically

Predicting liver metastasis from colon cancer is essential for improving its prognosis. We studied to what extent genetic detection of cancer cells in the resected liver tissue can predict the incidence of macroscopic liver metastasis with a similar mouse model to clinical colorectal cancer that causes a several decade percentage of metachronous hepatic metastases after resection of the primary lesions.

A LS174T human colorectal cancer cell suspension was injected into the spleens of nude mice. One to 10 days after splenic injection, 3 x 3 mm of liver tissue was removed, and a splenectomy was performed. Liver tissue was used for genetic detection and histological examination. Five weeks after splenic injection, the number of macroscopic metastases on the surface of the liver was counted.

Eight of the 45 cases were positive for tumor cells in liver tissue genetically, while only 1 was positive for tumor cells histologically. Macroscopic liver metastases were seen 5 weeks after splenic injection in 11 of 37 (29.7%) cases negative for tumor cells genetically and in 8 of 8 (100%) cases positive for tumor cells genetically. Five or more metastases were seen in 3 of 37 (8.1%) cases negative for tumor cells genetically and in 7 of 8 (87.5%) cases positive for tumor cells genetically.

The cases which were positive for tumor cells in liver tissue genetically at the time of splenectomy had more significantly macroscopic liver metastases some weeks later than the cases negative for tumor cells. This study suggests that if micrometastasis was detected genetically, the development of metachronous macroscopic liver metastasis could be predicted.