Do aggressive subclones within primary colorectal cancer give rise to liver metastases?

Primary colorectal cancers and hepatic metastases from 24 patients have been compared according to type, grade, DNA content as measured by flow cytometry, and expression of two differentiation antigens and carcinoembryonic antigen (CEA). The primary and secondary tumours were histologically indistinguishable in 23 out of 24 cases. DNA content differed between primary and metastasis in only six cases. Immunohistochemical profiles were usually the same in the primary and metastasis. In particular, heterogeneous expression by the primary was mirrored in the metastasis. In 17 out of 24 (70.1%) patients the primary and metastasis were indistinguishable by all six parameters. In one of these, the liver metastasis had been removed 14 years 10 months after the primary tumour. It is concluded that DNA content as measured by flow cytometry may remain stable for long periods and that the differences shown in this study may simply be due to inadequate sampling of the primary tumour. Phenotypic heterogeneity may be epigenetic and not indicative of genetic instability and cannot be used to track the progression of subclones.