Metastatic colorectal cancer cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone.
Dr Leonie Mekenkamp and colleagues from the Netherlands identified clinicopathological features and chromosomal aberrations of primary tumors associated with organ-specific colorectal cancer metastasis.
Clinicopathological features were investigated in patients with colorectal cancer who had exclusively hepatic versus exclusively extrahepatic metastases.
The team of doctors screened a total of 139 primary tumors of patients with hepatic and extrahepatic metastases for chromosomal aberrations by microarray-based comparative genomic hybridisation, and the findings were validated in an independent set of 80 primary tumors.
A publicly available database was used to correlate chromosomal aberrations with gene expression.
The researchers evaluated protein expression was evaluated by immunohistochemistry on tissue microarrays.
|12 genes mapping at 20p11 were significantly overexpressed |
|Annals of Internal Medicine|
Patients with hepatic metastases were significantly more often male, more often had abnormal lactate dehydrogenase activity, exhibited primary tumor localization in the colon, and had synchronous onset of metastases.
With the findings and outcome fo the study the team found that the primary tumors of patients with hepatic metastases were more commonly T3 tumors, and less commonly of mucinous histology.
Gain of 20p11 was more often observed in patients with hepatic metastases, which was confirmed in an independent dataset.
The researchers found that 12 genes mapping at 20p11 were significantly overexpressed as a consequence of 20p11 copy number gain.
C20orf3 showed the strongest correlation between RNA expression and DNA copy number.
This was reflected in significantly higher protein expression in patients with hepatic metastases than in those with extrahepatic metastases.
Dr Mekenkamp's team concludes "C20orf3 mapping at 20p11 is associated with hepatic-specific metastasis in patients with colorectal cancer."
"This gene is a candidate biomarker for liver metastases and may be of clinical value in early-stage colorectal cancer."