Site-Dependent Differences in Clinical, Pathohistological, and Molecular Parameters in Metastatic Colon Cancer

Abstract

The purpose was to develop a metastatic score specific to the hepatic and peritoneal site in colorectal cancer patients from clinical, pathohistological and molecular markers potentially reflecting oncogenic activation (OA) or epithelial-mesenchymal transition (EMT), where OA may reflect an activation and EMT the functional loss of certain genes. The primary tumour stage (OA, EMT), lymphonodal stage (OA), the presence of a lymphangiosis carcinomatosa (OA), histological grade (OA, EMT), and immunoblot extraction of E-cadherin (OA, EMT) were differentially rated with zero to one or two points due to their potential contribution to each process and the resulting scores were validated in 27 colorectal cancer patients (three patients with pre-malignant adenomas, 16 with primaries and two with local recurrencies, three of which were metastatic to the peritoneum, six metastatic to the liver and two metastatic to both, the liver and the peritoneum, and five with hepatic secondaries, one of which at histology was metastatic to the peritoneum too). As a single parameter only the N-stage significantly contributed to OA (p<0.05). Median OA and EMT scores, however, were 3.5 and 2 in the case of primaries without further spread, 5 and 4 in those nodal positive, 5 and 4 in the case of peritoneal implants, 6 and 2 in the case of liver metastases, and 6.5 and 3 in the case of a simultaneous hepatic and peritoneal spread, respectively. These differences were significant when scores from patients with and without liver metastases (OA, p<0.002) or with peritoneal implants and isolated hepatic spread (EMT, p<0.01) were compared. The results suggest a site-specific contribution of OA and EMT to tumour progression in human colon cancer.