The behavior and prognosis of cancer is affected by several factors, including alterations in the cancer cells and changes in the tumor microenvironment.



The aim of the present study was to investigate new predictive and prognostic factors

located in the cancer cells (EGFR gene copy number, EGFR, oncogene pim-1) or tumor

microenvironment, including lymphatic vessels (CLEVER-1, podoplanin), macrophages

(CD68, CLEVER-1), and T-lymphocytes (CD3) in colorectal cancer. Furthermore,

the molecular characteristics of lymphatic vessels (CD73, LYVE-1, podoplanin)

as well as the lymphocyte and dendritic cell trafficking in lymphatics were studied.



The results indicate that high Pim-1 expression, a high number of CD68+ macrophages

peritumorally, and in early stage disease, a high number of CLEVER-1+ macrophages

and vessels peritumorally are factors associated with a favorable disease outcome in

colorectal cancer. In contrast, in stage IV disease, a high number of CLEVER-1+ macrophages both intra- and peritumorally are associated with poor survival. EGFR gene copy number measured by silver in situ hybridization predicts anti-EGFR treatment

response in metastatic colorectal cancer more accurately than the routinely used KRAS

analysis. In addition, lymphatic vessels exhibit marked phenotypic heterogeneity in

healthy and cancer tissues and the function of CD73 in lymphatics differs from blood

vessels as demonstrated in this study.



In summary, colorectal cancer prognosis is affected distinctly at different stages of

disease and varies depending on the location of lymphatic vessels and macrophages,

whereas a high Pim-1 expression is associated with a favorable survival. Moreover,

EGFR gene copy number is a promising new predictive marker in metastatic colorectal

cancer patients with wild type KRAS.