Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant...

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• The tumor microenvironment, characterized by proteolytic activity and inflammation, significantly influences cancer progression, particularly in colorectal cancer (CRC) liver metastases.
• Distinct immune profiles and proteolytic activity, indicated by urokinase-type plasminogen activator (uPAR) expression, are observed in CRC liver metastases.

Purpose of the Study:

• To investigate the expression of uPAR and the density of macrophages (CD68) and T cells (CD3) in resected CRC liver metastases.
• To correlate these markers with specific growth patterns (GP) of liver metastases (desmoplastic, pushing, replacement) in patients treated with neoadjuvant chemotherapy, with or without bevacizumab, compared to chemonaive patients.

Main Methods:

• Analysis of uPAR expression and CD68 (macrophage) and CD3 (T cell) density in liver metastases from CRC patients.
• Comparison of marker expression across different growth patterns (desmoplastic, pushing, replacement) in untreated, chemotherapy-treated, and chemotherapy plus bevacizumab-treated patient groups.

Main Results:

• In chemonaive patients, higher uPAR levels were found in desmoplastic metastases compared to pushing or replacement GPs. Higher CD68 density was observed in replacement GP metastases versus pushing GP.
• In chemotherapy-treated patients, CD68 density was higher in desmoplastic GP metastases than in pushing GP.
• In bevacizumab-treated patients, lower CD3 expression was noted in mixed GP metastases compared to desmoplastic or pushing GPs. uPAR and macrophage density differed between GPs in untreated patients.

Conclusions:

• Proteolysis and inflammation markers (uPAR, CD68, CD3) show differential expression related to liver metastasis growth patterns and neoadjuvant therapy, including bevacizumab. These findings suggest therapy-induced changes in the tumor microenvironment.
• While specific correlations between immune markers and growth patterns were not consistently demonstrated across all treatment groups, the study highlights the complex interplay between proteolysis, inflammation, tumor growth, and treatment response in CRC liver metastases.