Steatosis shifts the histopathological heterogeneity of liver metastases towards poor prognosis replacement growth in colorectal cancer patients

Two distinct histological growth patterns characterize liver metastases: the desmoplastic growth pattern, marked by a stromal encapsulating ring around the metastasis, and the replacement growth pattern, where cancer cells integrate into and replace the native hepatocyte architecture. The replacement pattern is associated with poorer therapeutic responses and worse overall prognosis.

Concurrently, obesity, which alters the liver microenvironment, is linked to unfavorable outcomes in colorectal cancer patients. This study explores the interplay between a lipid-rich liver microenvironment and histological growth patterns in metastases. Using resected patient specimens and preclinical mouse models of obesity, we observed a correlation between liver steatosis and a shift toward the more aggressive replacement growth pattern.