Histological growth patterns of colorectal cancer liver metastases: a strong prognostic marker associated with invasive patterns of the primary tumor and p53 alteration

The histological growth pattern of liver metastases (desmoplastic, pushing, and replacement patterns) at the tumor-liver parenchymal interface is a prognostic factor in patients with colorectal cancer. However, data regarding its association with the primary tumor characteristics and molecular alterations are limited. This study evaluated the histological growth pattern in 136 cases of colorectal cancer liver metastases without preoperative treatment, comparing it with the clinicopathological features of the primary tumor. Liver metastasis exhibiting predominantly non-desmoplastic pattern (<50%), observed in 74 cases (54%), was associated with hepatic vein invasion (P = 0.025), worse recurrence-free survival (P < 0.001) and overall survival (P = 0.008). In multivariate analyses, multiple tumors (P < 0.001) and non-desmoplastic patterns (P = 0.009) were associated with worse recurrence-free survival, and tumor size (P = 0.025) and non-desmoplastic pattern (P = 0.025) were associated with worse overall survival. In 88 patients with available primary tumor tissue slides, non-desmoplastic pattern in the liver metastasis was associated with high-grade tumor budding (P = 0.002), high-grade poorly differentiated cluster (P = 0.021), absence of mucinous histology (P = 0.016), and aberrant p53 expression (complete loss or overexpression; P 0.001) of the primary colorectal cancer. In conclusion, the histological growth pattern in liver metastasis was a strong and independent prognostic factor for colorectal cancer. Our observations highlight the significant associations between histological growth patterns in liver metastases and histopathological features of the primary tumor, especially invasive front morphology and p53 aberration.