3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.

Background

Colorectal liver metastases (CLM) display a high heterogeneity, responsible for a wide array of clinical presentations and responsiveness to treatments. In the era of precision medicine, there is a critical need of reliable prognostic markers to improve patient stratification and, for their predominance in metastatic tissues, tumor-associated macrophages (TAMs) emerge as promising candidates. The aim of this study was to test the presence of discrete TAM populations in CLM patients on the basis of morphology, and to test the impact of TAMs morphology on recurrence-free survival (RFS).

Methods

NCT038888638 is a single-center study conducted in a tertiary-referral university hospital that examined a cohort of patients with CLMs that underwent hepatectomy between 2005 and 2017. TAMs cell density, cell area and cell perimeter were systematically quantified in 3 non-contiguous and non-overlapping areas of CLM sections by means of immuno-reactive area of CD163+ macrophages. The association of TAMs metrics and RFS was tested by using receiver operating characteristics (ROC) curves, multivariate Cox regression analysis and survival analysis.

Results

A cohort of 101 CLM patients resected between 2005 and 2017 was considered. Among density (AUC=0.555; 95%CI=0.410-0.701; P = 0.449), perimeter (AUC=0.526; 95%CI=0.383-0.671; P = 0.708) and area (AUC=0.791; 95%CI=0.572-0.841; P = 0.006) ofCD163+ TAMs, only the latter was significantly associated with differences in survival time. Small and large TAMs, as defined by using the best cutoff value extrapolated from the ROC curve (area: 60.39 μm²; Se = 0.79; Sp = 0.44), were clearly associated with significantly different 5-year RFS rates of 27.8% and 0.2% respectively (P < 0.001). At the multivariate analysis, including TAMs area and several prognostic factors, only TAMs area was found to be independently statistically associated with RFS (HR = 3.41; 95%CI=1.13-5.43; P = 0.001).

Conclusions

Macrophage morphology is critically associated with prognosis of CLM patients. The results reported here support that accurate quantitative morphometric characterization of TAMs can serve as an easily quantifiable correlate of functional diversity with prognostic significance.

Clinical trial identification

NCT038888638.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

All authors have declared no conflicts of interest.