Histopathological growth pattern of liver metastases as an independent marker of metastatic behavior in different primary cancers

Ali Bohlok; François Richard; Valerio Lucidi; Antoine El Asmar; Pieter Demetter; Ligia Craciun; Denis Larsimont; Alain Hendlisz; Jean Luc Van Laethem; Luc Dirix; Christine Desmedt; Peter Vermeulen; Vincent Donckier

doi:10.3389/fonc.2023.1260880

Histopathological growth pattern of liver metastases as an independent marker of metastatic behavior in different primary cancers

Front Oncol. 2023 Oct 27:13:1260880. doi: 10.3389/fonc.2023.1260880. eCollection 2023.

Authors

Affiliations

¹ Surgical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
² Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium.
³ Abdominal Surgery, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
⁴ Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
⁵ Digestive Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
⁶ Hepatogastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
⁷ Translational Cancer Research Unit, Gasthuiszusters Antwerp Hospitals and University of Antwerp, Antwerp, Belgium.

^# Contributed equally.

Abstract

Surgical resection can lead to prolonged survival in patients with isolated liver metastases (LM) from various primary cancers. However, there are currently no validated predictive markers to discriminate between these oligo/argometastatic patients, who will benefit from surgery, and those with diffuse metastatic behavior in whom surgery will be futile. To evaluate whether the tumor microenvironment, or histopathological growth pattern (HGP), of LM reflects the type of metastatic progression independently of the origin of the primary cancer, we analyzed a combined series of patients who underwent surgery for colorectal LM (N=263) or non-colorectal LM (N=66). HGPs of LM were scored in each patient to distinguish between desmoplastic HGP (all LM showing a complete encapsulated pattern) and non-desmoplastic HGP (at least one LM with some infiltrating-replacement component). In the entire series, 5-year overall and progression-free survival were, 44.5% and 15.5%, respectively, with no significant differences between colorectal and non-colorectal LM. In patients with desmoplastic HGP, 5-year overall and progression-free survival were 57% and 32%, respectively, as compared to 41% and 12%, respectively, in patients with non-desmoplastic-HGP (p=0.03 and 0.005). Irrespective of cancer origin and compared to traditional risk factors, desmoplastic HGP was the most significant predictor for better post-operative overall survival (adjusted HR: 0.62; 95% CI: [0.49-0.97]; p=0.035) and progression-free survival (adjusted HR: 0.61; 95% CI: [0.42-0.87], p=0.006). This suggests that the HGP of LM may represent an accurate marker that reflects the mode of metastatic behavior, independently of primary cancer type.

Keywords: histopathological growth pattern; liver; marker; metastases; prognostic.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work has been funded by” Les Amis de Bordet”, “Le Fond Ithier” and the Belgian Foundation against Cancer (C/2020/1441). François Richard is funded by The Research Foundation – Flanders. The funders of this study had no role in the design of the study, the collection, analysis and interpretation of the data, the writing of the manuscript, or the decision to submit for publication.