Clinico‐metabolic characterization improves the prognostic value of histological growth patterns in patients undergoing surgery for colorectal liver metastases

Bohlok, Ali; Derijckere, Ivan Duran; Azema, Hugues; Lucidi, Valério; Vankerckhove, Sophie; Hendlisz, Alain; Laethem, Jean Luc Van; Vierasu, Irina; Goldman, Serge; Flamen, Patrick; Larsimont, Denis; Demetter, Pieter; Dirix, Luc; Vermeulen, Peter; Donckier, Vincent

doi:10.1002/jso.26466

Cited by 6 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of interest is that we observed that cancer cells from the rHGP display an intrinsic strong glycolytic profile, which is strongly associated with a more aggressive phenotype [ 50 , 51 ]. This observation is further supported by a previous report that a higher baseline glucose uptake of CRCLM was detected in non‐dHGP patients, when compared with dHGP patients [ 84 ]. Accordingly, the rHGP is associated with the activation of the PPP, which plays a role in antioxidant defence, thereby suggesting higher resistance to ROS in rHGP CRCLM.…”

Section: Discussionsupporting

confidence: 88%

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood. Methods We evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures. Results We detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis. Conclusion These findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO.

show abstract

Section: Discussionsupporting

confidence: 88%

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The desmoplastic pattern has angiogenic vascular hot spots in between cancer cell nests and hypoxic areas while the replacement growth pattern shows a uniformly high vessel density and minimal hypoxia, probably because of efficient vessel co-option [30,38,41]. Consequently, replacement-type liver metastases are also metabolically more active than desmoplastic liver metastases, as demonstrated by FDG-PET analyses [79].…”

Section: Discussionmentioning

confidence: 98%

“…Bohlok A J Surg Oncol, 2021 [79] The metabolic Clinical Risk Score (mCRS), which includes FDG-PET as a metabolic parameter, was compared with the HGP of liver metastases and the prognosƟc value of combining mCRS and HGP was assessed in 108 paƟents.…”

Section: Colorectal Cancermentioning

confidence: 99%

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights

et al. 2022

Self Cite

View full text Add to dashboard Cite

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.

show abstract

“…In parallel with HGPs, high preoperative glucose uptake representing high metabolism rate is associated with poor prognosis in CRCLM[ 21 , 22 ]. When integrating preoperative metabolic parameters with HGPs, the postoperative prognostic value could be improved[ 23 ]. As expected, similar results appeared in studies on correlation between HGPs and immunophenotype and genomic mutation[ 19 , 24 ].…”

Section: Prognostic Value Of Hgpsmentioning

confidence: 99%

Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases

Kong¹,

Fan²,

Wang³

et al. 2022

WJG

View full text Add to dashboard Cite

Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.

show abstract

Clinico‐metabolic characterization improves the prognostic value of histological growth patterns in patients undergoing surgery for colorectal liver metastases

Cited by 6 publications

References 50 publications

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights

Clinical implications and mechanism of histopathological growth pattern in colorectal cancer liver metastases

Contact Info

Product

Resources

About