BJMO - volume 17, issue 4, june 2023
L. Hendrickx MD, L. Van Mileghem MD, P. Vermeulen MD, L. Dirix MD
Cancer is a leading cause of morbidity and mortality worldwide. The process of metastasis involves many steps, with circulating tumour cells (CTCs) playing an essential role. This literature review examines the role of neutrophil extracellular traps (NETs) in the survival and implantation of CTCs in secondary organs. CTCs get to secondary organs primarily through the bloodstream and can then extravasate into the parenchyma of these organs. NETs are formed by various stimuli, including cancer. They can occur in primary tumours, but are most commonly present in metastatic tumour sites. They make the blood vessels of both primary organs and secondary organs more permeable, allowing CTCs to enter the bloodstream and extravasate from the bloodstream into the secondary organs, respectively. NETs also protect CTCs from degradation by the immune system and can trap CTCs in the microvasculature of secondary organs, allowing CTCs to be more numerous in the vasculature before entering these organs. This contributes to the formation of micrometastases and, subsequently, macrometastases. It also appears that this metastatic cascade is more easily initiated after surgery of the primary tumour, due to an increase in inflammation and, thus, increased formation of NETs. NETs can also awaken dormant tumour cells, which promotes metastasis as well. In short, NETs play an important role in the different stages of the life cycle of CTCs. Treatments against NETs may, therefore, offer important advances in fighting cancer.
(BELG J MED ONCOL 2023;17(4):112–7)Read more
BJMO - volume 17, issue 3, may 2023
L. Van Mileghem MD, L. Hendrickx MD, W. Seuntjens MD, P. Vermeulen MD, L. Dirix MD
The main cause of death in patients with breast cancer is the spread and outgrowth of tumour cells at distant sites. The presence of disseminated tumour cells (DTCs) in the bone marrow at diagnosis is a predictor for metastasis. This is an updated analysis of a prospective study in 100 patients with operable breast cancer on the long term-significance of bone marrow micrometastasis. The follow-up time ranges between one and 242 months, with a mean of 131 months and a median of 141 months. Bone marrow aspirates were analysed for the presence of DTCs by real-time polymerase chain reaction (RT-PCR) for cytokeratin 19 (CK19) and mammaglobin (MAM), as well as immunocytochemistry (ICC) for cytokeratin (CK). The aim of this study was to confirm the association between DTCs and disease-specific survival (DSS), as well as distant metastasis-free survival (DMFS).
CK19 positivity did not reach statistical significance for DSS (p=0.065) or DMFS (p=0.233). However, MAM positivity was significantly prognostic for DSS (HR: 5.583, p<0.001), but only borderline trending for DMFS (p=0.064). The combination of CK19 and MAM positivity, however, did confer a significantly increased risk for both DSS (HR: 3.073, p=0.003) and DMFS (HR: 3.150, p=0.023). ICC CK positivity significantly predicted DSS (HR: 3.868, p=0.040) or DMFS (HR: 3.868, p=0.040) when using a cut-off of ≥1 DTC. Stratifying the quantitative data also gave a significant result for DSS and DMFS (OR: 2.974, p=0.008). Combining both detection measurements using a cut-off of ≥1 DTC in immunochemical detection showed a significant association with DSS (HR: 3.213, p=0.089) and DMFS (HR: 4.984, p=0.015). Three negative parameters significantly predicted DSS (HR: 0.368, p= 0.017), but not DMFS. There was no statistically significant association of DTCs with organ-specific metastasis. This study supports the role of DTCs as a negative, prognostic factor in patients with operable breast cancer. The combination of multiple DTCs could be useful in identifying this increased risk.
(BELG J MED ONCOL 2023;17(3):71–84)Read more
BJMO - 2017, issue 3, february 2017
P-J. Van Dam MD, B. Galjart , P. De Paepe MD, PhD, T. Feryn , V. Duwel , L. Dirix MD, P. Vermeulen MD, S. Van Laere PhD
BJMO - 2017, issue 3, february 2017
A. Brouwer , P-J. Van Dam MD, E. Sluydts , M. Peeters MD, PhD, P. Vermeulen MD, S. Van Laere PhD, L. Dirix MD
BJMO - volume 6, issue 6, december 2012
M. Marsan , P. Neven MD, PhD, P. Vermeulen MD, L. Dirix MD, S. Van Laere PhD
TGF-β is a major regulator and driver of many biological processes, but its main function is inhibition of cell cycle progression and apoptosis, thus establishing a tumour-protective effect in early stages of malignant transformation. However, mutational alterations can occur at different levels of the TGF-β signaling cascade. These mutations, combined with the significant influence of the tumour microenvironment on this cascade, can cause a functional shift of TGF-β from being a tumour suppressor to becoming a tumour promoter in more advanced cancers. In most tumours this will ultimately contribute to the formation of metastatic laesions. In the clinical setting of breast cancer, TGF-β plays a significant role in the acquisition of endocrine resistance. Thus, therapeutic intervention of TGF-β signaling might deliver significant benefits in the treatment of cancer. (BELG J MED ONCOL 2012;6:188–193)Read more