The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

Hansen, Torben Frøstrup; Jensen, Lars Henrik; Spindler, Karen Lise Garm; Lindebjerg, Jan; Brandslund, Ivan; Jakobsen, Anders

doi:10.1111/j.1463-1318.2010.02357.x

Cited by 8 publications

(7 citation statements)

References 14 publications

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“…A retrospective analysis by Pogue-Geile et al [ 100 ] revealed that stage II/III dMMR CRC patients significantly derived potential survival benefit from the addition of bevacizumab to standard FOLFOX (HR = 0.52; 95% CI = 0.29–0.94) in contrast to pMMR patients (HR = 1.03; 95% CI = 0.84–1.27). Hansen et al [ 101 ] suggested that CRC patients with dMMR tumors had higher serum VEGF-A levels than those with pMMR tumors. Additionally, adding bevacizumab to adjuvant chemotherapy induced a decrease in Treg percentages but not conventional T cells in the peripheral blood of mCRCs [ 101 ].…”

Section: Predictive Value Of Mmr Status In Crc Treatmentmentioning

confidence: 99%

“…Hansen et al [ 101 ] suggested that CRC patients with dMMR tumors had higher serum VEGF-A levels than those with pMMR tumors. Additionally, adding bevacizumab to adjuvant chemotherapy induced a decrease in Treg percentages but not conventional T cells in the peripheral blood of mCRCs [ 101 ]. Thus dMMR CRC patients might get significant clinical benefit from bevacizumab owing to their immunosuppressive microenvironment and high serum levels of VEGF-A.…”

Section: Predictive Value Of Mmr Status In Crc Treatmentmentioning

confidence: 99%

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Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Zhang

Gong

et al. 2016

IJERPH

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Colorectal cancer (CRC) represents the third most common type of cancer in developed countries and one of the leading causes of cancer deaths worldwide. Personalized management of CRC has gained increasing attention since there are large inter-individual variations in the prognosis and response to drugs used to treat CRC owing to molecular heterogeneity. Approximately 15% of CRCs are caused by deficient mismatch repair (dMMR) characterized by microsatellite instability (MSI) phenotype. The present review is aimed at highlighting the role of MMR status in informing prognosis and personalized treatment of CRC including adjuvant chemotherapy, targeted therapy, and immune checkpoint inhibitor therapy to guide the individualized therapy of CRC.

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Section: Predictive Value Of Mmr Status In Crc Treatmentmentioning

confidence: 99%

Section: Predictive Value Of Mmr Status In Crc Treatmentmentioning

confidence: 99%

Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Zhang

Gong

et al. 2016

IJERPH

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“…However, other studies could not validate these findings ( Sinicrope et al , 2011 ). It has been suggested that the effects of anti-VEGF would also vary according to MSI status ( Hansen et al , 2011 ; Kloor et al , 2014 ).…”

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confidence: 99%

Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis

et al. 2015

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Background:Microsatellite instability (MSI) accounts for 15% of all colorectal tumours. Several specific clinicopathologicals (e.g., preference for the proximal colon over the distal colon, improved prognosis and altered response to chemotherapeutics) are described for this subset of tumours. This study aimed to analyse morphological, inflammatory and angiogenic features of MSI vs microsatellite stable (MSS) tumours.Methods:Twenty-seven MSS and 29 MSI, TNM stage matched, colorectal tumours were selected from the archive of the Department of Pathology, UZ Leuven. Morphology was analysed on haematoxylin–eosin sections. Immunohistochemistry for CD3, CD4, CD8, CD20 and CD68 was used to map tumour infiltration in both a digital and traditional microscope-based manner for all distinct morphological components of the tumour. CD31 immunostains were performed to assess angiogenesis.Results:Morphological tumour heterogeneity was a marked feature of MSI tumours, occurring in 53% of the cases as compared with 11% of the MSS tumours (P<0.001). Digital immune quantification showed an increased number of tumour-infiltrating cytotoxic T-lymphocytes (CD8+) in MSI compared with MSS tumours for both the tumour (P=0.02) and peritumoural area (P=0.03). Traditional microscope-based quantification confirmed these results (P<0.001 for both) and, in addition, revealed large numbers of CD68+ macrophages in the peritumoural area of MSI cancers (P=0.001). Moreover, traditional microscope-based analysis was able to distinguish between lymphocytes directly infiltrating the tumoural glands (intra-epithelial) and those infiltrating only the neoplastic stroma around the glands (intratumoural). Quantification showed high numbers of intra-epithelial CD3+, CD4+, CD8+, CD20+ and CD68+ cells in MSI compared with MSS cancers (P<0.001, P=0.01, P<0.001, P<0.001 and P=0.006, respectively). Higher microvessel density (MVD) was observed in MSI tumours compared with their MSS counterpart.Conclusions:Mixed morphology, reflecting tumour heterogeneity, is an important feature of MSI tumours and may have both diagnostic and therapeutic impact. The inflammatory reaction also presented with significant differences in MSI vs MSS colorectal tumours. MSI cancers showed mainly infiltration by cytotoxic T-cells in both the tumour and the close border around the tumour, as well as increased intra-epithelial infiltration in contrast to MSS tumours. The type of immune cell and the compartment it resides in (intratumoural or intra-epithelial) depend both on MSI status and morphology. Finally, MSI tumours showed a higher angiogenic capacity represented by an increased MVD, hinting for possible therapeutic consequences.

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“…There is evidence to suggest that a compensatory mechanism of VEGF-B/VEGFR1 signaling is involved in therapy resistance and anti-VEGF-A treatment [25,26]. It has also been shown that mCRC patients with MSI-H have higher levels of serum VEGF-A [45], that MSI-H tumors have increased angiogenic capacity [46], and that the presence of MSI could influence the effect of anti-VEGF-A therapies [47]. We wanted to investigate whether the clinical effects of the inhibition of VEGF signaling via B could be attributed to the instability of the VEGF-B gene.…”

Section: Discussionmentioning

confidence: 99%

Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients

Pirini

Pasini

Tedaldi

et al. 2020

IJMS

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Very few data are reported in the literature on the association between elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) and prognosis in advanced colorectal cancer. Moreover, there is no information available in relation to the response to antiangiogenic treatment. We analyzed EMAST and vascular endothelial growth factor-B (VEGF-B) microsatellite status, together with standard microsatellite instability (MSI), in relation to prognosis in 141 patients with metastatic colorectal cancer (mCRC) treated with chemotherapy (CT) alone (n = 51) or chemotherapy with bevacizumab (B) (CT + B; n = 90). High MSI (MSI-H) was detected in 3% of patients and was associated with progression-free survival (PFS; p = 0.005) and overall survival (OS; p < 0.0001). A total of 8% of cases showed EMAST instability, which was associated with worse PFS (p = 0.0006) and OS (p < 0.0001) in patients treated with CT + B. A total of 24.2% of patients showed VEGF-B instability associated with poorer outcome in (p = 0.005) in the CT arm. In conclusion, our analysis indicated that EMAST instability is associated with worse prognosis, particularly evident in patients receiving CT + B.

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The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

Abstract: This study provides some evidence to suggest that patients with an MSI tumour have higher serum VEGF-A levels than patients with an MSS tumour. If further validated, these findings could be of importance when considering the effects of anti-VEGF-A treatment.

Cited by 8 publications

References 14 publications

Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Role of Deficient Mismatch Repair in the Personalized Management of Colorectal Cancer

Microsatellite instable vs stable colon carcinomas: analysis of tumour heterogeneity, inflammation and angiogenesis

Instability of Non-Standard Microsatellites in Relation to Prognosis in Metastatic Colorectal Cancer Patients

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