The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

Forker, Laura; Gaunt, Piers; Sioletic, Stefano; Shenjere, Patrick; Potter, R. C.; Roberts, D. F.; Irlam, Joely J.; Valentine, Helen; Hughes, David J.; Hughes, Ana; Billingham, Lucinda; Grimer, R. J.; Seddon, Beatrice; Choudhury, Ananya; Robinson, Martin; West, Catharine M L

doi:10.1038/bjc.2017.430

Cited by 20 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The difference of the results reported in this manuscript might be attributed to a variety of factors such as the use of different antigen retrieval techniques and the use of a different primary antibody. Forker et al 36 investigated a selection of hypoxia markers, including CAIX, in a large cohort of soft tissue sarcomas. The cohort also contained 52 myxofibrosarcomas but the CA-IX expression was only reported for all STS types together.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).Myxofibrosarcoma (MFS) is a histological subtype of soft tissue sarcoma (STS) formerly classified as a myxoidtype malignant fibrous histiocytoma. It has been reclassified and defined as a distinct pathological entity in the World Health Organization (WHO) criteria set in 2002 1,2 . Myxofibrosarcoma is a relatively common sarcoma in the elderly that mainly arises in the extremities 3 . Primary MFS most often presents as a subcutaneous painless, slow growing nodule, but completely infiltrative growth patterns along fascial planes without formation of an evident tumor mass have also been described 4 . The low-grade lesions have a relatively low metastatic potential but show a significant propensity for local recurrences 5-8 . These recurrences show higher-grade histology in up to 50% of all cases compared to the primary tumor 3 . Subsequently, high and intermediate grade disease exhibits a greater metastatic potential, mainly metastasizing to the lungs and lymph nodes 7,9 . Current guidelines recommend wide surgical resection combined with pre or post-operative radiotherapy as the preferred treatment 10 . Despite this strategy, positive margins after surgery occur in up to 20% of cases and reported local relapse rates range from 15 to 65% [5][6][7][8]11 .Currently clinicians rely on conventional imaging modalities such as CT and MRI to determine the location and extent of tumor burden prior to surgery. Translating these conventional imaging modalities to the surgical theatre remains challenging, forcing the surgeon to depend mainly on tactile and visual cues during the procedure. P...

show abstract

Section: Discussionmentioning

confidence: 99%

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Gooyer

Versleijen-Jonkers²,

Hillebrandt-Roeffen³

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Despite recent progress in the identification of molecular and genetic alterations in STS 2 , 21 , 22 , routine prognostic risk assessment of STS patients still relies on the traditional model. These traditional prognostic factors have yet to be improved by the incorporation of novel biomarkers, which might be beneficial for individualized treatment.…”

Section: Discussionmentioning

confidence: 99%

Combined Use of the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios as a Prognostic Predictor in Patients with Operable Soft Tissue Sarcoma

Liang

Wang

et al. 2018

J. Cancer

View full text Add to dashboard Cite

Background: Preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with poor prognosis in soft tissue sarcoma (STS). The aim of the present study is to determine whether the combination of NLR and PLR (CNP) can better predict patient survival after resection for STS.Methods: We included 310 STS patients in this retrospective study. Preoperative CNP was calculated as follows: patients with both elevated NLR (>2.51) and PLR (>191.1) were given a score of 2; patients showing an increase in one or neither were allocated a score of 1 or 0, respectively.Results: Cut-off values of 2.51 and 191.1 were defined as elevated NLR and PLR, respectively. Elevated CNP was significantly associated with older age (P=0.034), larger tumor size (P=0.025), deeper tumor location (P=0.044), higher tumor grade (P=0.028), a more advanced stage according to the American Joint Committee on Cancer (AJCC) (P=0.005), shorter overall survival (OS) (P=0.000) and shorter disease-free survival (DFS) (P=0.000). Multivariate analysis indicated CNP but not NLR or PLR to be an independent prognostic factor for OS and DFS (P=0.000 and P=0.001, respectively).Conclusions: Preoperative CNP is associated with tumor progression and can be considered an independent marker of postoperative survival in patients with STS.

show abstract

“…Since the membrane localization of CA-IX, this enzyme plays a pivotal role in the regulation of pHi and pHe. Indeed, CA-IX is normally expressed in gut epithelial cells [9], but it is upregulated in many solid tumors including breast and lung [10][11][12][13]. Its expression is under control of the hypoxia inducible factor-1α (HIF-1α) and it is localized in chronically hypoxic tumor regions.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness

Ciccone

Filippelli

Angeli

et al. 2020

IJMS

View full text Add to dashboard Cite

Carbonic anhydrase IX (CA-IX) plays a pivotal role in regulation of pH in tumor milieu catalyzing carbonic acid formation by hydrating CO2. An acidification of tumor microenvironment contributes to tumor progression via multiple processes, including reduced cell-cell adhesion, increased migration and matrix invasion. We aimed to assess whether the pharmacological inhibition of CA-IX could impair tumor cell proliferation and invasion. Tumor epithelial cells from breast (MDA-MB-231) and lung (A549) cancer were used to evaluate the cytotoxic effect of sulfonamide CA-IX inhibitors. Two CA-IX enzyme blockers were tested, SLC-0111 (at present in phase Ib clinical trial) and AA-06-05. In these cells, the drugs inhibited cell proliferation, migration and invasion through shifting of the mesenchymal phenotype toward an epithelial one and by impairing matrix metalloprotease-2 (MMP-2) activity. The antitumor activity was elicited via apoptosis pathway activation. An upregulation of p53 was observed, which in turn regulated the activation of caspase-3. Inhibition of proteolytic activity was accompanied by upregulation of the endogenous tissue inhibitor TIMP-2. Collectively, these data confirm the potential use of CA-IX inhibitors, and in particular SLC-0111 and AA-06-05, as agents to be further developed, alone or in combination with other conventional anticancer drugs.

show abstract

The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma

Cited by 20 publications

References 26 publications

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma

Combined Use of the Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios as a Prognostic Predictor in Patients with Operable Soft Tissue Sarcoma

Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness

Contact Info

Product

Resources

About