Applications of cost-effective spectral imaging microscopy in cancer research

Barber, Paul R.; Vojnovic, B.; Atkin, Gary; Daley, Frances; Everett, Steven A.; Wilson, George; Gilbey, Julian

doi:10.1088/0022-3727/36/14/312

Cited by 22 publications

(16 citation statements)

References 14 publications

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“…For every scan session, separate background images were recorded. To extract and separate the color information from the diaminobenzidine and hematoxylin signals, the red, green, blue linear unmixing module in the TRI2 software (Apple Inc.) was applied using the absorption mode (20). For this procedure, reference files from single-stained control sections were used containing color information for the blue (hematoxylin; all nuclei) and brown (proliferating nuclei) signal.…”

Section: Immunohistochemical Image Acquisition and Image Processingmentioning

confidence: 99%

Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

Troost¹,

Bussink²,

Slootweg³

et al. 2010

J Nucl Med

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Accelerated tumor cell repopulation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. The noninvasive assessment of the proliferative state of a tumor by PET may provide a selection tool for customized treatment. 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of 18 F-FLT PET for tumor characterization is accepted and introduced into clinical studies, validation against tumor histology is mandatory. The aim of this study was to validate 18 F-FLT PET in squamous cell carcinomas of the oral cavity using immunohistochemical staining for the proliferation marker iododeoxyuridine and for TK-1. Methods: Seventeen patients with primary squamous cell carcinomas of the oral cavity underwent an 18 F-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. 18 F-FLT PET/CT scans were segmented, and PET/CT volumes and PET signal intensities were calculated (mean standardized uptake value [SUV mean ] and maximum standardized uptake value [SUV max ]). Multiple paraffin-embedded tumor sections were immunohistochemically stained for iododeoxyuridine and TK-1. For iododeoxyuridine, labeling indices and optical densities were calculated and correlated with SUV mean and SUV max . TK-1 staining was visually and semiquantitatively assessed. Results: All primary tumors were identified with 18 F-FLT PET but with a large range in tracer uptake (mean SUV max , 5.9; range, 2.2-15.2). Also, there was a large variability in iododeoxyuridine labeling indices (mean, 0.09; range, 0.01-0.29) and optical densities (mean, 28.2; range, 12.6-37.8). The iododeoxyuridine optical densities correlated significantly with SUV mean and SUV max , but the labeling indices did not. In most tumors, TK-1 staining of varying intensity was present but correlated with neither iododeoxyuridine binding nor 18 F-FLT uptake. Conclusion: The current study demonstrated only a weak correlation between 18 F-FLT uptake and iododeoxyuridine staining intensity in oral cavity tumors. This weak correlation may be explained by differences in biomarker characteristics, resolution, and quantification methods.

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Section: Immunohistochemical Image Acquisition and Image Processingmentioning

confidence: 99%

Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

Troost¹,

Bussink²,

Slootweg³

et al. 2010

J Nucl Med

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“…Immunohistochemical staining of marker protein expression was quantified using a spectral imager developed and constructed in our Institute, as reported previously (Barber et al, 2003). This allowed accurate immunostain quantification, with stain intensity being expressed as optical density (OD) normalized to reference spectra.…”

Section: Quantification Of Marker Protein Expression By Spectral Imagingmentioning

confidence: 99%

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model

et al. 2005

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Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase -polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation.

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Section: Quantification Of Marker Protein Expressionmentioning

confidence: 99%

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

et al. 2006

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The goal of targeted therapy has driven a search for markers of prognosis and response to adjuvant therapy. The surgical resection of a solid tumour induces tissue ischaemia and acidosis, both potent mediators of gene expression. This study investigated the impact of colorectal cancer (CRC) surgery on prognostic and predictive marker levels. Tumour expression of thymidylate synthase, thymidine phosphorylase, cyclin A, vascular endothelial growth factor (VEGF), carbonic anhydrase-9, hypoxia inducible factor-1a, and glucose transporter-1 (GLUT-1) proteins was determined before and after rectal cancer surgery. Spectral imaging of tissue sections stained by immunohistochemistry provided quantitative data. Surgery altered thymidylate synthase protein expression (P ¼ 0.02), and this correlated with the change in the proliferation marker cyclin A. The expression of hypoxia inducible factor-1a, VEGF, and GLUT-1 proteins was also different following surgery. Colorectal cancer surgery significantly impacts on intratumoral gene expression, suggesting archival specimens may not accurately reflect in situ marker levels. Although rectal cancer was the studied model, the results may be applicable to any solid tumour undergoing extirpation in which molecular markers have been proposed to guide patient therapy.

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Applications of cost-effective spectral imaging microscopy in cancer research

Cited by 22 publications

References 14 publications

Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

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Applications of cost-effective spectral imaging microscopy in cancer research

Cited by 22 publications

References 14 publications

Histopathologic Validation of 3′-Deoxy-3′-18F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

Histopathologic Validation of 3′-Deoxy-3′-18F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model

The impact of surgically induced ischaemia on protein levels in patients undergoing rectal cancer surgery

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Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity

Histopathologic Validation of 3′-Deoxy-3′-¹⁸F-Fluorothymidine PET in Squamous Cell Carcinoma of the Oral Cavity