Journal: Journal of Pathology Informatics

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Publisher

Medknow Publications and Media

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ISSN

2229-5089

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  • Rupp, Niels J.; Schüffler, Peter J.; Zhong, Qing; et al. (2016)
    Journal of Pathology Informatics
    Background: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. Materials and Methods: To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia-related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot-assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia-related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia-related proteins. Results: Based on pimonidazole staining and other hypoxia-related proteins (osteopontin, hypoxia-inducible factor 1-alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia-related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer-based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue. Conclusions: This platform can be used for precise colocalization of novel candidate hypoxia-related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations
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