Supplementary for Assessment of Microvessel Density and Tumor Proximity for Prognosis of Cancer

DESCRIPTION provided by applicant Tumor microenvironment TME makes an essential contribution to tumor progression recurrence and metastasis Currently there is no standardized method to quantify major components of TME simultaneously such as lymphovascular invasion and to predict locoregional recurrence and metastasis of cancer The primary goal of this project is to develop a technology for quantification of the TME signatures by using quantum dot QD based immunohistofluorescence IHF We expect that either single or multiplexed biomarkers for the TME components can be used to assess prognosis including risk of the locoregional recurrence and metastasis We have recently developed QD based IHF technology for quantification of multiplexed biomarkers Our preliminary study support us to accomplish the objective of this study that is to develop a molecular imaging technology for quantification of major signatures of TME as a tool for assessment of the prognosis and prediction of the recurrence and metastasis In this project we will focus on technique development using head and neck cancer HNC It is anticipated that using this technology HNC pathologists will be able to more accurately identify patients who are at high risk for poor prognosis This would provide valuable information to head and neck cancer surgeons radiation oncologist and medical oncologists to make appropriate treatment decisions This technology also has the potential to be applied to the treatment and care of other types of cancer with appropriate modifications The project will involve Specific Aims with measurable milestones Aim To prepare and validate QD antibody Ab conjugates which specifically recognize blood and lymphatic vasculatures and EGFR in formalin fixed and paraffin embedded FFPE cancer tissues Milestones for this aim are completion and optimization of QD Ab conjugates with high binding affinity and selectivity establishment of the quantification method for both density of the TME signatures and their distance to tumor nests validation of the QD based IHF by comparing this method with the conventional IHC Aim To examine whether microvessel density and tumor proximity can serve as a prognostic biomarkers and correlate them with locoregional recurrence and lymph node metastasis of HNC Milestones for this aim are completion of staining and quantification of the TME signatures using FFPE samples from HNC patients with and without lymph node metastasis and recurrent disease completion of statistical analysis to correlate microvessel density and tumor proximity with clinical characteristics of HNC patients PUBLIC HEALTH RELEVANCE The proposed project will develop a quantum dot based multiplexing technology to quantify tumor microenvironment with a focus on blood and lymphatic vasculatures which may help pathologists to accurately identify patients who are at high risk for poor prognosis We will use head and neck cancer for technology development but this technology can also be applied to prognosis of other cancers and provide valuable information to cancer surgeons radiation oncologists and medical oncologists to help them make appropriate treatment decisions