AbstractsBiology & Animal Science

Image analysis of prostate cancer tissue biomarkers

by Giuseppe Lippolis




Institution: University of Lund
Department:
Year: 2015
Keywords: image analysis; prostate cancer; Time Resolved Fluorescence; automated Gleason; PSA; AR; fusion gene; TMAs; Technology and Engineering; Biology and Life Sciences; Medicine and Health Sciences
Record ID: 1356591
Full text PDF: http://lup.lub.lu.se/record/5367942


http://lup.lub.lu.se/record/5367942/file/5367952.pdf


Abstract

Prostate cancer is the second most common cancer in men. In order to improve diagnosis and prognosis, new sensitive and specific biomarkers are needed. Tissue biomarkers carry expression and morphological information of the tissue where they are expressed. However their use is still limited by technological problems, lack of standardized procedures and inadequate interpretation. In this work we investigated a group of tissue biomarkers as well as new technologies and computerized approaches for consistent and reproducible analyses. We also tested an automated approach for performing Gleason grading. In order to validate previous in silico studies, we investigated the expression of ERG (as a surrogate marker of TMPRSS2:ERG gene fusion status) and TATI (encoded by SPINK1) proteins in a large TMA of localized prostate cancer patients. We observed a mutually exclusive expression pattern, further supporting the idea of tailored treatment for genotypically different cancers. In the second and third studies we introduce the use of image analysis for an integrated approach that uses Time Resolved Fluorescence Imaging on PSA and AR, immunofluorescence on cytokeratin as well as brightfield microscopy on H&E and p63/AMACR. The workflow includes the following automated steps: multi-modality image registration, identification of regions of interest, recognition of benign versus cancer areas and protein quantification. PSA seemed to decrease in cancer while AR increased in AMACR+ and decreased in AMACR- cancer tissue compared to benign. Finally, we developed a system based on SIFT features and BoW approach to automatically perform Gleason grading. The system was able to distinguish between grades with very high accuracy. Prostate cancer is one of the most common cancers in the world and the second most common in men. The western world has the highest incidence rates. The causes of prostate cancer are not yet clear, however a number of risk factors have been identified such as familial history, ethnicity, diet and genetic events. Prostate cancer affects primarily elderly men with the majority of the cases happening above 65 years of age. If caught at an early stage, prostate cancer is curable by removal of the whole prostate whereas advanced or recurrent disease is lethal and only palliative methods are available for patients. Nowadays the tools to diagnose the disease include PSA blood test and a rectal examination conducted by a pathologist to detect suspicious lumps. PSA is a protein produced by the prostate; when its amount goes up beyond a certain level, it may indicate cancer or other pathological conditions that are not life threatening. The only way to be sure that a patient harbours a tumour in the prostate, is to perform a biopsy (generally from multiple areas at once) and analyse it using a microscope. The problem with blood PSA test is that it unfortunately detects many false positives. This…