Cancer Cell Biology

Breast Cancer Pathology Research

Professor I Ellis, Dr A Green, Dr D Powe and Dr E Rakha

The Breast Cancer Pathology Research Group is part of the large multidisciplinary Nottingham Breast Cancer Research Group. We have a longstanding research interest and international track record in classification of breast cancer, diagnosis and development of breast disease, evaluation of prognostic and predictive factors in breast cancer and studying mechanisms governing hormone response in breast cancer.

These include the Nottingham histological grading system, which has become the international gold standard for histological classification (WHO, UICC, EU and UK). The Nottingham Prognostic Index, also developed by the group, is regarded as the most effective system for clinical decision support in routine clinical management. Recently, it has been recognised that breast cancer develops as a consequence of a number of different specific molecular alterations, recognisable by molecular genetic and proteomic techniques, which manifest themselves as distinct and clinically relevant subgroups. We are now exploring the hypothesis that a novel classification of breast cancer based on phenotypic and molecular genetic characteristics will provide a more robust system for classification and therapeutic decision-making. As a consequence modern classification of breast cancer should be based on combined morphological, phenotypic (protein expression) and molecular genetic characteristics. This will provide a more robust system for classification and therapeutic decision-making and allow identification of novel therapeutic targets.

This work is being carried out in collaboration with John Roberston, KL Cheung & Caroline Chapman (Division of Breast Surgery) David Heery & Anne Willis (School of Pharmacy, University of Nottingham), Jon Garibaldi (School of Computational Sciences, University of Nottingham, Bob Reece & Graham Ball (Nottingham Trent University), Carlos Caldas (Cambridge University), Sarah Pinder (Guy’s Hospital), Jorge Reis-Filho (Breakthrough Breast Cancer), Rob Nicholson & Julia Gee (Tenovus Institute, Cardiff), Bill Gullick (Canterbury University), Val Speirs (University of Leeds). These studies involve use of tissue microarray technology (incorporating one of the largest well characterised tumour series that has been treated uniformly in a single institution, with a long term-follow-up and all clinical and therapeutic data),which allows biomarker screening in large numbers of cases and molecular genetic analysis of specific lesions with a pure histological morphology using MAPH, gene microarray, laser microdissection, fluorescent and colorimetric in situ hybridisation, comparative genomic hybridisation (CGH), quantitative PCR and proteomic analysis.

Cervical Cancer Screening

Dr R Seth

There is sufficient evidence indicating that cervical cancer and pre-cancer is caused by persistent infection with a high-risk human papillomavirus (HPV). Within the Department of Pathology at Queens Medical Centre, we are conducting a large, pragmatic, randomised controlled trial called - TOMBOLA trial. It stands for Trial Of Management of Borderline and Other Low-grade Abnormalities and one of its objectives is to identify the role of HPV testing as part of National Cervical Screening Programme.

It is a 3-centre trial (Nottingham, Aberdeen and Dundee) funded jointly by the MRC and the NHSCSP, and costs £4.2m conducted over 7 years. Over 5000 women have been recruited into the trial. All the HPV testing is being carried out in the Molecular Pathology Laboratory, at QMC.  Other biomarkers are also being studied using immunochemical and molecular biological techniques using clinical histological material from women with low-grade cervical disease to identify progression from low to high-grade cancer.

Pathways to diagnosis in child CNS tumours (CBTR)

Information about this topic will be available shortly.

Ovarian Cancer

Professor I Scott, Professor I Ellis, Professor L Durrant and Dr I Spendlove.

The newly established Ovarian Cancer Pathology group which aims to use the excellent breast cancer paradigm to provide a more robust modern classification of ovarian cancer by combining morphological and protein expression patterns. Prof Scott has carefully monitored a group of over 400 ovarian cancer patients from diagnosis through treatment to outcome. This information has been accurately recorded on a database. The tumours from these patients will now be incorporated into tissue microarrays to allow rapid screening of known and novel proteins that may aid in therapeutic decision making. A key to the success of this approach is the production of monoclonal antibodies that recognise denatured proteins on fixed tumour sections. Many antibodies only recognise native proteins and can be used on frozen but not fixed sections. Prof Durrant's group have 20 years experience in the production of monoclonal antibodies recognising both native and denatured cancer proteins.

Clinical Oncology website

Colorectal

Professor J Scholefield, Professor I Ellis, Professor L Durrant and Dr I Spendlove.

The newly established Colorectal Cancer Pathology group which aims to use the excellent breast cancer paradigm to provide a more robust modern classification of colorectal cancer by combining morphological and protein expression patterns. As part of the MRC population screening trial for colorectal cancer, Prof Scholefield has carefully monitored a group of over 2,000 colorectal  cancer patients from diagnosis through treatment to outcome. This information has been accurately recorded on a database. The tumours from these patients will now be incorporated into tissue microarrays to allow rapid screening of known and novel proteins that may aid in therapeutic decision making. A key to the success of this approach is the production of monoclonal antibodies that recognise denatured proteins on fixed tumour sections. Many antibodies only recognise native proteins and can be used on frozen but not fixed sections. Prof Durrant's group have 20 years experience in the production of monoclonal antibodies recognising both native and denatured cancer proteins.

Department of Surgery website

Clinical Oncology website

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