Professor Rebecca Fitzgerald
Our work focuses on the early detection and treatment of cancer of the oesophagus. Oesophageal cancers are the 8th most common cancer worldwide and the 6th most common cause of cancer death with only 15% surviving 5 years. The two main subtypes of oesophageal cancer: adenocarcinoma and squamous cell carcinoma (OSCC) have a remarkably improved survival when diagnosed at an early stage.
Most of our work to date has focussed on oesophageal adenocarcinoma which is the fifth most common cause of cancer death in England and Wales, accounting for over 7,000 deaths every year. Furthermore, this cancer has increased 6 fold in the western world in the past 20 years making it a public health concern. This disease develops slowly, at the oesophageal-gastric junction, from a condition called Barrett’s oesophagus. Barrett’s oesophagus is a metaplastic disorder in which the multilayered normal lining of the oesophagus is replaced with a single sheet of column-shaped cells, which are more similar to those found in the intestine. Approximately 1 in 200 patients with Barrett’s oesophagus will progress to adenocarcinoma per year.
Little is also known about the early development of Barrett’s oesophagus. The epidemiological evidence suggests that gastro-oesophageal reflux and obesity are the main risk factors but it is still unclear which specific cellular and molecular factors are involved in the development of the disease. Understanding the mechanisms behind the early development of Barrett’s could help to identify and improve prevention, diagnostic and therapeutic strategies.
A. Endoscopic views of Barrett's oesophagus. B. Histopathological oesophageal sections. Normal squamous oesophageal mucosa (top) undergoes intestinal metaplasia to result in a columnar segment showing rudimentary villi and glands with goblet cells (blue), (middle). In cancer (bottom), nuclear and tissue glandular architecture are disrupted.
Our main research aims are to:
- Understand how Barrett’s oesophagus develops and identify the cellular and molecular factors that induce or are involved in its onset. More information.
- Find new tools and specific biomarkers that will allow the diagnosis of the disease at an earlier stage and identify the patients who are at a higher risk of developing cancer. We are now extending these approaches to squamous cell carcinoma of the oesophagus. More information.
- Improve the outcome and management of cancer patients. More information.
Rebecca is interested in hearing from anyone with a clinical or scientific background interested in joining the laboratory or clinical infrastructure team at any time. Click here to contact Professor Rebecca Fitzgerald by email.
Other contacts: Dr Pierre Lao-Sirieix, Group Research Manager
Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis. Weaver JM, Ross-Innes CS, Shannon N, Lynch AG, Forshew T, Barbera M, Murtaza M, Ong CA, Lao-Sirieix P, Dunning MJ, Smith L, Smith ML, Anderson CL, Carvalho B, O'Donovan M, Underwood TJ, May AP, Grehan N, Hardwick R, Davies J, Oloumi A, Aparicio S, Caldas C, Eldridge MD, Edwards PA, Rosenfeld N, Tavaré S, Fitzgerald RC; OCCAMS Consortium; OCCAMS Consortium. Nat Genet. 2014 Aug;46(8):837-43. doi: 10.1038/ng.3013.
Amplification of TRIM44: pairing a prognostic target with potential therapeutic strategy. Ong CA, Shannon NB, Ross-Innes CS, O'Donovan M, Rueda OM, Hu DE, Kettunen MI, Walker CE, Noorani A, Hardwick RH, Caldas C, Brindle K, Fitzgerald RC. J Natl Cancer Inst. 2014 Apr 28;106(5). pii: dju050. doi: 10.1093/jnci/dju050.
Gastro-esophageal reflux disease symptoms and demographic factors as a pre-screening tool for Barrett's esophagus. Liu X, Wong A, Kadri SR, Corovic A, O'Donovan M, Lao-Sirieix P, Lovat LB, Burnham RW, Fitzgerald RC. PLoS One. 2014 Apr 15;9(4):e94163. doi: 10.1371/journal.pone.0094163. eCollection 2014.
Three-gene immunohistochemical panel adds to clinical staging algorithms to predict prognosis for patients with esophageal adenocarcinoma. Ong CA, Shapiro J, Nason KS, Davison JM, Liu X, Ross-Innes C, O'Donovan M, Dinjens WN, Biermann K, Shannon N, Worster S, Schulz LK, Luketich JD, Wijnhoven BP, Hardwick RH, Fitzgerald RC. J Clin Oncol. 2013 Apr 20;31(12):1576-82. doi: 10.1200/JCO.2012.45.9636.
Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus. Bird-Lieberman EL, Neves AA, Lao-Sirieix P, O’Donovan M, Novelli M, Lovat LB, Eng WS, Mahal LK, Brindle KM and Fitzgerald RC. Nat Med. 2012 Jan 15;18(2):315-21.
Integrative analysis of array-comparative genomic hybridisation and matched gene expression profiling data reveals novel genes with prognostic significance in oesophageal adenocarcinoma. Goh XY, Rees JR, Paterson AL, Chin SF, Marioni JC, Save V, O'Donovan M, Eijk PP, Alderson D, Ylstra B, Caldas C, Fitzgerald RC. Gut. 2011 Apr 12. CLICK HERE TO VIEW A FULL PDF OF THIS PAPER
Acceptability and accuracy of a non-endoscopic screening test for Barrett's oesophagus in primary care: cohort study. Kadri SR, Lao-Sirieix P, O'Donovan M, Debiram I, Das M, Blazeby JM, Emery J, Boussioutas A, Morris H, Walter FM, Pharoah P, Hardwick RH, Fitzgerald RC. BMJ. 2010 Sep 10;341:c4372. CLICK HERE TO VIEW A FULL PDF OF THIS PAPER
A 4-gene signature predicts survival of patients with resected adenocarcinoma of the esophagus, junction, and gastric cardia. Peters CJ, Rees JR, Hardwick RH, Hardwick JS, Vowler SL, Ong CA, Zhang C, Save V, O'Donovan M, Rassl D, Alderson D, Caldas C, Fitzgerald RC; Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Study Group. Gastroenterology. 2010 Dec;139(6):1995-2004.e15. CLICK HERE TO VIEW A FULL PDF OF THIS PAPER
Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Saadi A, Shannon NB, Lao-Sirieix P, O'Donovan M, Walker E, Clemons NJ, Hardwick JS, Zhang C, Das M, Save V, Novelli M, Balkwill F, Fitzgerald RC. Proc Natl Acad Sci USA. 2010 Feb 2;107(5):2177-82. CLICK HERE TO VIEW A FULL PDF OF THIS PAPER