G5 Article dissertation
Epidermal growth factor receptor and other tissue biomarkers in gastrointestinal cancers
Authors: Birkman Eva-Maria
Publisher: University of Turku
Publishing place: Turku
Publication year: 2019
ISBN: 978-951-29-7778-9
eISBN: 978-951-29-7779-6
Web address : http://urn.fi/URN:ISBN:978-951-29-7779-6
Self-archived copy’s web address: http://urn.fi/URN:ISBN:978-951-29-7779-6
Personalised medicine has plays an increasing role in the treatment of cancer. New therapeutic molecules are being developed, but their compatibility for each patient has to be tested before starting the treatment by examining the appropriate tissue biomarkers expressed in the tumour. These biomarkers can be utilised not only in treatment selection but also in predicting treatment efficacy and patient survival. They can also be used to classify tumours into specific molecular subtypes that have distinct characteristics related to tumour behaviour, response to cancer treatments and prognosis of the patients. In order to implement these classifications in clinical practice, instead of time-consuming sequencing-based methods, the methods have to be simple enough and easy to interpret.
Gastrointestinal cancers are among the most prevalent malignancies and often lead to death. Monoclonal antibodies against the epidermal growth factor receptor (EGFR) can be used in the treatment of RAS wild-type metastatic colorectal cancer. It has been shown that in addition to RAS mutation testing, determining the EGFR gene copy number (GCN) of the tumours can aid in selecting the patients likely to benefit from the antibody treatment. In oesophagogastric cancer, EGFR GCN has not yet been shown to have a predictive role, although the overexpression of HER2, which belongs to the same receptor family as EGFR, is used as a biomarker to predict response to anti-HER2 antibody treatment. In this thesis, the prevalence of EGFR amplification was observed to be at a similar level with the prevalence of HER2 amplification specifically among the intestinal-type oesophagogastric adenocarcinomas from 220 patients. This implies that it might be useful to examine whether EGFR GCN analysis could function as a biomarker predicting anti-EGFR treatment response in the intestinal-type tumours. In addition, in this thesis, tissue microarray was used to detect the different molecular subtypes of oesophagogastric cancers from 244 patients by staining methods applicable to clinical practice.
Comparative studies detecting EGFR GCN in primary colorectal tumours and their metastases are scarce. In this thesis, corresponding primary and metastatic tumours from 80 patients were examined. EGFR GCN was observed to decrease between the primary and metastatic tumours during anti-EGFR treatment but to remain stable or even increase among patients not receiving treated with anti-EGFR antibodies. This EGFR GCN change may be relevant regarding the clinical response to anti-EGFR treatment.
Preoperative chemoradiotherapy can be used in the treatment of rectal cancer patients to enable a complete resection of the tumour or reduce the risk of local recurrence. However, treatment response among patients is variable. Thus, a suitable biomarker could be helpful in predicting response or stratifying patients into separate treatment groups according to their prognosis. In this thesis, CIP2A expression was examined in rectal cancer tissue samples from 210 patients. Low CIP2A expression level was observed to associate with a better response among patients treated with long-course chemoradiotherapy. Affirming results were obtained in cell culture studies, where the suppression of CIP2A expression was observed to render the cells more sensitive to irradiation than the cells with normal CIP2A expression.