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Title: Biomarkers for the classification of high grade neuroendocrine lung cancers
Author: Bari, Muhammad Furqan
ISNI:       0000 0004 2748 771X
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2012
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In the management of lung cancer the most important step beyond establishing the presence a malignant tumour is identifying whether the tumour is small cell lung cancer (SCLC) or one of the variants of non-small cell carcinoma (NSCLC), which includes adenocarcinoma (AD), squamous (SCC), large cell carcinoma (LCC), large cell neuroendocrine carcinoma (LCNEC), typical carcinoids (TC) and atypical carcinoids (AT). SCLC is a high grade neuroendocrine tumour which usually presents as central mass. These tumours are not usually amenable to curative surgical resection and are treated primarily by chemotherapy resulting in a treatment dichotomy of SCLC and NSCLC. The diagnosis of the tumour subtypes is routinely established on cytology or histology samples and in case of AD, LCC and SCC, which are not neuroendocrine tumours, the diagnosis is aided by neuroendocrine markers. However for TC, AT and LCNEC which are neuroendocrine tumours, the diagnosis is based on morphological features alone, which in some cases overlap and result in difficulty in diagnosis. This inter-observer variability is common among the neuroendocrine lung tumours and is highest between SCLC and LCNEC followed by TC and AC. Currently no marker or ancillary stain are clinically in practice which can aid in classification of these neuroendocrine tumours. In an attempt to address this issue, this project evaluated the use of bioinformatics to analyze publicly available high through-put transcriptomic data to identify markers which would aid in the distinction of SCLC from LCNEC. However, the markers identified were found to have low specificity and sensitivity, leading to the conduction of a de novo gene expression study utilizing laser micro-dissection of pure tumour samples of SCLC and LCNEC. This experiment yielded a different set of top ranked discriminator genes of which validation at the protein level by immunocytochemistry supported CDX2, CD99 and CD44 as LCNEC specific markers and BAI3 as a SCLC specific marker.
Supervisor: Not available Sponsor: Higher Education Commission ; Pakistan ; Dow University of Health Sciences
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)