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Cytometric detection of nuclear features associated with pre-malignancy or malignancy in human bronchial specimens

University of British Columbia

Approximately 600,000 people in the developed world die each year from lung cancer. The five year survival rate for lung cancer has remained at 13% for the past 30 years. Currently, Stage I Non Small Cell Lung Cancer five year survival rates have been reported at 76%, Stage II 25%,, Stage Ilia and Illb less than 7%, and with Stage IV, five year survival is rare. About 80% of lung cancers are not clinically detected until they are no longer localized. It is assumed that if more people had their lung cancers detected in Stage I rather than in more advanced stages, mortality would be reduced. The hypothesis was that the sensitivity of sputum cytology for detecting early lung cancers can be improved by exploiting the phenomenon of malignancy associated changes (MACs) by a quantitative measurement of changes in DNA distribution. In patients with lung cancer, it was demonstrated that in bronchial biopsies diagnosed as normal by conventional methods, MACs can be detected in approximately 86% of the biopsies. MAC value did not correlate with the distance from the tumour. This MAC expression returned to normal levels after tumour resection. In historical sputum samples it was possible to detect MACs in approximately 80% of the samples including those with no diagnostic cells by conventional criteria. These MACs were detected approximately one year or more before cancer was detected either clinically or by x-ray. MAC expression was shown to be independent of the number of acute inflammatory cells present in the sputum. It was further demonstrated that MACs decrease significantly after successful surgical resection, but persist in patients who develop a recurrence or metastasis within three years after surgery.

Thesis/Dissertation

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2009-04-20

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http://hdl.handle.net/2429/7430

Pathology

University of British Columbia

UBCV

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