Project: Research project

Project Details


The aim of this study is to improve the molecular analysis of pre-
neoplastic and neoplastic tissue obtained by endoscopic biopsy. The long-
term goal of this study is to develop a method of performing molecular
analysis of lesions from which only limited sized specimens can be
sampled. Endoscopic biopsies are routinely obtained from gastrointestinal
neoplasms but two major problems have prevented their utilization for
molecular analysis. The primary problem with existing technology has been
the need to rely solely on visual inspection to determine which tissue can
be used for molecular analysis. The second is the inability to perform
genetic testing on the small size of tissue specimens that are obtained
from endoscopic biopsies. This proposal will assess the ability of two
techniques to improve the detection of mutations in neoplastic tissues
using endoscopic biopsy material. The first technique is an "optical
biopsy" using laser induced fluorescence (LIF) and diffuse reflectance
spectroscopy that allows the selection the appropriate neoplastic tissue
for analysis. This device allows immediate localization of the neoplastic
tissue with a high level of accuracy, which permits the sampling of the
most appropriate tissue for molecular analysis. The samples will be
processed using a new technique termed Denaturing High Pressured Liquid
Chromatography (DHPLC) which is a rapid, sensitive, and automated
technique for screening genetic abnormalities. We would propose to test
these techniques in Barrett's esophagus, a pre-malignant epithelial tissue
of the distal esophagus. These patients have common well-characterized
molecular abnormalities that can be examined with these techniques. We
will compare the rests of molecular analysis of tissue obtained with
optical biopsy compared with obtained with standard techniques. In
addition, we will assess the ability of DHPLC followed by direct gene
sequencing to rapidly screen and identify mutations. It is anticipated
that the combination of these techniques can substantially increase the
ability to detect molecular abnormalities from limited tissue samples
obtained through endoscopy. These techniques have the potential to advance
the molecular analysis of any tissue samples of limited size.
Effective start/end date12/18/9811/30/01


  • Medicine(all)