BCIG TUTORIAL: "Molecular
pathology goes digital"
Clinical
Center (Building 10) Medical Board Room (Room 2C116)
view the seminar archive
DESCRIPTION: AQUA
(Automated Quantitative Analysis) is a recently
developed integrated fluorescent-based imaging and
analysis tool that enables the precise and simultaneous
measurement of both the subcellular localization and the
expression level of multiple proteins at different
stages of disease and within a variety of organs and
tissues. Semi-quantitative protein expression analysis
by standard chromagen-based immunohistochemical methods
(e.g. traditional ‘brown stain’ immunohistochemical
analysis) suffers from restricted dynamic ranges, semi-quantitation,
and a limited ability to multiplex markers. By utilizing
algorithms focused on molecular co-localization of
fluorophores tagged to different compartments rather
than morphometric analysis, we present data on how AQUA
provides a level of quantification equivalent to ELISA
data along with critical spatial information for
multiple markers on a single slide. The ability to apply
AQUA to tissue microarrays, whole tissue sections and
core biopsies at a range of magnifications in an
automated format has allowed extension of the platform’s
capabilities to examination of protein localization from
large compartments such as cytoplasm and nuclei, to
smaller organelles such as golgi and lysosomes.
Quantification of protein expression in multiple
molecularly-defined compartments is important for
detection of activation (such as cytoplasmic to nuclear
translocation) and allows for within-sample analysis of
the ratio of expression in these compartments in
relation to patient outcome (survival, drug response,
etc.). In addition to molecularly defined compartments
(such as DAPI to identify nuclei and pan-cadherin to
identify membranes), AQUA can be adapted to analysis of
virtual compartments. AQUA data has been shown to reveal
associations with outcome in cancer patients not
detected by semi-quantitative methods, which has
important implications in determining biomarker
associations with patient outcome as well as for
biospecific therapies. Data will be presented on the
real-world applications of this technology to cancer
patient prognosis, patient stratification, biomarker
discovery, discrimination between cancer subtypes, and
the use of this technology in integrated expression
profiling studies.
REGISTRATION: As with all BCIG
events, registration is not required. Just show up
happy.
WEBCASTING: This event will be
web cast live and be made available for post program
viewing on the BCIG web site (www.nih-bcig.org).
To get more information about our webcasting service,
please contact Meeting Master Carl Leonard by e-mail:
cleonard@lired.com
or by calling him on 301-496-0191. NIH CONTACT: Jim
DeLeo, 301-496-3848,
jdeleo@nih.gov
REFRESHMENTS: Bring refreshments
if you would like. There is an open cafeteria near the
meeting room.
BCIG WEB SITE:
www.nih-bcig.org
NIH VISITOR INFORMATION:
http://www.nih.gov/about/visitor/
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3:00 - 4:30 pm October 12, 2006
Marisa Dolled-Filhart, Ph.D.,
HistroRx
SPEAKER: Marisa Dolled-Filhart
has extensive experience with biomarker localization
and quantification in fixed tissue sections and tissue
microarrays. She was involved in pioneering work at
Yale University to apply AQUA algorithms to images
collected using fluorescent immunohistochemistry
techniques. Her work on stratification of breast
cancer patients based on biomarker profiles generated
with AQUA has been published in numerous top-tier
journals. Most recently, Dr. Dolled-Filhart was a
group leader at HistoRx, a company devoted to
developing companion diagnostics based on AQUA
technology. She is currently Technical Manager,
Business Development at HistoRx where she is
responsible for applying AQUA capabilities to projects
with pharmaceutical, academic and government partners.
Dr. Dolled-Filhart holds a Ph.D. and M.Phil. from Yale
University in Genetics, and a B.A. from Cornell
University in Biology.
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