22, 2006 -- 4:00 p.m. at the Fields Institute Dr.
Vladimir Iakovlev, MD, FRCPC, University Health Network
error and development of sampling strategies for biological
of relatively non-specific approaches cancer research
has moved to identification of molecular targets in
search of specific cancer treatments. Although the majority
of work is done in vitro and in animal models, final
conclusions can be drawn only after confirmation of
the findings on clinical samples. One of the major problems
is the amount of tissue used for analytical purposes.
The amount of tissue being taken from living people
is frequently limited by technical, therapeutic and
patient safety issues. Additionally, expensive and laborious
procedures limit further the size of an analyzed sample.
According to sampling theory, the major factor affecting
the sampling error is the size of a sample.
It has been shown that hypoxic (low oxygen content)
tumors are more aggressive. To further study this phenomenon,
researchers need a tool to measure the degree of hypoxia
in histological sections. A proposed marker, Carbonic
Anhydrase IX (CAIX), was plagued by controversial reports
of its correlation with direct pO2 measurements in tumors.
We analyzed multiple histological sections of biopsies
obtained from 24 patients with cervical cancer which
had parallel measurements of the oxygen tension within
the tumors. In addition RNA was extracted from the tissue
between the sections. Our data showed that CAIX protein
levels correlate well with CAIX RNA levels within the
biopsies, however they show a weak relationship with
the global tumor oxygenation status. This demonstrates
that a sampling strategy needs to be defined for each
marker before commencing a study to maximize use of
resources and increase significance of findings. The
methods of measuring protein contents in histological
sections and multiple steps contributing to the analytical
and sampling errors are explained. The questions which
need to be answered to develop sampling strategies are
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