Biomedical Engineering Reference
In-Depth Information
f 72, C15 or f55/NUT, EDF1, ING5, KRAS, NOC3L, PPP1R5B, RRAS2,
TMPRSS2, and TPM4). The genome-wide approach could help to
evaluate the molecular determinants of sensitivity and resistance
to endocrine therapy although clinical implications of the identified
genes have yet to be tested and validated.
5.6
Diagnostic Tests for ER and PgR
In the early 1980s, the need for establishing uniformed assays
was recognized and recommended for examination through
large randomized trials conducted by the oncology cooperative
groups.
105,106
Over the past several decades, several issues on the
evaluation of hormone receptor status have been identified and
evolved. These include assay formats and methodologies, and
determinations of positive receptor status.
5.6.1
Methods for Evaluation of ER/PgR Expression
Since the 1970s, several assays with different biochemical principles,
analytic sensitivity, and analytic precision have been used for ER/
PgR evaluation. The initial assays developed were ligand-binding
assays (LBAs), which had significant limitations due to the technical
complexity, requirement for fresh-frozen tissues, high variability, and
non-specific to tumor cells.
Nonetheless, earlier randomized trials
used LBAs led to our understanding of the relationship between the
presence of ER and response to endocrine therapy. In the late 1980s,
immuno-assays using polyclonal and monoclonal antibodies to
detect ER emerged. The enzyme immunoassay (EIA) was developed
and used for quantification of ER from the cytosol extracts of fresh
tumor tissues. The amount of steroid hormone receptors detected by
EIA was highly correlated with that measured through LBAs, which
EIA was less labor-intensive.
107
108
IHC was subsequently developed
and evolved to allow detection of ER in formalin-fixed and paraffin-
embedded tissues.
It is the use of IHC method to detect the
hormone receptors in the malignant nuclei that has led to routine
and convenient evaluation of ER/PgR a practical reality.
109,110
109
With different techniques evaluating hormonal receptor status,
one of the critical issues is the assignment of cutoff values for
establishing receptor positivity. These are usually arbitrarily chosen
