# IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1987 · $18,728

## Abstract

The rationale for the selection of hormonal versus chemotherapy for breast
cancer patients is based on the biochemical parameter for hormone
dependency, namely the presence of cytoplasmic estrogen receptors (ER).
Tumors lacking ER and classified as hormone-independent rarely regress in
response to hormonal therapies (additive or ablative).  The frequency of
"false negatives" in this group is only 10%.  On the other hand, the
probability of misclassification of ER-positive tumors as hormone-dependent
and, therefore, as responders to hormone therapy is 40% if the presence of
ER alone is considered relevant and 30% if the presence of ER and another
hormone receptor, progesterone receptor (PR), is taken into account.  Since
ER-positive tumors are the more predominant kind (75% of all breast cancers
are ER positive) there is a need for greater accuracy in the selection of
truly hormone-dependent tumors for hormonal therapy.  In addition,
cytoplasmic ER is also a marker protein for better prognosis, late
recurrence pattern, and longer disease-free survival.  We propose to
examine the utility of classification of breast tumors based on
immunohistochemical parameters either applied individually or in
conjunction with the biochemical data on ER for more precise selection of
hormone-dependent from hormone-indifferent tumors.  Two different
approaches to immunohistochemical classification will be compared for their
relative merits:  (1)\classification based on the proportion of ER-positive
and ER-negative tumor cell population.  This will be achieved by analyzing
frozen sections from multiple areas of the tumor for the density of
ER-positive and ER-negative cells.  ER-positive cells will be identified by
immunofluorescent (IF) procedure using polyclonal antibodies specific for
Type I ER; and (2)\transportation of E2 via transformed ER to specific
nuclear acceptor sites is a prerequisite for all the molecular events
(including PR synthesis) that are dependent on estrogen.  Using
immunohistochemical procedures ER-positive tumors will be sub-classified on
the basis of the density of ER-positive cells that can translocate their
ER, in vitro, when exposed to estrogenic or antiestrogenic ligands.  An
interesting and significant observation has been the following:
Preliminary immunohistochemical studies  on 60 ER + tumors (30 PR+, 30
PR(-)) have revealed that 80% of the PR (-) tumors have an abnormality
which is expressed as an inability of in vitro translocation of ER-E2 to
the nuclear acceptor sites.  The efficacy of this mode of classification
for selecting the hormone-dependent tumors will be compared with that of
the biochemical mode of classification based on the presence/absence of PR
for selecting the hormone responders in the ER-positive group.  (2)

## Key facts

- **NIH application ID:** 3175906
- **Project number:** 3R01CA037944-03S1
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** SHANTHI RAAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $18,728
- **Award type:** 3
- **Project period:** 1984-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175906

## Citation

> US National Institutes of Health, RePORTER application 3175906, IMMUNOHISTOCHEMICAL CLASSIFICATION OF BREAST TUMORS (3R01CA037944-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175906. Licensed CC0.

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