"Luminal-AR" subtype of feline mammary carcinoma

Merial Veterinary
Scholarship
Identification of the “Luminal-AR”
“Luminal AR” subtype of feline mammary carcinoma
1. Presentation of laboratory
The research unit “AMaROC” (animal
animal cancers, models for research in comparative oncology)
oncology aims at
developing clinical studies on cancer in small companion animals (dogs and cats), the leading idea
being that cancers in cats and dogs could be excellent models of the disease in humans and fill the gap
between mouse models andd the clinical reality in humans.
Our research unit, headed by Dr Jérôme Abadie (DVM, PhD, Dipl. ECVP), gathers veterinary teachers
in internal medicine (Catherine Ibisch, Prof. Dominique Fanuel), emergency/intensive care (Françoise
Roux), medical physics (Nicolas Chouin), veterinary pathology (Frédérique Nguyen, Jérôme Abadie),
Abadie) a
hospital practitioner in small animal reproduction (Anne Gogny), a postdoctorant in nuclear imaging
(Julie Rousseau), young researchers in PhD (Floriane Morio, Laëtitia Jaillardon,
illardon, Mathieu Moreau),
Moreau 3
technicians in histopathology and a part-time
part
technician in molecular biology,, 2 part-time
part
secretaries.
Two of the scientific projects in comparative oncology conducted in AMaROC involve also physicians
and researchers in human
an medicine. These are:
• A project on canine and
nd feline mammary carcinomas conducted in collaboration with the ICO
(Integrated Center for Oncology, Nantes), particularly Prof. Mario Campone (oncologist) and Dr
Delphine Loussouarn (pathologist),
(pathologist specialists in breast cancer.
• A project on canine and feline Diffuse Large B-Cell
B Cell Lymphoma (DLBCL) conducted in
collaboration with Dr François Davodeau (researcher, INSERM),, Dr Anne Moreau (pathologist),
Prof. Steven Le Gouill (hematologist), specialists in human lymphoma.
The student will be supervised by Frédérique Nguyen (DVM, PhD, Dipl. ECVP) assistant professor
pro
in
veterinary pathology. Her/his work will be included in the project on feline mammary carcinomas, which
has been funded by Roche and the French National
Nationa Cancer Institute (INCa, Institut National du Cancer).
Cancer
List of most recent publications/communications
/communications of the laboratory related to the present project:
project
Our results were presented in international meetings in 2014:
201
Jaillardon L, Loussouarn D, Abadie J, Siliart B, Campone M, Nguyen F. Prognostic stratification of
naturally occurring Triple Negative
gative Canine invasive Mammary Carcinoma (TN-CMC)
CMC) according to IGFIGF
1R and AR expression.. Annual Meeting of the AACR (American Association
Association for Cancer Research), San
Diego, CA, USA, April 5-9,
9, 2014, poster PO.TB01.01. Model Organisms of Cancer 1.
1
Nguyen F, Besnard F, Loussouarn D, Campone M, Abadie J. Lymphatic emboli of feline invasive
mammary carcinomas: improved detection using immunohistochemistry.
i
2nd Joint European Congress
of the ESVP (European Society of Veterinary Pathology), ESTP (European Society of Toxicologic
Pathology) and ECVP (European College of Veterinary Pathologists), Berlin, Germany, August 27-30,
2
2014, oral communication O06.
Nguyen F, Valeau G,, Loussouarn D, Campone M, Abadie J. Pathologic nodal stage of feline invasive
mammary carcinomas. 2nd Joint European Congress of the ESVP, ESTP and ECVP, Berlin, Germany,
August 27-30,
30, 2014, oral communication O07.
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Merial Veterinary
Scholarship
2. Research Project
Human breast cancer is divided in subgroups with different prognoses (spontaneous evolution) and
therapeutic modalities: breast cancers (BCs) that express Estrogen Receptor alpha (ER) and/or
Progesterone Receptor (PR) are the “Luminal” BCs
BCs (relatively good prognosis, hormone-sensitive);
hormone
BCs
that overexpress HER2 (Human Epidermal Growth Factor Receptor-2)
Receptor 2) are treated with anti-HER2
anti
antibodies; BCs that are negative for ER, PR and HER2 are called “triple negative” (very poor
prognosis, no targeted
rgeted therapy available). In the triple negative subgroup however, a significant
expression of AR (Androgen Receptor) mitigates the poor prognosis and suggest that anti-AR
anti
therapies
might be beneficial; this subgroup of triple negative carcinomas is called
called “Luminal-AR”.
“Luminal
We have found
recently that canine mammary carcinomas, which are mostly of the triple negative subgroup, also
contain an AR-positive
positive subgroup (39% of cases), which could be used to validate in vivo new anti-AR
anti
therapies before their use in human oncology. We aim now at determining if feline mammary
carcinomas contain as well a “Luminal-AR”
“Luminal
subgroup.
Project title: Identification of the “Luminal-AR”
“Luminal AR” subtype of feline mammary carcinoma.
carcinoma
Aims: to assess the frequency and intensity of Androgen Receptor expression in feline invasive
mammary carcinomas; to identify the correlations between AR expression and other clinicopathological
data such as tumor stage, tumor grade, the histological type of carcinoma,
carcinoma, the presence of lymphatic
emboli. To determine the prognostic value of AR expression in female cats with invasive mammary
carcinoma. In the triple-negative
negative group, to determine if AR expression defines a “Luminal-AR”
“Luminal
subgroup
with favorable prognosis,
is, as described in human and canine triple negative mammary carcinoma.
Work program:
All of the feline cases (N=350 incl. 247 triple negative cases) have already been included in a large
retrospective cohort;; all of the protocols for immunohistochemistry have been validated.
The student is expected to
- help in finishing the collection of immunohistochemical data: automated immunohistochemistry,
interpretation of slides with the supervisor, quantitation of immunohistochemical positivity using
image analysis, data entry in the database,
database
- help in analyzing the results: correlations between AR expression and the characteristics of
feline patients and their carcinomas, assessment of the spontaneous prognosis in terms of local
recurrence, nodal and distant metastasis,
metasta
overall survival (risk of all-cause
cause death) and specific
survival (risk of cancer-related
related death),
death) using univariate (Kaplan-Meier
Meier curves, log-rank
log
tests)
and multivariate analyses (Mantel-Cox
(Mantel
models).
During his/her training period, the student will have
have the opportunity to acquire knowledge in comparative
oncology, in veterinary pathology including the principles and practice of immunohistochemistry and
quantitative image analysis, in retrospective oncology studies including the notions of relapse, overall
over
and specific survival, and in medical statistics.
Keywords: comparative oncology, mammary carcinoma,, cat, histopathology, immunohistochemistry
3. Research Environment
All of the techniques and methods necessary to completion of the project are routinely performed in our
laboratory. A resident in veterinary pathology at Oniris, Dr Elie Dagher, is also involved in this project
and supervised by F Nguyen, so potential difficulties will have been smoothened before the arrival of the
student.
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