Sabato 27 ottobre 2012 - Pacini Editore

398
Expression of rOr1 in breast cancer tissue
and synchronous lymph-node metastasis
R. Lattanzio1 , R. La Sorda1 , V. Toto2 , M. Piantelli1 , D. Angelucci3 ,
M. Iezzi2 1 Dipartimento di Scienze Biomediche, Sezione di Patologia Oncologica,
Centro Scienze dell’invecchiamento, Fondazione Università G. d’Annunzio,
Chieti; 2 Dipartimento di Medicina e Scienze dell’Invecchiamento,
Sezione di Anatomia Patologica e Medicina Molecolare, Centro Scienze
dell’invecchiamento, Fondazione Università G. d’Annunzio, Chieti;
3 U. O. di Anatomia Patologica e Citodiagnostica, Presidio Ospedaliero
“G.Bernabeo” Ortona, Centro di Riferimento Regionale per la Senologia
Introduction. Breast cancer is the most common cancer in
women worldwide 1 2 . ROR1, an orphan tyrosine kinase receptor,
is expressed in human breast cancer but not in normal breast
tissues 3 . Recently, ROR1 has emerged as a promising target
of therapy in tumors 4 . To ascertain the presence of ROR1 as
potential therapeutic target, we have analysed by immunohistochemistry
the expression of ROR1 in primary breast tumors and
in tumor/synchronous lymph-node metastasis pairs.
Material and methods. Tissue microarrays (TMA) were constructed
by extracting 2-mm diameter cores of histologically confirmed
neoplastic areas from 90 paraffin-embedded invasive primary
breast tumors and matching lymph-node metastasis (n = 21
pairs). The independent samples t-test was used to compare the
ROR1 expression in primary tumors and matched lymph-node
metastases. The SPSS (version 15.0) statistical program (SPSS
Inc., Chicago, IL) was used for analysis. The cited P value is
two-sided; P < 0.05 was considered as statistically significant.
Results. In tumor cells the expression of ROR1 was cytoplasmic
(Fig. 1). Eighty out of 90 (88.9%) tumors showed specific immunoreactivity
for ROR1, with a main percentage of positive tumor
cells of 68.6 ± 3.7SE. Twenty-one tumor/synchronous lymphnode
metastasis pairs were present in our series of 90 primitive
breast cancers. Analyzing these pairs we found that metastatic tumors,
when compared to primary ones, contained higher numbers
of neoplastic cells expressing ROR1 (P = 0.028) (Tab. I).
Fig. 1. Example of cytoplasmic expression of RoR1 in paraffin-embedded
breast cancer tissue. (Scale bar = 20_m).
Tab. I. ROR1 expression in breast cancer and matched lymph-node metastasis
(n = 21).
Mean ± SE* P °
Primary tumor 72.8 ± 6.1 0.028
Metastasis 89.8 ± 4.3
* Results are expressed as mean percent of positive tumor cells ± standard error
° independent samples t-test
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
Conclusions. As previously reported 3 , our study confirmed
that ROR1 is highly expressed in breast cancer tissues. Interestingly,
we additionally found that ROR1 is overexpressed in breast
cancer lymph-node metastases compared with primary tumors.
Although a large series are needed to further verify this result,
ROR1 has also a therapeutic potential in the treatment of breast
cancer patients with lymph-node metastasis.
references
1 Botha JL, Bray F, Sankila R, et al. Breast cancer incidence and mortality
trends in 16 European countries. Eur J Cancer 2003;39:1718-29.
2 Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in
early-stage breast cancer. Oncologist 2004;9:606-16.
3 Zhang S, Chen L, Cui B, et al. ROR1 is expressed in human breast
cancer and associated with enhanced tumor-cell growth. PLoS
One;7:e31127.
4 Yang J, Baskar S, Kwong KY, et al. Therapeutic potential and challenges
of targeting receptor tyrosine kinase ROR1 with monoclonal
antibodies in B-cell malignancies. PLoS One;6:e21018.
Chromosome 17 polysomy clinical implication in
a subset of breast cancer patients with HEr-2/neu
protein expression and negative FISH
S. Petroni1 , T. Addati1 , E. Mattioli1 , M.A. Caponio1 , M. Centrone1
, G. Mossa1 , F. Giotta2 , A. Bruno2 , G. Simone1 1 2 Anatomic Pathology Unit, Medical Oncology Department, Oncology
Institute, Bari; National Cancer Research Centre, Istituto Tumori “Giovanni
Paolo II”, Bari, Italy
Background. The HER-2 gene product, a 185 kDa receptor tyrosine
kinase, is amplified and/or overexpressed in approximately
20-25% of human breast cancers 1 2 .
The overexpressed protein is the therapeutic target for the treatment
with humanized monoclonal antibody Trastuzumab (Herceptin).
Beside HER-2 gene amplification, a subset of breast cancer
patients presents different genetic alterations, such as chromosome
17 polysomy (increased copy number of chromosome
17). Abnormalities of chromosome 17 are important molecular
genetic events in human breast cancers. The reported incidence
of chromosome 17 polysomy, as estimated by FISH, ranges from
5 to 50%. Previously published data showed that polysomy of
Chr17 may lead to HER-2 protein overexpression and that these
cases may be associated or not with HER-2 gene amplification.
Aim. We analyzed clinical behaviour in a subset of 25 polisomic
tumors which showed HER-2/neu protein expression in absence
of HER-2/neu gene amplification in FISH.
Methods: Twenty-five patient with invasive breast carcinoma
overexpressing HER-2/neu protein (Fig. 1) but without HER-2/
neu gene amplification (FISH test) (Fig. 2) were selected between
177 polisomic cases (from 2007-to 2009). Immunohistochemical
staining for estrogen (ER), progesteron (PgR) receptors and
Ki-67 (MIB-1) was performed on all cases. Follow-up data of 18
out of 25 patients were avaible. The results were recorded as the
percentage of immunoreactive cells over at least 1000 cells. Only
nuclear reactivity for ER, PgR and Ki-67 antigens was taken into
account during slide evaluation, independently of the intensity
of the staining. HER-2/neu was evaluated according to FDAapproved
scoring system.
Results. All 25 patients had diagnosis of ductal invasive breast
cancer, 18 out of 25 were grade III and 7 were grade II. Only 4 out
of 25 cases did not express ER, whereas 8 out of 25 were negative
to PgR. Regarding to MIB-1, only 3 cases showed a low kinetic
activity (cut off ≤ 20%). Three of these patients were treated
with adjuvant chemotherapy including anthracyclines followed
by trastuzumab for 52 weeks. After a median follow-up of 48
months 2 patients are disease free, while the remaining patients
relapsed on bone.
Conclusions. Conflicting results (Downey et al. Clin Cancer Res
2010;16:1281-8 and Kaufman et al. J Clin Oncol 2007;25:1009),